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Lymphland International Lymphedema Online
| December 2008 - FDA Approves Drug That Boosts Stem Cell Yield For Bone Marrow Transplants The U.S. Food and Drug Administration approved Mozobil (plerixafor), a drug that helps increase the number of blood stem cells for bone marrow transplantation in patients with certain forms of blood cancer. Mozobil is intended to be used in combination with the growth factor granulocyte-colony stimulating factor (G-CSF), for treatment of adults with multiple myeloma or non-Hodgkin's lymphomas. Multiple myeloma is cancer of the plasma cell, a cell in the bone marrow that produces antibodies to help fight infection and disease. Non-Hodgkin lymphomas are a diverse group of blood cell cancers derived from lymphocytes, a type of white blood cell. Prior to receiving high-dose chemotherapy or radiation therapy, patients with these forms of cancer sometimes undergo a procedure known as apheresis in which blood stem cells are collected and stored for reinfusion after therapy. G-CSF is commonly administered to help release and collect stem cells from the bone marrow. Mozobil is an injectable drug that, when used in combination with G-CSF, boosts the number of stem cells released from the bone marrow into the blood stream. "Collecting the millions of cells needed for a bone marrow transplant can take hours or days," said Richard Pazdur, M.D., director, Office of Oncology Drug Products, Center for Drug Evaluation and Research, FDA. "Mobozil provides a new therapeutic option for patients with certain types of blood cancers by increasing the number of stem cells collected in a given time period to be reinfused after therapy." In two randomized clinical trials - one in patients with non-Hodgkin's lymphoma, the other with multiple myeloma - Mozobil combined with G-CSF increased the number of stem cells available for collection and transplantation compared with patients receiving G-CSF alone. The most commonly reported adverse reactions in these trials and other smaller studies were diarrhea, nausea, fatigue, injection site reactions, headaches, joint pain, dizziness and vomiting. Mozobil is manufactured by Genzyme Corp., Cambridge, Mass. U.S. Food and Drug Administration 26 December 2008 - BioCryst Pharmaceuticals Continues Forodesine HCl Program In Chronic Lymphocytic Leukemia BioCryst Pharmaceuticals (Nasdaq: BCRX) announced interim data from the ongoing Forodesine HCl Phase 2 program in patients with chronic lymphocytic leukemia (CLL) and data from a healthy subject pharmacokinetic and pharmacodynamic study. The CLL study will continue with an amendment to study a new dosing regimen of oral Forodesine, 200 mg twice-daily. An interim analysis was conducted on data from an exploratory Phase 2 single-arm, open-label program in patients with CLL whose previous treatment had failed. While this analysis showed that no partial or complete responses were observed, five out of 13 patients administered 200 mg of Forodesine HCl once- daily had substantial reductions in malignant lymphocytes, and at the time of the analysis, seven patients were still on study. Forodesine HCl was generally safe and well-tolerated at the 200 mg once-daily dose. In a parallel, healthy subject, pharmacokinetic and pharmacodynamic study, BioCryst compared the effect of seven days of 200 mg Forodesine HCl dosed once-daily with seven days of 200 mg Forodesine HCl dosed twice-daily. The study demonstrated substantially increased drug exposure and pharmacodynamic effect in subjects administered Forodesine HCl 200 mg twice-daily. Drug exposure, as measured by AUC, increased by 63 percent (P<0.001) for twice-daily dosing compared to once-daily dosing. Serum uric acid levels were reduced at steady state compared to baseline by 50.0 percent for twice-daily dosing compared to 23.5 percent for once-daily dosing (p<0.001), indicating increased PNP enzyme inhibition with twice- daily dosing. "The interim data demonstrates that Forodesine HCl has potential activity in patients with CLL," stated Dr. William Sheridan, BioCryst's Chief Medical Officer. "Based on these results and the normal subject pharmacokinetic and pharmacodynamic study results, we have amended the ongoing Phase 2 study, and will now administer Forodesine HCl twice-daily to examine the potential benefits of increased drug exposure. We expect to provide an update on this trial by the end of 2009." "In our experience to date, Forodesine HCl was very well tolerated by patients in this Phase 2 study. We are pleased with these results and look forward to further testing to determine the efficacy of Forodesine HCl when administered twice-daily in patients with CLL," stated Dr. Asher Chanan-Khan, Associate Professor of Oncology at Roswell Park. About CLL CLL is a disease characterized by high numbers of circulating abnormal lymphocytes (B-cells) in the peripheral blood. The disease often involves enlargement of lymph nodes in various parts of the body as well as enlargement of the spleen. CLL is the most common adult leukemia, with over 15,000 new cases per year in the United States and more than 4,000 deaths. It typically occurs in individuals between 65 and 70 years of age. CLL is not a rapidly growing cancer, but the abnormal cells accumulate in the blood, bone marrow, lymph nodes, and spleen, resulting in enlargement of these organs and decreased bone marrow and immune function. This disease interferes with the normal production of antibodies and immunoglobulins, so the body cannot properly fight infections. While therapy has improved, CLL remains incurable and patients often suffer significant infections as a consequence of the disease and treatment. About Forodesine HCl Forodesine HCl is a transition-state analog inhibitor of the target enzyme purine nucleoside phosphorylase (PNP). The drug is currently being studied in clinical trials for indications including T-cell acute lymphoblastic leukemia (T-ALL), cutaneous T-cell lymphoma (CTCL) and chronic lymphocytic leukemia (CLL). In early 2006, BioCryst entered into a strategic collaboration with Mundipharma International Holdings Limited to develop and commercialize Forodesine in markets across Europe, Asia, Australia and certain neighboring countries for use in oncology. About BioCryst BioCryst is an integrated biopharmaceutical company utilizing crystallography and structure-based drug design to develop a deep pipeline of novel therapeutics targeting major illnesses. BioCryst is currently advancing investigational new drugs discovered in-house in late-stage clinical trials for influenza and lymphoma. In addition, the Company has a pre-clinical portfolio of novel compounds, directed against infectious, cardiovascular, and autoimmune disease targets, to create long-term sustainable value. The Company's strategic alliances with the U.S. Department of Health and Human Services, Shionogi & Co., Ltd., Green Cross Corporation and Mundipharma International Holdings Ltd. validate its scientific foundation and the utility of its product candidates. For more information, please visit the Company's Web site at http://www.biocryst.com. Forward-looking statements This press release contains forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward- looking statements. Some of the factors that could affect the forward-looking statements contained herein include that our belief that many subjects in the Phase 2 clinical trials of peramivir did not receive adequate dosing by intramuscular injection may not be correct, that HHS and the Food & Drug Administration (FDA) may not agree with our analysis, that HHS may further condition, reduce or eliminate future funding of the peramivir program, that ongoing peramivir clinical trials may not be successful, that the peramivir program may not be successful, that the pivotal trial with forodesine HCl in cutaneous T-cell lymphoma (CTCL) may not meet its endpoint, that development and commercialization of forodesine HCl in CTCL may not be successful, that we or our licensees may not be able to enroll the required number of subjects in planned clinical trials of our product candidates and that such clinical trials may not be successfully completed, that BioCryst or its licensees may not commence as expected additional human clinical trials with our product candidates, that our product candidates may not receive required regulatory clearances from the FDA, that ongoing and future preclinical and clinical development may not have positive results, that we or our licensees may not be able to continue future development of our current and future development programs, that our development programs may never result in future product, license or royalty payments being received by BioCryst, that BioCryst may not be able to retain its current pharmaceutical and biotechnology partners for further development of its product candidates or it may not reach favorable agreements with potential pharmaceutical and biotechnology partners for further development of its product candidates, that our projected burn rate may not be consistent with our expectations, that BioCryst may not have sufficient cash to continue funding the development, manufacturing, marketing or distribution of its products and that additional funding, if necessary, may not be available at all or on terms acceptable to BioCryst. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst's most recent Annual Report on Form 10-K, most recent Registration Statement on Form S-3 (filed November 28, 2008), Quarterly Reports on Form 10-Q, current reports on Form 8-K which identify important factors that could cause the actual results to differ materially from those contained in the projections or forward-looking statements. BioCryst Pharmaceuticals 23 December 2008 - Lymphedema Risk For Breast Cancer Survivors Increased By Obesity Throughout the world, 10 million breast cancer survivors have a lifetime risk for developing lymphedema, a chronic condition that involves swelling of the limbs and impacts physical and psychosocial health. Second only to the recurrence of cancer, it is the most dreaded effect of breast cancer treatment. In a new study, University of Missouri researchers found that the risk of developing lymphedema is 40 percent to 60 percent higher in women with body mass index (BMI) classified as overweight or obese compared to normal weight women. The researchers recommend increased health education for breast cancer survivors. "Breast cancer survivors with high BMIs will benefit from education focused on maintaining optimal BMI and lymphedema risk reduction practices," said Jane Armer, professor in the Sinclair School of Nursing and director of nursing research at the Ellis Fischel Cancer Center. "Overweight women have the greatest risk of developing lymphedema and should be monitored closely for changes in symptoms and limb volume, especially those who have cancer treatment to the dominant side or experience post-operation swelling." Based on the analysis, lymphedema is a risk for approximately two-thirds of breast cancer survivors in the 30 months after surgery. Breast cancer survivors who develop post-op swelling have a significantly higher risk (40 percent) of developing lymphedema. According to Armer, patients with high BMIs who experience post-op swelling or were affected by cancer on their dominant side have the highest risk of developing lymphedema. MU researchers found that comparing BMI and limb volume measurements can help clinicians better detect lymphedema. "Diagnosing post-breast cancer lymphedema can be difficult because of inconsistent measurement approaches and standards of measurement reliability and validity," Armer said. "Pre-op limb volume measurement is an essential reference for post-op volume comparison and detection of post-op swelling. Clinicians should consider using a 5 percent limb volume change (LVC) approach (beyond change in BMI) as a more sensitive estimation of post-breast cancer lymphedema." ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- The study, "Post-Op Swelling and Lymphoedema Following Breast Cancer Treatment," was published in the Journal of Lymphoedema, Vol. 3, No. 2. It was co-authored by Wannapa Kay Mahamaneerat, contract research scientist for the Post-Breast Cancer Lymphedema Project at MU and former graduate research assistant in the MU Sinclair School of Nursing and Computer Science Department; Chi-Ren Shyu, director of the MU Informatics Institute; and Bob Stewart, adjunct clinical faculty in the nursing school and professor emeritus of agricultural education at MU. Source: Emily Smith University of Missouri-Columbia 23 December 2008 - FDA Submission Of Isosulfan Blue Injection ANDA Synerx Pharma, LLC announces the submission to the FDA of Isosulfan Blue Injection (generic equivalent to Lymphazurin™, Covidien (formerly US Surgical)). This ANDA submission is the culmination of a four year joint effort by Synerx Pharma, LLC and its exclusive raw material supplier Apicore, LLC. According to Synerx Pharma and Apicore, the active ingredient is extremely difficult to synthesize. Synerx Pharma stated that this product fits nicely into their Company's strategic direction; it is a difficult to produce product, serves a critical medical need, and represents an unmet market need. Lymphazurin™ has been in limited supply for a number of years, with shortages due to supply and manufacturing problems in 2001, 2002, 2006, 2007, and 2008. Synerx Pharma believes the ANDA submission, which it has already submitted, qualifies for the FDA Office of Generic Drug's GIVE (Generic Initiative for Value and Efficiency) program. This program seeks to provide an accelerated FDA review of generic products. Indications and Usage: Lymphazurin™ 1% (isosulfan blue) upon subcutaneous administration, delineates the lymphatic vessels draining the region of injection. It is an adjunct to lymphography in: primary and secondary lymphedema of the extremities; chyluria, chylous ascites or chylothorax; lymph node involvement by primary or secondary neoplasm; lymph node response to therapeutic modalities. About Synerx Pharma, LLC Synerx Pharma, LLC is a privately held corporation located in historic Bucks County Pennsylvania. Established in January 2004, the company develops and markets select pharmaceutical products aimed at meeting unmet market needs, particularly those involving some combination of barriers to entry. The company focuses on developing cost effective specialty generic pharmaceuticals and small brand products. About Apicore, LLC Apicore, LLC is a developer and manufacturer of Active Pharmaceutical Ingredients (APIs) according to current Good Manufacturing Practices (cGMPs). Based at an FDA inspected facility in Somerset, N.J., the company is committed to helping clients obtain timely approval for their ANDAs, NDAs and marketing authorizations by supplying APIs and technical support throughout the development and regulatory review process. Lymphazurin™ is a trademark of United States Surgical, a division of Tyco Healthcare Group LP. Synerx Pharma, LLC 18 December 2008 - Biopure Submits IND Application For Proposed Clinical Trial In Patients With Acute Myeloid Leukemia Biopure Corporation (Nasdaq: BPUR) announced that it has submitted to the Food and Drug Administration (FDA) an investigational new drug (IND) application to conduct a pilot phase 2 clinical trial of the company's oxygen therapeutic Hemopure(R) [hemoglobin glutamer - 250 (bovine)]. In the proposed trial Hemopure would be studied for use in the treatment of life-threatening anemia secondary to induction chemotherapy in patients with acute myeloid leukemia (AML) who refuse red blood cell transfusion. As previously reported, the company met with the FDA in July 2008 to discuss an acceptable patient population for a new clinical trial. At that time the company proposed a trial in AML patients who will not accept blood transfusions and consequently are unable to undergo potentially life-saving induction chemotherapy because of the profound anemia the chemotherapy causes. The purpose of the proposed study would be to study the efficacy of Hemopure in delivering oxygen in the absence of red blood cell transfusion. An effective treatment for this patient population represents an unmet medical need because of an expected 100% mortality within several months without induction chemotherapy. Biopure Corporation Biopure Corporation develops, manufactures and markets pharmaceuticals, called oxygen therapeutics that are intravenously administered to deliver oxygen to the body's tissues. Hemopure(R) [hemoglobin glutamer - 250 (bovine)], or HBOC-201, is approved for sale in South Africa for the treatment of surgical patients who are acutely anemic. On November 21, 2008, the Company announced that it had terminated most of its work force for financial reasons. Using its limited resources, the Company is developing Hemopure and is supporting the U.S. Navy's government-funded efforts to develop a potential out-of-hospital trauma indication. Biopure's veterinary product Oxyglobin(R) [hemoglobin glutamer - 200 (bovine)], or HBOC- 301, the only oxygen therapeutic approved for marketing by both the U.S. Food and Drug Administration and the European Commission, is indicated for the treatment of anemia in dogs. Biopure has sold more than 200,000 units of Oxyglobin since its launch. Statements in this release that are not strictly historical are forward-looking statements, including any statements implying that any proposed trial will be permitted to proceed by the FDA, that if a trial is permitted to proceed funding for the trial will be available or that if a trial is undertaken the results will be as expected. Actual results and their timing may differ materially from those projected in these forward-looking statements due to risks and uncertainties. These risks include, without limitation, uncertainties regarding the company's financial position, including its limited cash resources and need to raise additional capital to resume full operations and remain in business, unexpected costs and expenses, delays and adverse determinations by regulatory authorities, unanticipated problems with the product's commercial use, whether or not product related, and with product distributors, sales agents or other third parties, delays in clinical trials, and the other factors identified under the heading "Risk Factors" in the Company's quarterly report on Form 10-Q filed on September 15, 2008, which can be accessed in the EDGAR database at the U.S. Securities and Exchange Commission's (SEC) website, http://www.sec.gov. The company undertakes no obligation to release publicly the results of any revisions to these forward-looking statements to reflect events or circumstances arising after the date hereof. A full discussion of the company's operations and financial condition can be found in the company's filings with the SEC. Biopure Corporation http://www.biopure.com 14 December 2008 - Removal Of Pelvic Lymph Nodes Or Radiotherapy Cannot Be Recommended As Routine Treatments In Women With Early Endometrial Cancer (Astec Study) Two Articles published Online first and in an upcoming edition of The Lancet show that two common adjuvant treatments for women with early endometrial cancer - removing the pelvic lymph nodes or external beam radiotherapy - should not be part of routine care. The Articles were written by Dr Ann Marie Swart, Medical Research Council (MRC) Clinical Trials Unit, London, UK, and Professor Henry Kitchener, University of Manchester, UK, and colleagues on behalf of the ASTEC study group and the ASTEC/EN.5 writing committee. The first Article examined the benefits of removal of the pelvic lymph nodes (pelvic lymphadenectomy), in addition to the standard treatments of hysterectomy and removal of both ovaries and both fallopian tubes (bilateral salpingo-oophorectomy/BSO). Removal of the pelvic lymph nodes has been used to establish whether or not there is disease outside the uterus and is also a therapeutic procedure. In this randomised trial, the researchers analysed 1408 women from 85 centres in four countries* with endometrial cancer believed to be localised. Of these, 704 were randomly assigned to standard surgery (hysterectomy and BSO, peritoneal washing, and palpation of para-aortic nodes**; while the other 704 were assigned to standard surgery plus pelvic lymphadenectomy. The primary outcome was overall survival. The researchers found that, after a median follow-up of just over three years, 88 women in the standard surgery died compared with 103 in the lymphadenectomy group - meaning women in the lymphadenectomy group were actually 16% more likely to die in the lymphadenectomy group. When looking at the combined chances of death or recurrent disease, 144 women in the lymphadenectomy group experienced one or the other, compared with 107 in the standard group - an increased risk of 35% for women having their pelvic lymph nodes removed. The authors conclude: "This randomised trial has shown no evidence of a benefit for systematic lymphadenectomy for endometrial cancer in terms of overall, disease-specific, and recurrence-free survival. This study is one of the largest reported surgical gynaecological cancer trials...Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials." In the second Article, the effects of external beam radiotherapy (EBR) are examined. EBR has been offered to women who have had successful surgery (hysterectomy/BSO) for early endometrial cancer, but are considered to have an increased risk of recurrence due to their particular cancer pathology. This Article analyses 789 women from the ASTEC study plus a further 116 from the EN.5 study, from 112 centres in seven countries***. The patients were randomly assigned after surgery to observation (453 women) or to EBR (452). EBR was delivered in 20-25 daily fractions up to the target dose. Again the primary outcome was overall survival. The researchers found that, after a median follow-up of 58 months, 68 women in the observation group had died, compared with 67 in the EBR group. There was no evidence that overall survival was higher in the EBR group, and 5-year overall survival was 84% in both groups. When combined in a meta-analysis with other trials, these results again showed no benefit for overall survival for EBR. With brachytherapy (placement of a small radioactive pellet near to the cancer site) used in 53% of women in the trial, the local recurrence rate in the observation group at 5 years was 6%. The authors conclude: "The ASTEC/EN.5 trial has shown no evidence of a benefit for external beam radiotherapy for early endometrial cancer at intermediate or high risk of recurrence, in terms of overall, disease-specific, and disease-specific recurrence-free survival. Combining these findings with data from other trials, we can exclude even a very small benefit of radiotherapy on overall survival... Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment to improve survival for women with early endometrial cancer at intermediate or high risk of recurrence, and brachytherapy might be preferred for local control." In an accompanying Comment, Dr Michael Höckel and Dr Nadja Dornhöfer, Department of Obstetrics and Gynaecology, Women's and Children's Centre, University of Leipzig, Germany, say: "For the currently available supplementary treatments 'less may be more' for most patients with early-stage endometrial cancer and 'different may be better' for the patients with high-risk tumours." *Four countries: UK, Poland, South Africa, New Zealand **palpation= feeling of the para aortic nodes, which if abnormal would be removed, and, if found to contain cancer would mean that the patient was not eligible for the radiotherapy trial. ***Seven countries: UK, Canada, Poland, Norway, New Zealand, Australia, USA "Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study." The writing committee on behalf of the ASTEC study group The Lancet, December 13, 2008DOI:10.1016/S0140-6736(08)61766-3 Source Tony Kirby Press Officer The Lancet 32 Jamestown Road Camden London NW1 7BY http://www.thelancet.com 14 December 2008 - An Enzyme That Mutates Antibodies Also Targets A Cancer-Causing Oncogene The human immune system is in a perpetual state of self-experimentation. It expertly mutates and shuffles the DNA of its own cells to evolve new defenses against the vast array of microbes that try to invade our bodies. But when the genetic experiment goes awry, the result can be a deadly cancer. Now, Rockefeller University scientists have discovered that the same enzyme that enables the immune system's defensive creativity is also responsible for a particular genetic malfunction - a translocation of one piece of DNA to the wrong chromosome - that causes Burkitt's lymphoma. The findings, to be published in the December 12 edition of Cell, suggest the enzyme, called activation-induced deaminase (AID), is probably involved in a broader range of cancers as well. "We strongly suspect that many or all of the translocations of human lymphomas in mature B cells are the product of this enzyme," says Michel C. Nussenzweig, Sherman Fairchild Professor and head of the Laboratory of Molecular Immunology. "And there's more and more data to show that it may be involved in other cancers as well. It's been identified in stomach cancers, for instance." A very specific translocation causes Burkitt's lymphoma, a cancer that plagues children in equatorial Africa. It involves a DNA break in an immune system antibody gene and the much more rare break in a cancer- promoting gene called c-myc. Previous work had shown that AID was responsible for breaking antibody genes but not c-myc. In fact, scientists thought a host of other factors might be involved in the c-myc break, but AID had been all but ruled out. Despite the prior studies, Davide Robbiani, a research associate in Nussenzweig's lab and a Leukemia and Lymphoma Society Fellow, believed AID was the culprit. To prove it, he and his colleagues started by deleting the promoter region of the c-myc oncogene, rendering the gene inactive, in a mutant line of mice. By looking for - and not finding - the specific translocation in these mice, he showed that c-myc had to be active in order for its DNA break to take place. He then inserted a DNA tag into the mouse genome that allowed him to induce a break at the c-myc gene, which occurs only very rarely if left to its own devices. He found that his artificially created breaks were comparable in most every way to the breaks caused by AID, but when he looked for the translocation in mice that didn't produce this enzyme, they were nowhere to be found. "This is a definitive study," says Nussenzweig, who is also a Howard Hughes Medical Institute investigator. "We now know AID is causing damage in other parts of the genome, not just in antibody genes." Because AID normally enables the genetic experimentation that's critical to an effective immune response, shutting it down even to fight cancer is perilous. "As a general rule, you wouldn't want to give an AID inhibitor to everyone because immune systems would not be working so well," Nussenzweig says. Still, a pharmaceutical AID inhibitor, if developed, might prove useful in treating certain tumors that are expressions of this powerful gene mutator. The next step is to figure out exactly how AID works and identify other genetic sites where AID is active. "We are now developing the tools to do exactly that," Robbiani says. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- Source: Brett Norman Rockefeller University 12 December 2008 - Researchers Identify Key Mechanism That Occurs At The Inception Point Of Many Human Lymphomas Researchers at the Keck School of Medicine of the University of Southern California (USC) have explained how certain key mutations occur in human lymphomas a process that has, until now, remained a mystery. The findings of the study, published in the Dec. 12 issue of the journal Cell, will have a significant impact on future study of how human lymphoma occurs. Chromosomal translocations, in which segments of DNA are moved around the genome, are DNA mutations frequently found in blood cancers. They occur when two chromosomes break and the resulting fragments are reassembled in an exchange, says Michael R. Lieber, M.D/Ph.D., Rita and Edward Polusky Professor in Basic Cancer Research at the Keck School of Medicine and the study's principal investigator. "Our study provides new insight into understanding how these translocations occur and describes a key and informative fingerprint at these chromosomal break sites," Lieber says. The fingerprint had been overlooked for decades because chromosomal break sites typically suffer damage that obscures the fingerprint, he says. "The precise steps leading to this pathologic rearrangement process especially how the DNA is broken have been a mystery for 25 years, in large part because these events occur long before the cancer becomes clinically apparent, and conventional experimental techniques do not reflect the process as it occurs naturally," says Albert Tsai, M.D/ Ph.D. candidate at the Keck School of Medicine and the lead author of the study. Expanding on previous work done at the Keck School and USC Norris Comprehensive Cancer Center and elsewhere, researchers studied patient tumor chromosomal translocations to gain an important clue as to how the most common lymphomas are caused. The study demonstrated that these breaks are focused at CpG sites, short special sequences in the genome, within restricted breakage zones. The CpG localization occurs in early B-cells, but not in translocations before or after that stage. Their findings implicated roles for two enzymes AID and RAG complex which are normally present in lymphocytes and that function to diversify the immune system to defend against attack by bacteria, viruses and parasites, Lieber says. The diversification process involves altering the DNA which encodes antibodies, by cutting and rejoining the DNA in a way that sometimes goes awry. This appears to be what causes the chromosomal translocations, he says. "Based on previous clues, we did a number of biochemical studies to verify our hunch about the mechanism of translocation," Lieber says. "Our study demonstrates the biochemical feasibility of the sequence of events proposed, and this matches the fingerprint left by the chromosomal translocations." The study relied on an important collaboration with Chih-Lin Hsieh, Ph.D., Catherine & Joseph Aresty Chair in Urologic Research at the Keck School of Medicine, and Markus Muschen, M.D., associate professor of pediatrics, biochemistry and molecular biology at the Keck School and director of the Leukemia Research Program at Childrens Hospital Los Angeles. The study was funded by the National Cancer Institute and the National Institute of General Medical Sciences. Albert G. Tsai, Haihui Lu, Sathees C. Raghavan, Markus Muschen, Chih-Lin Hsieh and Michael R. Lieber. "Human Chromosomal Translocations at CpG Sites and a Theoretical Basis for their Lineage and Stage Specificity." Cell. D-08-00489R3. University of Southern California Health Sciences 1975 Zonal Ave., #400 Los Angeles CA 90033 United States http:// www.usc.edu/hsc --- 11 December 2008 - Promising Results From Two Trials Highlighting Developmental Oral IMiDS® Compound Pomalidomide Presented At ASH Meeting Celgene International Sàrl (Nasdaq: CELG) today announced that its next IMiDs compound, pomalidomide, has shown promising activity with manageable safety and tolerability for the treatment of relapsed/refractory multiple myeloma (MM) and myelofibrosis. The data were presented at the 50th Annual American Society of Hematology meeting in San Francisco, CA. Early analysis of the Phase II MM study, in which half of the 60 patients with relapsed MM received combined low-dose dexamethasone with pomalidomide, showed that 76 percent of the patients experienced disease improvement or stabilization. Another key finding showed a 29 percent response rate among patients who previously did not respond to REVLIMID® therapy. Objective response was achieved by 58 percent of patients. Eight of the 60 patients had dose reductions. The most commonly occurring major adverse events were neutropenia (32%), thrombocytopenia (3%) and anemia (3%). Investigators concluded that for most patients, pomalidomide plus low-dose dexamethasone was generally well tolerated with manageable adverse events. However, there was one patient death due to pneumonia while neutropenic in this refractory, pre-treated population. The study's conclusion was that pomalidomide was highly active in this segment of multiple myeloma patients. The second Phase II trial, evaluating 84 patients with advanced myelofibrosis with myeloid metaplasia, was a four-arm blinded adaptive design trial. The study evaluated two different doses of pomalidomide with or without prednisone, with a prednisone-only arm as a control. All but one patient had failed prior therapies. The Grade 2 or greater side effects were infrequent and comparable to the prednisone control except for thrombocytopenia that was experienced in one of 22 patients and one of 19 patients treated with 2 mg of pomalidomide with or without prednisone. Thirty-five percent of the treated pomalidomide patients experienced blood cell transfusion independence. At the time of this presentation, 15 of the 16 responders remain in remission. Granulocytopenia and normal spleen size correlated with response, but the percent of abnormal cytogenetics and the presence of a JAK2 mutation did not. "The interest in our next IMiDs compound, pomalidomide, by the hematological community was demonstrated by both clinical abstracts being selected for oral presentations at the annual meeting of the American Society of Hematology," stated Jerome B. Zeldis, Chief Medical Officer, Celgene Corporation. "Based on these findings and others, Celgene will be developing pomalidomide for relapsed multiple myeloma and other hematological conditions." About Pomalidomide Pomalidomide is an IMiDs® compound, a member of a proprietary group of novel immunomodulatory agents. These immunomodulatory agents, taken orally, have unique multiple mechanisms of action that involve the microenvironment of the cancer cell, not just the malignant cell itself. The IMiDs pipeline is covered by a comprehensive intellectual property estate of issued and pending patent applications in the US, EU and other regions. About Multiple Myeloma Multiple myeloma is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. Most patients with multiple myeloma, however, have cells that produce a form of immunoglobulin called paraprotein (or M protein), which does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease remains unknown. About Myelofibrosis Myelofibrosis with myeloid dysplasia is often referred to as a chronic form of leukemia. It is a serious bone marrow disorder that begins in stem cells that form blood cells. Too few red cells are produced with an overproduction of white cells and platelets. That in turn results in a buildup of collagen in the bone marrow cavity, causing extensive scarring. The results are anemia, fatigue and susceptibility to infection. About Celgene International Sàrl Celgene International Sàrl, located in Boudry, in the Canton of Neuchâtel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website at http://www.celgene.com. This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company's filings with the Securities and Exchange Commission such as Form 10-K, 10-Q and 8-K reports. Celgene International Sàrl View drug information on Revlimid. 11 December 2008 - Group In Lymphoma Research Chooses Revlimid For Study In Disease's Largest Patient Population Celgene International Sarl (Nasdaq: CELG) and the Groupe d'Etude des Lymphomes de l'Adulte (GELA) today announced the initiation of an international randomized, double-blind, controlled Phase III study to evaluate the therapeutic potential of REVLIMID (lenalidomide) as a maintenance therapy for elderly, high- risk patients with diffuse large B-cell lymphoma (DLBCL) who have responded to standard first line Rituximab, Cyclophosphamide, Doxorubicin, Oncovin and Prednisolone (R-CHOP). Currently, there is no approved therapy proven to maintain remission after induction with R-CHOP therapy in patients with DLBCL. GELA is the leading Cooperative Group in the world for studying the treatment of adult lymphoma patients, and its work has helped establish the standard of care in the treatment of DLBCL, as well as other lymphoma histologies. "Response rates seen to date are quite encouraging with REVLIMID monotherapy in heavily pretreated patients across a variety of lymphoma subtypes," said lead study investigator Professor Bertrand Coiffier, Head of the Department of Hematology, Hospices Civils de Lyon, France. "The response rates observed with REVLIMID combined with its unique profile as an oral, immunotherapeutic cancer agent provide the potential to significantly prolong the survival of these patients through a maintenance regimen." This study, in which REVLIMID will be tested as an agent to prevent relapse after initial therapy, aims to advance the treatment of patients diagnosed with DLBCL, an aggressive form of non-Hodgkin's lymphoma (NHL). DLBCL is the most commonly diagnosed subtype of NHL with approximately 35,000 new cases diagnosed per year in the US and Europe. Most patients who relapse after initial treatment with standard chemotherapy tend to have a poor prognosis for long-term survival. The clinical benefits of REVLIMID, as a single agent in heavily pretreated patients across various histological subtypes of NHL, including DLBCL, continue to be reported in peer-reviewed publications and at major international medical meetings. "We are excited that a premier research cooperative group, such as GELA, that has the resources and experience to choose any drug for its study, selected REVLIMID as the innovative therapy to advance treatment options for patients in need with aggressive lymphomas." said Jean Pierre Bizarri, M.D., Head of Global Clinical Oncology/Hematology for Celgene Corporation. In this trial designed to enroll 621 patients, REVLIMID® will be administered daily three out of four weeks for 24 months (26 cycles) in patients responding to R-CHOP. Patients are expected to have received at least six cycles of R-CHOP regimens and up to eight cycles of R-CHOP repeated every two or three weeks according to local protocol. The primary objective of the study is to determine progression-free survival associated with REVLIMID maintenance compared to placebo in responding elderly patients with DLBCL treated in the first line with R-CHOP. The secondary objectives are to assess the percentage of patients who convert from partial response to complete response; the efficacy according to the response to R-CHOP; and the overall survival in both groups of patients, as well as safety. REVLIMID is currently approved in the European Union, United States, Canada, Argentina and Switzerland in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy and in Australia in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy. REVLIMID is also approved in Canada, the United States and Argentina for transfusion-dependent anemia due to low- or intermediate-1- risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. REVLIMID has obtained Orphan Drug designation in the EU, U.S., Switzerland, Australia and Japan. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- About REVLIMID REVLIMID is an IMiDs® compound, a member of a proprietary group of novel immunomodulatory agents. REVLIMID and other IMiDs compounds continue to be evaluated in over 100 clinical trials in a broad range of oncological conditions, both in blood cancers and solid tumors. The IMiDs pipeline is covered by a comprehensive intellectual property estate of U.S. and foreign issued and pending patent applications including composition-of-matter and use patents. About Non-Hodgkin's Lymphoma Approximately 1.5 million people worldwide are living with various forms of lymphoma, and it is estimated that 300,000 people die each year. In terms of incidence and death, NHL is the second fastest growing cancer in the United States and the third fastest growing in the rest of the world. Lymphoma is the name for the group of blood cancers that start in the lymphatic system, which is part of the body's immune system. Lymphomas generally start in the lymph nodes or lymphatic tissue in sites of the body such as the stomach or intestines. They may involve the marrow and the blood in some cases as well. Most people with lymphoma have one of the many different kinds of NHL. Lymphomas generally are classified into two equal groups: half are indolent (low-grade) lymphomas while the remaining are aggressive (intermediate/high-grade). Intermediate/high-grade lymphomas spread rapidly, and left untreated, can be fatal within six months to two years. Diffuse large B-cell lymphoma is the most common of the non-Hodgkin lymphomas, accounting for up to 30 percent of newly diagnosed cases. Diffuse large B-cell lymphoma is an aggressive, or fast-growing lymphoma. It can arise in lymph nodes or outside of the lymphatic system, in the gastrointestinal tract, testes, thyroid, skin, breast, bone or brain. Often, the first sign of diffuse large B-cell lymphoma is a painless or even painful rapid swelling in the neck, armpit or groin caused by enlarged lymph nodes. Other symptoms include night sweats, unexplained fevers and weight loss. About GELA The Groupe d'Etude des Lymphomes de l'Adulte (GELA), created in 1984 and headquartered in Lyon, France, is the largest cancer Cooperative Group devoted to adult lymphomas, with a fully integrated clinical research sister organisation (GELARC), around 500 members and more than 100 institutions throughout France, Belgium, Luxemburg, Switzerland and Portugal contributing to its studies. So far, these centers have included more than 25,000 patients in GELA's trials, which have been instrumental in improving adult lymphomas diagnostic and therapeutic approaches. For more information, please visit the group's website at http://www.gelarc.org. About Celgene International Sarl Celgene International Sarl, located in Boudry, in the Canton of Neuchatel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website at http://www.celgene.com/. REVLIMID® and IMiDs® are registered trademarks of Celgene Corporation. This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company's filings with the Securities and Exchange Commission such as 10K, 10Q and 8K reports. Source: Kevin Loth Celgene International Sàrl 11 December 2008 - Revlimid Data In Multiple Myeloma Reports 3-Year Survival Rates In Phase III ECOG E4AO3 Study Celgene International Sarl (Nasdaq:CELG) has announced more mature data from clinical studies of REVLIMID (lenalidomide) in newly-diagnosed multiple myeloma, presented at a joint symposium of the American Society of Clinical Oncology (ASCO) and the American Society of Hematology (ASH). The results from the ECOG E4A03 study of REVLIMID plus low-dose dexamethasone (Rd) versus REVLIMID plus a standard dose of dexamethasone (RD) in newly diagnosed multiple myeloma patients detailed some of the highest three-year overall survival rates ever reported in the intent to treat population. These results showed a three-year survival rate of 75 percent in the RD arm of the study and 74 percent in the Rd arm. Additionally, in a Landmark Analysis where patients were treated continuously with Rd therapy as opposed to stem cell transplant, patients achieved an overall response rate of 91 percent with a 57 percent complete response plus very good partial response rate (CR + VGPR). Grade 3 or higher non-hematologic toxicities in the RD vs. Rd arms of the study included deep vein thrombosis (DVT)/pulmonary embolism (PE) (26% vs. 12%) infection/pneumonia (16% vs. 9%) cardiac ischemia (3% vs. 0.5%) and neuropathy (2% in both arms). "These further data from the E4A03 study reinforce our view that REVLIMID plus low-dose dexamethasone has high activity and is well-tolerated long-term therapy in newly diagnosed multiple myeloma," said Mohamad Hussein, M.D., Vice President, Medical Affairs, Hematology for Celgene. "Additionally, the impressive data from the Landmark Analysis underscores the need to treat continually to control residual disease and improve outcomes." REVLIMID is currently approved in the European Union, United States, Canada, Argentina and Switzerland in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy and in Australia in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy. REVLIMID is also approved in Canada, the United States and Argentina for transfusion-dependent anemia due to low- or intermediate-1- risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. REVLIMID has obtained Orphan Drug designation in the EU, U.S., Switzerland and Australia and Japan. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- About REVLIMID® REVLIMID is an IMiDs® compound, a member of a proprietary group of novel immunomodulatory agents. REVLIMID and other IMiDs compounds continue to be evaluated in over 100 clinical trials in a broad range of oncological conditions, both in blood cancers and solid tumors. The IMiDs pipeline is covered by a comprehensive intellectual property estate of U.S. and foreign issued and pending patent applications including composition-of- matter and use patents. About Multiple Myeloma Multiple myeloma (also known as myeloma or plasma cell myeloma) is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. However, most patients with multiple myeloma have cells that produce a form of immunoglobulin called paraprotein (or M protein) that does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease remains unknown. About Celgene International Sarl Celgene International Sarl, located in Boudry, in the Canton of Neuchatel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company's filings with the Securities and Exchange Commission such as Form 10-K, 10-Q and 8-K reports. Source: Kevin Loth Celgene International Sàrl 11 December 2008 - Promising Results From 2 Trials Highlighting Pomalidomide Presented At ASH Celgene International Sarl (Nasdaq: CELG) has announced that its next IMiDs compound, pomalidomide, has shown promising activity with manageable safety and tolerability for the treatment of relapsed/refractory multiple myeloma (MM) and myelofibrosis. The data were presented at the 50th Annual American Society of Hematology meeting in San Francisco, CA. Early analysis of the Phase II MM study, in which half of the 60 patients with relapsed MM received combined low-dose dexamethasone with pomalidomide, showed that 76 percent of the patients experienced disease improvement or stabilization. Another key finding showed a 29 percent response rate among patients who previously did not respond to REVLIMID® therapy. Objective response was achieved by 58 percent of patients. Eight of the 60 patients had dose reductions. The most commonly occurring major adverse events were neutropenia (32%), thrombocytopenia (3%) and anemia (3%). Investigators concluded that for most patients, pomalidomide plus low-dose dexamethasone was generally well tolerated with manageable adverse events. However, there was one patient death due to pneumonia while neutropenic in this refractory, pre-treated population. The study's conclusion was that pomalidomide was highly active in this segment of multiple myeloma patients. The second Phase II trial, evaluating 84 patients with advanced myelofibrosis with myeloid metaplasia, was a four-arm blinded adaptive design trial. The study evaluated two different doses of pomalidomide with or without prednisone, with a prednisone-only arm as a control. All but one patient had failed prior therapies. The Grade 2 or greater side effects were infrequent and comparable to the prednisone control except for thrombocytopenia that was experienced in one of 22 patients and one of 19 patients treated with 2 mg of pomalidomide with or without prednisone. Thirty-five percent of the treated pomalidomide patients experienced blood cell transfusion independence. At the time of this presentation, 15 of the 16 responders remain in remission. Granulocytopenia and normal spleen size correlated with response, but the percent of abnormal cytogenetics and the presence of a JAK2 mutation did not. "The interest in our next IMiDs compound, pomalidomide, by the hematological community was demonstrated by both clinical abstracts being selected for oral presentations at the annual meeting of the American Society of Hematology," stated Jerome B. Zeldis, Chief Medical Officer, Celgene Corporation. "Based on these findings and others, Celgene will be developing pomalidomide for relapsed multiple myeloma and other hematological conditions." ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- About Pomalidomide Pomalidomide is an IMiDs® compound, a member of a proprietary group of novel immunomodulatory agents. These immunomodulatory agents, taken orally, have unique multiple mechanisms of action that involve the microenvironment of the cancer cell, not just the malignant cell itself. The IMiDs pipeline is covered by a comprehensive intellectual property estate of issued and pending patent applications in the US, EU and other regions. About Multiple Myeloma Multiple myeloma is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. Most patients with multiple myeloma, however, have cells that produce a form of immunoglobulin called paraprotein (or M protein), which does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease remains unknown. About Myelofibrosis Myelofibrosis with myeloid dysplasia is often referred to as a chronic form of leukemia. It is a serious bone marrow disorder that begins in stem cells that form blood cells. Too few red cells are produced with an overproduction of white cells and platelets. That in turn results in a buildup of collagen in the bone marrow cavity, causing extensive scarring. The results are anemia, fatigue and susceptibility to infection. About Celgene International Sarl Celgene International Sarl, located in Boudry, in the Canton of Neuchatel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company's filings with the Securities and Exchange Commission such as Form 10-K, 10-Q and 8-K reports. Source: Kevin Loth Celgene International Sàrl 11 December 2008 - Prolonged Overall Survival For Patients With Acute Myeloid Leukemia Demonstrated By Data The Myelodysplastic Syndromes (MDS) Foundation have announced that data presented at this year's American Society of Hematology (ASH) Meeting in San Francisco demonstrate that patients with acute myeloid leukemia (AML) who were treated with VIDAZA (azacitidine) had significantly increased overall survival compared to those treated with conventional care regimens (CCR). AML is a cancer of myeloid blood cells where abnormal cells accumulate in the bone marrow and interfere with normal blood cell production. Patients with AML typically have a poor prognosis and do not respond well to conventional chemotherapy. Roughly 30 percent of patients diagnosed with MDS will progress to AML. Dr. Pierre Fenaux, of the University of Paris, presented the updated results from an international phase III trial (AZA-001) which was the first study to show an increased overall survival for higher-risk MDS patients. One-third of patients enrolled in the trial met the World Health Organization (WHO) criteria for AML. This analysis showed that 50 percent of the AML patients who were treated with VIDAZA survived at least two years, compared to only 16 percent of patients treated with CCR. "The data presented at this year's ASH Meeting are encouraging for both physicians and patients and demonstrate the major advancements that have been made in treating hematologic conditions, like MDS and AML, over the past several years," said Kathy Heptinstall, Operating Director of the Myelodysplastic Syndromes Foundation, "We are hopeful about the potential of novel therapies, like VIDAZA, which are helping patients to live longer with a better quality of life." The data presented today are a follow-up to results from the AZA-001 trial presented at the American Society of Clinical Oncology Meeting in June, which showed that patients with high-risk MDS who received VIDAZA had higher one-year survival rates in all response categories, including partial remission, stable disease and hematologic improvement, compared to those who received CCR without necessarily achieving complete remission. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- About MDS MDS is a cancer in which the bone marrow fails to make enough functioning blood cells, either red blood cells, white blood cells or platelets. It is not known exactly how many people have MDS, however, about 20,000 to 25,000 new cases are diagnosed annually in the U.S. In addition, roughly 30 percent of patients diagnosed with MDS will progress to acute myeloid leukemia (AML). About the MDS Foundation The Myelodysplastic Syndromes Foundation, Inc. is a multi-disciplinary, international organization devoted to the prevention, treatment, and study of the myelodysplastic syndromes. The organization is based upon the premise that international cooperation will accelerate the process leading to the control and cure of these diseases. For further information, please visit http://www.mds-foundation.org. Source: Kathy Heptinstall MDS Foundation View drug information on Vidaza. 11 December 2008 - Alfacell's ONCONASE(R) And R-Amphinase Show Anti-Tumor Activity In Chronic Lymphocytic Leukemia And Acute Myeloblastic Leukemia Cells Alfacell Corporation (Nasdaq: ACEL) announced that American Society of Hematology (ASH) annual meeting abstracts in Blood (2008 112: Abstract 4205 & 2008 112: Abstract 4010) report that ONCONASE (ranpirnase) and R-Amphinase (R-Amph) show anti-tumor activity in chronic lymphocytic leukemia (CLL) and acute myeloblastic leukemia (AML) cells alone as well as in combination with standard chemotherapeutic agents, expanding the spectrum of malignancies for which Alfacell's proprietary ribonucleases show promising activity. The abstracts are the result of research conducted by collaborators at the Department of Hematology, Medical University of Lodz in Poland, Alfacell and the Brander Cancer Research Institute and Department of Pathology at New York Medical College. ONCONASE and R-Amph are amphibian endoribonucleases with unique mechanisms of inhibiting the growth and causing apoptosis (programmed cell death) of malignant cells. Previously, ONCONASE has been shown to affect multiple cellular pathways involved in these mechanisms, and has been validated in many solid tumor cell lines, as well as a T-cell leukemia cell line. These reports now broaden ONCONASE's activity into CLL and AML, and include a related endoribonuclease, R-Amph. For the study in CLL, leukemic cells were isolated from 36 untreated patients with CLL and were cultured for 24-72 hours with either ONCONASE or R-Amph alone and in combination with the purine analogues cladribine (2-CdA) and fludarabine (FA), as well as with doxorubicin. A significant cytotoxic effect of ONCONASE and R-Amph was evident after 48 and 72 hours of treatment, respectively. Synergistic activity was seen in the combination of the endonuclease plus either purine analogue. The combination of doxorubicin with ONCONASE or R-Amph demonstrated an increase in pro-apoptotic activity when compared to single agent treatment, although the effect was not statistically significant. This is the first study showing cytotoxic, pro-apoptotic effects of ONCONASE and R-Amph in CLL, and synergism with the most widely used CLL therapies. For the study in AML, leukemic cells isolated from 22 patients with newly diagnosed AML were cultured for 24-72 hours with either ONCONASE or R-Amph alone and in combination with doxorubicin or cytarabine arabinoside. In these experiments, both endoribonucleases showed significant activity against AML cells. The main mechanism of this action was shown to be the triggering of caspase-dependent apoptosis by activation of the mitochondrial pathway. The combination of ONCONASE or R-Amph with doxorubicin in AML exhibited significant synergistic cytotoxicity, and offers insights into the potential therapeutic enhancement for doxorubicin, from a class of drugs commonly used as first line therapy in AML. "These ex vivo studies expand the potential of ONCONASE as a potential treatment for various leukemias," said Kuslima Shogen, Alfacell's chief executive officer. "Based on our knowledge of the impact of ONCONASE on cellular pathways involved in tumor cell growth, and also in resistance to chemotherapy, additional studies may further demonstrate ONCONASE's promising anti-leukemic activity." About AML AML (acute myeloblastic leukemia) is a cancer of the myeloid line of white blood cells, characterized by the rapid proliferation of abnormal cells which accumulate in the bone marrow and interfere with the production of normal blood cells. AML is a potentially curable disease; but only a minority of patients are cured with current therapy. AML is treated initially with chemotherapy aimed at inducing a remission; some patients may go on to receive a hematopoietic stem cell transplant. Although cure rates have been reported to be 20- 45%, this is likely to be much lower for elderly patients and those who cannot tolerate aggressive therapy. About CLL CLL(chronic lymphocytic leukemia) is a cancer of the lymphocytic line of white blood cells. CLL affects a particular lymphocyte, the B cell, which originates in the bone marrow, develops in the lymph nodes, and normally fights infection. In CLL, the DNA of a B cell is damaged, so that it can't fight infection, but it grows out of control and crowds out the healthy blood cells that can fight infection. While generally considered incurable, CLL progresses slowly in most cases. Determining when to start treatment and by what means is often difficult. In addition, several drugs are used to treat CLL, however Fludarabine is the most extensively studied and is currently the most commonly used first-line therapy in this disease. About ONCONASE(R) ONCONASE is a first-in-class therapeutic product candidate based on Alfacell's proprietary ribonuclease (RNase) technology. A natural protein isolated from the leopard frog, ONCONASE has been shown in the laboratory and clinic to target cancer cells while sparing normal cells. ONCONASE triggers apoptosis, the natural death of cells, via multiple molecular mechanisms of action. Alfacell has licensed the U.S. commercial rights for ONCONASE to Strativa Pharmaceuticals, a division of Par Pharmaceutical, Inc. Strategic marketing and distribution agreements for ONCONASE have been secured with Megapharm Ltd. for Israel, BL&H Co. Ltd. for Korea, Taiwan and Hong Kong, USP Pharma Spolka Z.O.O., an affiliate of US Pharmacia, for Eastern Europe, and GENESIS Pharma, S.A. for Southeastern Europe. ONCONASE has been granted fast track status and orphan-drug designation for the treatment of malignant mesothelioma by the FDA. Additionally, ONCONASE has been granted orphan-drug designation in the European Union and Australia. About Alfacell Corporation Alfacell Corporation is the first company to advance a biopharmaceutical product candidate that works in a manner similar to RNA interference (RNAi) through late-stage clinical trials. The product candidate, ONCONASE, is an RNase that overcomes the challenges of targeting RNA for therapeutic purposes while enabling the development of a new class of targeted therapies for cancer and other life-threatening diseases. For more information, visit http://www.alfacell.com. Safe Harbor This press release includes statements that may constitute "forward-looking" statements, usually containing the words "believe," "estimate," "project," "expect" or similar expressions. Forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from the forward-looking statements. Factors that would cause or contribute to such differences include, but are not limited to, uncertainty whether the clinical trial results will allow the company to complete submission of a New Drug Application and if a New Drug Application submission is completed, uncertainty whether FDA will file or approve such application, uncertainties involved in transitioning from concept to product, uncertainties involving the ability of the company to finance research and development activities, potential challenges to or violations of patents, uncertainties regarding the outcome of clinical trials or differences of opinion in interpreting the results of clinical trials, the company's ability to secure necessary approvals from regulatory agencies, dependence upon third-party vendors, and other risks discussed in the company's periodic filings with the Securities and Exchange Commission. By making these forward-looking statements, the company undertakes no obligation to update these statements for revisions or changes after the date of this release. Alfacell Corporation http://www.alfacell.com 10 December 2008 - ZIOPHARM Presents Positive Darinaparsin Phase II Data At ASH Meeting ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) announced today that on December 6th it presented positive data from a Phase II study of darinaparsin (ZinaparTM) for the treatment of advanced lymphomas at the 50th American Society of Hematology (ASH) Annual Meeting held in San Francisco, CA. The ongoing Phase II study demonstrates that darinaparsin is clinically active in heavily pretreated, relapsed/refractory patients with lymphoma. Of 15 evaluable patients, 4 patients (27%) had objective responses (Complete Response + Partial Response) and 3 patients (20%) had stable disease. Of 4 evaluable patients with refractory peripheral T-cell lymphoma, 1 achieved a complete response and 2 had stable disease. One patient with marginal zone lymphoma and 1 with marginal zone lymphoma transformed to diffuse large B-cell lymphoma achieved partial responses. Of the 4 patients with relapsed/refractory Hodgkin's disease 1 achieved partial response and 1 had stable disease. The medium number of prior regimens of chemotherapy was 3; in addition 6 patients received prior radiation and 7 patients had previously undergone bone marrow transplantation. Darinaparsin was very well tolerated with possibly related adverse events including nausea/vomiting, fatigue/weakness and dizziness. The absence of bone marrow suppression in these heavily pretreated patients, together with activity suggest that this new drug will be easily combinable in treatment. "These data indicate darinaparsin is active in lymphoma," stated Michael Craig M.D., Professor and Director of Blood and Marrow Transplantation of West Virginia University and a lead investigator of the study. "The drug is remarkably well tolerated and easily combinable for therapy. We look forward to further developing it in lymphoma." About ZIOPHARM Oncology, Inc. ZIOPHARM Oncology is a biopharmaceutical company engaged in the development and commercialization of a diverse portfolio of cancer drugs. The Company is currently focused on three clinical programs. Palifosfamide (ZymafosTM or ZIO-201) is a novel molecule that is the functional active metabolite of ifosfamide, a standard of care for treating sarcoma, testicular and other cancers. Palifosfamide delivers only the cancer fighting component of ifosfamide. It is expected to overcome the resistance of ifosfamide and cyclophosphamide in certain cancers. It does not have the toxic metabolites of ifosfamide that cause the debilitating side effects of "fuzzy brain" (encephalopathy) and severe bladder inflammation. Intravenous (IV) palifosfamide is currently in a Phase II randomized trial to treat soft tissue sarcoma. An oral form of palifosfamide has been developed preclinically and is expected to enter clinical study in 2009. Indibulin (ZybulinTM or ZIO-301) is a novel, oral tubulin binding agent that targets both mitosis and cancer cell migration. Indibulin is expected to have several potential benefits, including oral dosing, application in multi-drug resistant tumors, no neuropathy and minimal overall toxicity. Indibulin has shown early activity in Phase I study as a single agent in many types of solid tumors. Indibulin is also currently in the Phase I portion of Phase I/II trials in combination with Tarceva® and Xeloda®. Preclinical study continues with both dose density and metronomic administration. Darinaparsin (ZinaparTM or ZIO-101) is a novel organic arsenic being developed for the treatment of various hematologic and solid cancers. Preclinical and Phase I and II results to date demonstrate that darinaparsin is much less toxic than other forms of arsenic. Intravenous darinaparsin continues to be studied in a Phase II hematology trial with favorable treatment activity in certain lymphomas and in Phase I study with oral administration. Darinaparsin has been well tolerated in all trials to date. ZIOPHARM's operations are located in Boston, MA with an executive office in New York. Further information about ZIOPHARM may be found at http://www.ziopharm.com. Forward-Looking Safe Harbor Statement This press release contains forward-looking statements for ZIOPHARM Oncology, Inc. that involve risks and uncertainties that could cause the Company's actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions that are subject to risks and uncertainties, which could cause actual outcomes and results to differ materially from these statements. Among other things, there can be no assurance that any of the Company's development efforts relating to its product candidates will be successful, or such product candidates will be successfully commercialized. Other risks that affect forward- looking information contained in this press release include the possibility of being unable to obtain regulatory approval of the Company's product candidates, the risk that the results of clinical trials may not support the Company's claims, and risks related to the Company's ability to protect its intellectual property and its reliance on third parties to develop its product candidates. The Company assumes no obligation to update these forward-looking statements, except as required by law. ZIOPHARM 10 December 2008 - Dangerous Side Effect For Lymphoma Patients Prevented By New Therapy Patients respond well to a new three-drug combination for indolent B cell lymphoma that also spares them prolonged, potentially lethal, suppression of blood production in the bone marrow, researchers at The University of Texas M. D. Anderson Cancer Center reported at the 50th annual meeting of the American Society of Hematology. Pentostatin, cyclophosphamide and rituximab together are providing the same remission rate as other combinations but with minimal long-term bone marrow suppression, said study presenter Felipe Samaniego, M.D., associate professor in M. D. Anderson's Department of Lymphoma and Melanoma. Myelosuppression leads to production of fewer red blood cells, white blood cells and platelets. When prolonged, it can lead to myelodysplastic syndrome, which comprises several conditions that cause potentially lethal insufficient blood production. "The worst outcome of long-term myelosuppression for indolent B cell lymphoma patients is myelodysplastic syndrome," Samaniego said. "In this study, out of 80 patients, none developed MDS." And 77 of 80 (96 percent) experienced either complete remission or unconfirmed complete remission. Some did have low blood counts, but all were short-term. Overall, the combination is well-tolerated, the research team reported. Prolonged myelosuppression also makes treatment much more difficult if a patient's lymphoma recurs, Samaniego said. "Patients treated with myelosuppressing agents have a difficult time tolerating another round of chemotherapy if their lymphoma comes back." Indolent B cell lymphomas comprise follicular lymphoma, small lymphocytic lymphoma, and marginal zone lymphoma. These slow-growing but potentially lethal cancers are the most common form of non-Hodgkin lymphoma. Samaniego and colleagues have been testing new drug combinations against indolent B cell lymphoma that reduce myelosuppression. Two years ago, a combination of fludarabine, mitoxantrone and dexamethasone with rituximab and interferon alpha reduced the incidence of MDS to 4 percent of patients, down from a historical rate of around 10 percent. The key ingredient in pushing the MDS rate to zero, Samaniego says, was substitution of fludarabine with pentostatin. Both are nucleoside analogs, which interfere with DNA reproduction, and target lymphoid cells, making them attractive drugs for lymphomas. Earlier research indicated that pentostatin is less toxic to bone marrow than other members of this drug class. "The PCR combination is a very promising therapy for indolent B cell lymphoma," Samaniego said. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- Co-authors with Samaniego are Michelle Fanale, M.D., Barbara Pro, M.D., F.B. Hagemeister, M.D., Peter McLaughlin, M.D., Jorge Romaguera, M.D., Sattva Neelapu, M.D., Maria Anna Rodriguez, M.D., Luis Fayad, M.D., Anas Younes, M.D., and Larry Kwak, M.D., Ph.D., all of the Department of Lymphoma and Myeloma. About M. D. Anderson The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For six of the past nine years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report. Source: Scott Merville University of Texas M. D. Anderson Cancer Center 10 December 2008 - Intense Chemotherapy Wards Off Recurrence In Half Of Mantle Cell Lymphoma Patients After Seven Years More than half of younger mantle cell lymphoma patients who received an intensive regimen of chemotherapy as frontline treatment remain in remission seven years later, researchers at The University of Texas M. D. Anderson Cancer Center reported at the 50th annual meeting of the American Society of Hematology. Among patients 65 or younger, 52 percent survived without disease recurrence at a median of seven years of follow-up, said first author Jorge Romaguera, M.D., professor in M. D. Anderson's Department of Lymphoma and Myeloma. Overall survival for this subgroup was 68 percent. "There is some disagreement about whether these younger patients should receive a bone marrow transplant as frontline therapy rather than chemotherapy," Romaguera said. "Our results with chemotherapy are as good as any transplant data. We don't believe a transplant is necessary as a first treatment in newly diagnosed mantle cell lymphoma." Mantle cell lymphoma is one of the most lethal versions of non-Hodgkin lymphoma. Romaguera and colleagues have followed 97 patients for up to nine years who received rituximab plus a combination of chemotherapies known as hyperCVAD, alternated with rituximab plus high-dose methotrexate/cytarabine in 6-8 cycles. Out of those patients, 87 percent achieved either a complete response or unconfirmed complete response after six cycles. Of 65 patients who were 65 or younger, 30 relapsed. Of 32 patients older than 65, a total of 23 relapsed. Overall survival for the entire group, including all ages up to 80 years, was 60 percent; 43 percent were at failure-free survival, with no recurrence of the disease, at seven years of median follow-up. Survival is about the same for patients who undergo stem cell transplantation, Romaguera said. No randomized studies between the chemotherapy regimen, stem cell transplants or the chemotherapy plus stem cell transplant have been done. About 3,500 new cases of mantle cell lymphoma are diagnosed in the United States annually. The average age of diagnosis is the mid-sixties and median survival is about four years. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- The ongoing research is funded by the Getz Family Fund for Mantle Cell Lymphoma Research, the Rich Family Fund for Lymphoma Research and the Lowell and Rebecca Whitlock Fund for Mantle Cell Lymphoma Research. Co-authors with Romaguera are Luis Fayad, M.D., Alma Rodriguez, M.D., Fredrick Hagemeister, M.D., Barbara Pro, M.D., Peter McLaughlin, M.D., Anas Younes, M.D., Felipe Samaniego, M.D., Jatin Shah, M. D., Kim Hartig, Fernando Cabanillas, M.D., Larry Kwak, M.D., Ph.D. and Michael Wang, M.D., all of M. D. Anderson's Department of Lymphoma and Myeloma; and Hagop Kantarjian, M.D., of the Department of Leukemia. About M. D. Anderson The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For six of the past nine years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report. Source: Scott Merville University of Texas M. D. Anderson Cancer Center 10 December 2008 - Multiple Myeloma: New Data On ZOLINZA (Vorinostat) In Combination With Bortezomib Results from two Phase 1 studies of ZOLINZA® (vorinostat), Merck's oral histone deacetylase (HDAC) inhibitor, administered in combination with bortezomib, showed early anti-tumor activity in patients with relapsed and/or refractory multiple myeloma, including those previously treated with and no longer responding to bortezomib. Results of these studies, which were designed primarily to determine the maximum tolerated dose of the combination regimen, were presented at the 50th Annual Meeting of the American Society of Hematology (Abstract #871). ZOLINZA is approved in the United States for treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. The findings presented are investigational. "Based on these data, Merck has moved rapidly into late-stage clinical development to further evaluate ZOLINZA in combination with bortezomib for advanced multiple myeloma," said Jose Garcia-Vargas, M. D., senior director, Clinical Oncology, Merck Research Laboratories. "This action affirms our belief in the potential of ZOLINZA and our commitment to improve the lives of patients living with this devastating disease." Merck has initiated global, multi-center trials investigating ZOLINZA in combination with bortezomib in patients with relapsed and/or refractory multiple myeloma. These trials, part of the VANTAGE (Vorinostat Clinical Trials in Hematologic and Solid Malignancies) program, include a Phase 3 randomized, double- blind, placebo-controlled trial and an open-label Phase 2b trial, both of which are now recruiting patients. "Patients with advanced multiple myeloma eventually relapse and that makes identification of new drugs a greater imperative," said Sundar Jagannath, M.D., lead investigator of the Phase 3 study and chief, Multiple Myeloma Program, St. Vincent's Comprehensive Cancer Center in New York City. "These trials will help us better understand the potential of ZOLINZA combined with bortezomib in myeloma treatment, and we are grateful to the patients who will participate." Phase 1 study details The first Phase 1 trial, led by Donna Weber, M.D., University of Texas, M.D. Anderson Cancer Center, was a multi-center open-label, escalating-dose study of 34 patients with relapsed/refractory multiple myeloma, 33 of whom were available for evaluation of response. Patients were administered oral ZOLINZA 200 mg bid or 400 mg daily for 14 days and bortezomib 0.7 or 0.9 mg/m2 I.V. on days 1, 4, 8, 11 and 15 or bortezomib 0.9, 1.1 or 1.3 mg/m2 I.V. on days 1, 4, 8 and 11. Cycles were repeated every 21 days for < 8 cycles until progressive disease or intolerable toxicity. Patients who did not experience disease progression and continued to meet eligibility criteria after the first 8 cycles, were allowed to continue with the combination regimen at the same dose and schedule. The study's primary objective, determining the maximum tolerated dose (MTD), was not achieved because two or more dose-limiting toxicities (DLTs) did not occur at any dose level. However, the maximum administered dose was ZOLINZA 400 mg daily for 14 days plus 1.3 mg/m2 bortezomib. In the assessment of activity as measured by European Blood and Marrow Transplantation Group (EBMT) criteria, 54 percent of patients experienced either a partial response (36 percent, n=12) or a minimal response (18 percent, n=6). Thirty-nine percent (n=13) demonstrated stable disease and six percent (n=2) experienced progressive disease. Among seven evaluable patients who were previously treated with and were refractory to bortezomib, a response rate of 4/7 (57 percent) was observed: two had a partial response, two had a minimal response and three had stable disease. Two patients at differing dose levels experienced a DLT (transient AST elevation and thrombocytopenia). The most common adverse events (>20 percent) were nausea (n=21), diarrhea (n=20), thrombocytopenia (n=17), vomiting (n=17), fatigue (n=14), constipation (n=8) and increased lacrimation (excess secretion of tears, n=8). The second Phase 1 study, led by Ashraf Badros, M.D., University of Maryland, and sponsored by the National Cancer Institute under a Clinical Trials Agreement with Merck for vorinostat and a Cooperative Research and Development Agreement with Millennium for bortezomib, enrolled 23 patients with relapsed or refractory multiple myeloma, 21 of whom were available for objective response evaluation. Patients received ZOLINZA (100 mg bid, 200 mg bid, 400 mg daily or 500 mg daily) on days 4-11 in combination with bortezomib (1.0 or 1.3 mg/m2 I.V.) on days 1, 4, 8 and 11. Cycles were repeated every 21 days for < 8 cycles. If no response was observed at cycle 2, dexamethasone 20 mg was added on days 4-8. MTD, the primary objective, was achieved at ZOLINZA 400 mg daily on days 4-11 and bortezomib 1.3 mg/m2 I.V. on days 1, 4, 8 and 11. Assessment of clinical activity, a secondary objective, showed 10 percent (n=2) achieved a very good partial response, 33 percent (n=7) achieved a partial response, 48 percent (n=10) showed stable disease and 10 percent (n=2) experienced progressive disease to the combination regimen. Among eight evaluable patients who were previously treated with and were refractory to bortezomib, a response rate of 3/8 (38 percent) was observed: three had a partial response and four had stable disease. Dexamethasone was added at cycle 2 for six patients with progressive disease, at cycle 4 in five patients, and at cycle 6 in two patients. Two patients in the 500 mg group experienced DLTs (fatigue and prolonged QT interval). Pharmacokinetics of ZOLINZA were not altered by the addition of bortezomib. The main side effects observed were hematologic; Grade 3/4 side effects included anemia (n=6), neutropenia (n=5), thrombocytopenia (n=19), diarrhea (n=4), fatigue (n=6), prolonged QTc (n=1), hyponatremia (n=4) and hypokalemia (n=4). VANTAGE multiple myeloma trials VANTAGE 088: The randomized, placebo-controlled Phase 3 trial will enroll 742 patients at more than 35 centers across the United States, Latin America, Europe, Asia/Pacific, Middle East and Africa. Eligible patients must be 18 years or older, have a diagnosis of multiple myeloma, and have received at least one but no more than three prior treatment regimens. Patients who have previously received bortezomib therapy must have experienced a complete, partial or minimal response and not be considered refractory to bortezomib. The study will compare progression-free survival in patients taking bortezomib with either ZOLINZA or placebo. Overall survival, time to progression, objective response and tolerability also will be assessed. VANTAGE 095: The open-label Phase 2b study is anticipated to enroll 142 patients at more than 13 sites in North America, Europe, Asia, and Middle East. To qualify, patients must be at least 18 years or older, have a diagnosis of multiple myeloma, and have had at least two prior courses of treatment. In addition, patients must be refractory to bortezomib taken alone or in combination with other anti-myeloma therapies and have been exposed to prior immunologic therapies, such as thalidomide or lenalidomide. The study will assess the objective response rate as well as progression-free survival, overall survival, time to disease progression and tolerability. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- To learn more about the VANTAGE clinical trial program, including the studies of ZOLINZA in advanced multiple myeloma, visit http://www.merckcancertrials.com. About multiple myeloma Multiple myeloma is a cancer of the blood plasma cell and the second most common blood cancer after non- Hodgkins lymphoma. More than 56,000 Americans are living with this disease, which occurs more frequently in men than women. The average age at diagnosis is approximately 60 years for both men and women. According to the American Cancer Society, the number of adults diagnosed with multiple myeloma is increasing, with more than 19,960 new cases anticipated to be diagnosed this year. Multiple myeloma is treatable but not curable. About ZOLINZA ZOLINZA works by inhibiting the enzymatic activity of HDAC1, HDAC2, HDAC3 (Class 1) and HDAC 6 (Class II) at nanomolar concentrations (IC50<86nM). In some cancer cells, excess amounts of the enzyme HDAC prevent the activation of genes that control normal cell activity. Based on in vitro studies, ZOLINZA is believed to decrease the activity of HDAC. Decreasing the activity of HDAC allows for the activation of genes that may help to slow or stop the growth of cancer cells. The exact mechanism of the anticancer effect of ZOLINZA has not been fully characterized. Important safety information about ZOLINZA As pulmonary embolism and deep vein thrombosis have been reported as adverse reactions, physicians should be alert to the signs and symptoms of these events, particularly in patients with a prior history of thromboembolic events. Treatment with ZOLINZA can cause dose-related thrombocytopenia and anemia. If platelet counts and/or hemoglobin are reduced during treatment with ZOLINZA, the dose should be modified or discontinued. Gastrointestinal disturbances, including nausea, vomiting and diarrhea, have been reported and may require the use of antiemetic and antidiarrheal medications. Fluid and electrolytes should be replaced to prevent dehydration. Pre-existing nausea, vomiting and diarrhea should be adequately controlled before beginning therapy with ZOLINZA. Hyperglycemia has been observed in patients receiving ZOLINZA. Serum glucose should be monitored, especially in diabetic or potentially diabetic patients receiving ZOLINZA. Adjustment of diet and/or glucose therapy may be necessary. QTc prolongation has been observed. Monitor electrolytes and ECGs at baseline and periodically during treatment. Administer with caution in patients who have or may develop QTc prolongation. Hypokalemia or hypomagnesemia should be corrected prior to administration with ZOLINZA. The most common adverse events observed in clinical trials with ZOLINZA for CTCL, regardless of causality, were fatigue (52 percent), diarrhea (52 percent), nausea (41 percent), dysgeusia (28 percent), thrombocytopenia (26 percent), anorexia (24 percent), decreased weight (21 percent) and muscle spasm (20 percent). About Merck Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate its medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. Forward-Looking Statement This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Forward- looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2007 and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference. Prescribing information and patient product information for ZOLINZA® are attached and are also available at http://www.zolinza.com. Source: Eva Boratto Merck & Co. 10 December 2008 - Celator(R) Pharmaceuticals Presents Phase 1 Results With CPX-351 In Patients With Advanced Leukemia At The American Society Of Hematology Meeting Celator Pharmaceuticals announced that a Phase 1 dose escalating study of CPX-351 (cytarabine: daunorubicin) Liposome Injection established the recommended dose for Phase 2 studies and confirmed preliminary observations of safety, enhanced pharmacokinetics and promising anti-tumor activity in patients with advanced leukemia. A final analysis of the Phase 1 data (abstract #2984) and supportive findings from a pre-clinical pharmacodynamic model (abstract #942) were presented at the 50th American Society of Hematology (ASH) Annual Meeting in San Francisco. "In the Phase 1 trial, CPX-351 had a tolerability profile that appears better than conventional cytarabine/daunorubicin treatment and produced impressive anti-leukemic responses, including complete remissions (CRs) at and below the maximum tolerated dose, in relapsed and refractory patients," said Eric J. Feldman, MD, of the Weill Medical College of Cornell University and New York-Presbyterian Hospital, the principal investigator in the study. "These encouraging results suggest that CPX-351 may offer advantages to conventional administration of these commonly used drugs. We are excited to participate in the two Phase 2 studies." In the study, complete remissions were observed in 11 of 47 patients, including 10 patients (9 CRs and 1 CRp - complete remission without full platelet recovery) of 44 with AML and 1 patient of 3 with acute lymphocytic leukemia (ALL) following treatment with CPX-351. Of the 10 AML CRs, 7 occurred at the two highest dose levels, although complete remissions were achieved at dose levels as little as one third of the maximum tolerated dose (MTD). Of note, 7 CRs were achieved in 22 patients in the 1st salvage setting (patients in first relapse or with refractory disease) and 3 CRs were achieved in 22 patients in the 2nd or greater salvage settings. In addition, CRs were observed in patients older than 70 years, in those with complex cytogenetic abnormalities, and in patients with prior cytarabine/anthracycline treatment. "The standard of care for AML hasn't changed in 30 years and there is an urgent need to improve treatment for both newly diagnosed and relapsed patients," said Arthur Louie, MD, chief medical officer at Celator Pharmaceuticals. "We began enrolling patients in a Phase 2 study in newly diagnosed, elderly patients with AML and we expect to start enrollment soon in a Phase 2 study in patients with AML in first relapse." CPX-351 represents a new approach to developing drug combinations in which drug molar ratios with synergistic anti-tumor activity are encapsulated in a drug delivery vehicle and the desired ratio is maintained following administration using Celator's proprietary CombiPlex(R) technology platform. CPX-351 has been granted orphan drug status by the U.S. Food & Drug Administration for the treatment of AML. "CPX-351 incorporates two of the most active agents against AML in a manner that, as we've shown in this study, maintains ratio-dependent synergy after administration," said Scott Jackson, chief executive officer, Celator Pharmaceuticals. "We believe this unique capability has the potential to improve treatment outcomes for patients and we are looking to our randomized Phase 2 trials for proof of this principle." The safety profile of CPX-351 observed in the study was considered favorable. The most frequent and severe adverse events were those related to potential or documented infections including fever, febrile neutropenia, bacteremia, pneumonia and sepsis, common occurrences in the treatment of patients with AML. Although, mortality related to treatment is normally an issue when treating AML patients, there were no deaths within 7 days of treatment and 6 deaths (13%) within 30 days of receiving CPX-351. The induction mortality seen in the Phase 1 study was deemed encouraging by investigators. Major GI toxicity was uncommon with only 4 patients experiencing grade 3 or greater nausea and vomiting or mucositis. Pharmacokinetic data collected during the study confirmed the bioavailability of cytarabine and daunorubicin, demonstrated a prolonged half-life for both drugs and their metabolites, and confirmed that the synergistic ratio was maintained for more than 24 hours after infusion. The Phase 1 study enrolled 37 patients with advanced AML, secondary AML and ALL, during the dose- escalation phase. The maximum tolerated dose was established at 101 units/m2. An additional 10 patients were recruited and treated at this dose level to confirm tolerability and collect preliminary data on efficacy, bringing the total trial enrollment to 47. The recommended dose for Phase 2 study was determined to be 101 units/m2 given as a 90 minute infusion on treatment days 1, 3, and 5. These findings were supported by a separate pre-clinical study that was also reported at the ASH meeting. Using a bone marrow engrafted human leukemia xenograft model, investigators compared CPX-351 with conventional cytarabine/daunorubicin treatment. The study confirmed that CPX-351, unlike the conventional combination, produced prolonged exposure of CPX-351 in the bone marrow and evidence of direct uptake of CPX-351 by leukemia cells with subsequent intracellular release of the drugs. Exposure of leukemic cells to synergistic drug ratios was confirmed. In November, Celator announced enrollment of the first patient in a randomized Phase 2 study of CPX-351 versus conventional cytarabine and daunorubicin ("7 + 3") in patients with newly diagnosed AML, between 60 and 76 years of age. A second Phase 2 study of CPX-351 in patients 18-60 years old with AML in first relapse is also being initiated. About Acute Myeloid Leukemia (AML) The National Cancer Institute defines AML as a quickly progressing disease in which too many immature white blood cells (not lymphocytes) are found in the blood and bone marrow. In 2008, the American Cancer Society's Cancer Facts and Figures estimates 13,290 new cases of AML and 8,820 deaths. About Celator Celator(R) Pharmaceuticals, Inc., with locations in Princeton, NJ, and Vancouver, BC, is a privately held pharmaceutical company developing new and more effective therapies to treat cancer. CombiPlex(R), the company's drug ratio technology platform, represents a novel approach that identifies molar ratios of drugs that will deliver a synergistic benefit, locks the desired ratio in a drug delivery vehicle that maintains the ratio in patients with the goal of improving clinical outcomes. The company pipeline includes: CPX-1 (a liposomal formulation of irinotecan:floxuridine), currently in Phase 2 in patients with colorectal cancer; CPX-351 (a liposomal formulation of cytarabine:daunorubicin), currently in Phase 2 in patients with acute myeloid leukemia; CPX-571 (a liposomal formulation of irinotecan:cisplatin), a preclinical stage compound; and multiple research programs. Based on the applications of CombiPlex, Celator is positioned to advance a broad pipeline of combination therapies involving both previously approved and novel drug agents. For more information, please visit the company's website at www.celatorpharma.com. List of abstracts: ASH Abstract # 942 Mayer L, Wahseng L, Dos Santos N, et al. Synergistic cytarabine:daunorubicin ratios delivered by CPX- 351 to human leukemia xenografts is associated with liposome-mediated bone marrow drug accumulation, intracellular delivery of encapsulated agents to leukemia cells, and increase efficacy. Poster presented Saturday, December 6, 2008. ASH Abstract # 2984 Feldman EJ, Lancet J, Kolitz EJ, et al. Phase 1 study of a liposomal carrier (CPX-351) containing a synergistic, fixed molar ratio of cytarabine (Ara-C) and daunorubicin (DNR) in advanced leukemias. Poster presented Monday, December 8, 2008. Celator Pharmaceuticals http://www.celatorpharma.com 10 December 2008 - Three Studies Presented At The American Society Of Hematology Annual Meeting Showed Response To Treatment With Campath(R) Bayer HealthCare Pharmaceuticals Inc. announced results from three studies showing that treatment with Campath(R) (alemtuzumab) showed activity in high-risk chronic lymphocytic leukemia (CLL) patients who have poor prognostic indicators. These findings were presented at the 50th Annual Meeting of the American Society of Hematology in San Francisco, California. Treatment for CLL can be complicated by genetic risk factors. In some cases of CLL, at least one of the 23 pairs of chromosomes in a cell is found to be either deleted or part of it is lost. One deletion that is occasionally seen in CLL patients is the loss of the short arm of chromosome 17 (17p deletion), which may indicate a poor prognosis including significantly inferior survival compared to other CLL patients. Past studies have shown that treatment naive CLL patients were less likely to have 17p deletions than previously treated patients with CLL, indicating that cytogenetic abnormalities may be acquired during the course of treatment. Effective CLL therapies for patients with 17p deletion are limited. In one analysis of high-risk patients (abstract #3164), authors used the largest database available on the efficacy of Campath monotherapy to conduct a retrospective analysis of Campath treatment in 138 patients with advanced CLL, stratified according to cytogenetics. Of these patients, 33 percent had the 17p deleted cytogenetic abnormality. Campath administration was found to provide an overall response rate [ORR; complete response rate (CRR) + partial response rate (PRR)] of 38 percent in the total cohort, and an ORR of 44 percent in patients with 17p deletion. Additionally, in patients with 17p deletion, treatment with Campath resulted in progression free survival (PFS) and overall survival (OS) of 7.1 months and 19.1 months, respectively. "Data show that some people with CLL who have 17p abnormalities may have poor outcomes and may not respond as well to standard chemotherapeutic agents," said lead investigator Michael Fiegl, MD, Department of Internal Medicine, Academic Natters Hospital, Natters, Austria. "This analysis showed activity in patients across all cytogenetic categories -- including high risk patients with 17p deletion and in patients where conventional chemotherapy has failed. The results of this analysis warrant further prospective, clinical studies in patients with 17p deletion." A second study (abstract #2095) evaluated a combination of cyclophosphamide, fludarabine, alemtuzumab (Campath) and rituximab (CFAR) as a frontline therapy in high-risk CLL patients. Of the 48 patients evaluated in this ongoing trial, 28 percent had 17p deletion. In the total cohort, treatment with the CFAR regimen resulted in an ORR of 94 percent and a CRR of 69 percent. In patients with 17p deletion, treatment with the CFAR regimen resulted in an ORR of 77 percent and a CRR of 54 percent. "Patients with 17p deletion who have active disease and need treatment are at high risk for lower complete and overall remission rate, shorter progression-free and overall survival," said lead investigator William G. Wierda, MD, PhD, assistant professor of medicine, M.D. Anderson Cancer Center, Houston, Texas. "In this analysis, Campath in combination with the FCR regimen showed activity in previously untreated patients with 17p deletion. The CFAR regimen may be a viable first-line therapy for patients in this population, although further study is warranted." In a third multicenter study (abstract #329) of 103 CLL patients who were fludarabine refractory, unfavorable genetics were frequent (17p deletion: 29 percent, 11q deletion: 19 percent, unmutated IgVH: 68 percent, TP53 mutation: 34 percent). In this study, patients received doses of Campath three times per week. After a median follow-up time of 37.9 months, the study found an ORR of 34 percent, a CRR of four percent, and a PRR of 30 percent among the total patient population. Median PFS time was 7.7 months, and median OS time was 19.1 months. "These analyses are an important step forward in the consideration of targeted therapies for treating high-risk CLL," said Pam Cyrus, vice president, Medical Affairs, Oncology, Bayer HealthCare Pharmaceuticals. "We remain committed to determining the best treatment regimen for all patients with CLL, including this high-risk patient population." CLL is characterized by the accumulation of functionally immature white blood cells (lymphocytes) in the bone marrow, blood, lymph tissue and other organs. Roughly 90,000 people in the United States are living with CLL, according to the Leukemia and Lymphoma Society. More people are living with CLL than any other type of leukemia, and most people with CLL are at least 50 years old. About the Studies Abstract #3164 Clinical Outcome of B-Cell Chronic Lymphocytic Leukemia Following Alemtuzumab Therapy: Retrospective Study within Various Cytogenetic Risk Categories Using the largest database of efficacy analysis of Campath in CLL, researchers identified 138 CLL patients (73 male, 65 female, with a median age of 64 years) stratified according to cytogenetic markers that were identified by fluorescent in situ hybridization (FISH) testing. The median number of two prior therapies in this group was two (range, 0 - 10), and of the patients who received prior treatment with fludarabine (n=113), 70 percent were refractory to the fludarabine treatment, 25 percent sensitive, and in five percent this was unknown. Responses were evaluated according to the National Cancer Institute (NCI) criteria, and researchers also assessed PFS and OS. Patients had a variety of cytogenetic abnormalities, including: 17p deletion (33 percent), 13q deletion (14 percent), trisomy 12 (12 percent), 11q deletion (20 percent) and 22 percent without any of the aforementioned abnormalities. The ORR was 38 percent, with a 44 percent ORR in the 17p deletion group, 53 percent in patients with 13q deletion, 56 percent in the trisomy 12 group and 21 percent in the 11q deletion group. Patients without any of these abnormalities had an ORR of 27 percent. Median PFS and OS for the whole group were 6.9 months and 30 months, respectively. In 17p deletion, patients' PFS was 7.1 months and OS was 19.1 months. A subanalysis of patients with 17p deletion who were also resistant to fludarabine (n=25), showed ORR of 28 percent and PFS and OS rates of 7.2 and 19.1 months, respectively. These results did not differ from those in fludarabine resistant patients categorized as having good risk cytogenetics. Abstract #2095 CFAR, An Active Frontline Regimen for High-Risk Patients with CLL, Including Those with Del 17p In this analysis, researchers evaluated Campath in combination with the standard treatment regimen known as FCR (fludarabine, cyclophosphamide and rituximab) as front-line therapy to a high-risk group of CLL patients. Of the 60 patients intended for analysis in the CFAR group, 48 were evaluated for response and follow-up at the time of this interim analysis. Within this group of 48 patients, 28 percent (n=13) had 17p deletion identified by FISH analysis prior to treatment. Treatment with Campath resulted in an ORR of 94 percent and a CRR of 69 percent. In patients with 17p deletion, treatment with Campath resulted in an ORR of 77 percent and a CRR of 54 percent. CFAR treatment regimen was associated with more myelosuppression and fewer patients in this group could receive all six of the intended courses compared with an historic high-risk group treated with FCR. There was no significant difference in incidence of infection during treatment with CFAR compared to FCR, with the exception of cytomegalovirus (CMV) reactivation. Follow-up continues for the patients treated on this trial to evaluate responses in all 60 enrolled patients and time-to-event endpoints. Abstract #329 Subcutaneous Alemtuzumab (Campath) in Fludarabine-Refractory CLL: Final Results of the CLL2H Trial of the GCLLSG and Comprehensive Analysis of Prognostic Markers The multicenter trial evaluated subcutaneous alemtuzumab given three times weekly at 30 mg in fludarabine refractory CLL. From September 2002 to February 2006, 103 patients were enrolled and received at least one dose of alemtuzumab. Median age was 63 years. Subcutaneous treatment was performed on an outpatient basis in 96 percent of patients and had to be temporarily interrupted in 65 patients due to neutropenia (27 percent), anemia (three percent), thrombocytopenia (eight percent), infections (36 percent), and was stopped early in 65 cases due to insufficient response (43 percent), hematotoxicity (14 percent) and infections (29 percent). The median alemtuzumab dose given was 722 (3-2203) mg. Toxicity observed during the treatment period was mostly grade 1/2 apart from hematotoxicity. Grade 3/4 neutropenia, thrombocytopenia, and anemia occurred in 56 percent, 57 percent, and 50 percent of patients, respectively. Grade 3/4 non-CMV infection occurred in 29 percent. CMV reactivation was observed in 15 percent total. Grade 3/4 occurred in eight percent of patients. All CMV episodes were successfully treated with anti-CMV therapy, and there was no CMV-related death. Injection site reactions occurred in 34 percent of patients and were grade 1 or 2 except in one patient who had a grade 3 reaction. After a median follow-up time of 37.9 months, there were 75 deaths, 56 percent due to disease progression, 31 percent due to infection, and 13 percent unrelated to CLL. ORR was 34 percent (CRR four percent, PRR 30 percent), median PFS time was 7.7 months, and median OS time was 19.1 months. About Chronic Lymphocytic Leukemia CLL is the most prevalent form of leukemia in adults. The disease is most commonly diagnosed among people age 50 or older and is characterized by the accumulation of functionally immature white blood cells (lymphocytes) in the bone marrow, blood, lymph tissue and other organs. Two types of lymphocytes are present in the blood, B cells and T cells. The majority of this patient population (90 percent) suffers from a subtype called B-cell chronic lymphocytic leukemia, or B-CLL. Symptoms include fatigue, bone pain, excessive sweating, abnormal bruising, and decreased appetite and weight loss. Bone marrow infiltration leads to a lack of healthy blood cells, thus leading to fatigue, susceptibility to bleeding and weakening of the immune system, exposing the patient to a higher risk of infection. About Cytogenetic Markers In some cases of CLL, at least one of the 23 pairs of chromosomes on a cell is found to be either deleted or part of it is lost. The most commonly seen deletions involve parts of chromosomes 13, 11 and 17. The loss of part of chromosome 13 is usually linked with a slower growing disease and a better outlook, while defects in chromosomes 11 or 17 often indicate a poorer outlook. Cytogenetic testing evaluates chromosomes under a microscope to detect any of these abnormalities. FISH is a type of cytogenetic test that uses special fluorescent dyes that only attach to specific parts of particular chromosomes. It can be used on regular blood or bone marrow samples and is very accurate, which is why this test is now used in many medical centers. Additional abstracts examining Campath in high-risk CLL patients presented at ASH showed comparable results. About Campath Campath was the first monoclonal antibody approved by the United States Food and Drug Administration (FDA) for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). In September 2007, the FDA approved a supplemental Biologics License Application (sBLA) for Campath and granted regular approval for Campath as a single-agent for the treatment of B-CLL. Campath was initially approved in 2001 under accelerated approval regulations for the treatment of B-CLL in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Campath was developed by Genzyme Corporation. Campath is marketed in the U.S. by Bayer HealthCare Pharmaceuticals Inc., as Campath, and outside the United States as MabCampath(R). Important Safety Information WARNING: CYTOPENIAS, INFUSION REACTIONS, AND INFECTIONS -- Cytopenias: Serious, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia can occur in patients receiving Campath. Single doses of Campath greater than 30mg or cumulative doses greater than 90mg per week increase the incidence of pancytopenia. -- Infusion Reactions: Campath administration can result in serious, including fatal, infusion reactions. Carefully monitor patients during infusions and withhold Campath for Grade 3 or 4 infusion reactions. Gradually escalate Campath to the recommended dose at the initiation of therapy and after interruption of therapy for 7 or more days. -- Infections: Serious, including fatal, bacterial, viral, fungal, and protozoan infections can occur in patients receiving Campath. Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus infections. Campath is indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). Campath is administered as an IV infusion over two hours and should be dose escalated to recommended dose of 30 mg/day three times per week for 12 weeks. Patients are premedicated with oral antihistamine and acetaminophen prior to dosing. The most commonly reported adverse reactions are infusion reactions (fever, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), and infections (CMV viremia, CMV infection, other infections). In clinical trials, the frequency of infusion reactions was highest in the first week of treatment. Other commonly reported adverse reactions include vomiting, abdominal pain, insomnia and anxiety. The most commonly reported serious adverse reactions are cytopenias, infusion reactions, and immunosuppression/infections. See "Warnings and Precautions," and "Adverse Reactions" sections of full Prescribing Information. About Bayer HealthCare Pharmaceuticals Inc. Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals operation of Bayer HealthCare, an affiliate of Bayer AG. One of the world's leading, innovative companies in the healthcare and medical products industry, Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the United States, Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, General Medicine, Hematology/Neurology, and Oncology. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases. About Genzyme One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start- up to a diversified enterprise with more than 10,000 employees in locations spanning the globe and reported revenues in 2007 of $3.8 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation. With many established products and services helping patients in nearly 90 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as immune disease, infectious disease, and other areas of unmet medical need. Forward Looking Statements This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our annual and interim reports to the Frankfurt Stock Exchange and in our reports filed with the U.S. Securities and Exchange Commission (including our Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. Bayer HealthCare Pharmaceuticals Inc. http://www.campath.com View drug information on Campath. 09 December 2008 - Study Finds Statins Do Not Interfere With Rituximab Treatment For Lymphomas Statins, drugs widely prescribed to lower cholesterol, do not interfere with a commonly used medication to treat lymphomas, according to a Mayo Clinic study presented at the 50th Annual Meeting of the American Society of Hematology (http://www.hematology.org/meetings/2008/) in San Francisco. In fact, statins may slow the progression of certain types of lymphoma. The study focused on the impact of statin use on outcomes of patients with two most common lymphoma types, diffuse large B-cell lymphoma and follicular lymphoma. Both are cancers of the immune system. Examples of commonly used statins in the U.S. include Lipitor, Zocor, Parvachol, Lescol, Mevacor and Crestor. Rituximab (Rituxan), a monoclonal antibody, is often used alone or in conjunction with chemotherapy drugs to treat lymphomas. When administered to patients with lymphoma, rituximab attaches to CD20, a protein found on lymphoma cells. Addition of rituximab to chemotherapy improves outcomes in many lymphoma types. A laboratory-based study by Winiarska and colleagues published this year in The Public Library of Science Medicine journal suggested that statins may inhibit rituximab binding to CD20. "That finding raised questions about maintaining or stopping cholesterol treatment with statins for patients with lymphoma," says Grzegorz Nowakowski, M.D. (http://www.mayoclinic.org/bio/13657551.html), Mayo Clinic hematologist and lead researcher on the Mayo study. "One in five lymphoma patients take cholesterol-lowering statins; this corresponds to the potential for thousands of patients at risk of getting less or ineffective treatment due to statin interference with therapy," says Dr. Nowakowski. "In our prospectively followed cohort of patients, we found that statins did not interfere with rituximab and in some cases, may offer a benefit." The Mayo Clinic study included: 228 patients with diffuse large B-cell lymphoma, an aggressive form of the disease. Twenty-two percent of this group was taking statins when they started treatment for lymphoma. 293 patients with follicular lymphoma, an often indolent and slowly progressive form of the disease. Nineteen percent of patients were taking statins. Statins did not impinge treatment effectiveness for either group of patients. For patients with diffuse large B- cell lymphoma, statin use did not influence outcomes. Those with follicular lymphoma who took statins fared better than patients who didn't. At two years, 80 percent of those taking statins had no progression or re- treatment for their cancer versus 69 percent of those not taking statins. Dr. Nowakowski said these are early results and further validation in additional cohorts of patients is needed. This positive effect was seen regardless of the treatment approach for the lymphoma. Treatments included observation only, rituximab alone or rituximab in combination with chemotherapy medications. Dr. Nowakowski said that while oncologists at times recommend simplifying a patient's drug regimen before starting chemotherapy, many patients simply remain on statins during treatment. "We were concerned that these patients may be at risk of receiving less effective treatment due to statin interaction with rituximab. These results can provide reassurance to oncologists and their patients that statins will not reduce the effectiveness of rituximab and may in fact improve outcomes of some patients with lymphomas," he says. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- This research was a part of a large lymphoma epidemiology project at Mayo Clinic led by James Cerhan, M. D., Ph.D., and funded by University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE) The broader research program seeks to translate research findings into clinical practice. (http://cancercenter.mayo.edu/mayo/research/hematologic_malignancies/spore_lymphoma.cfm). Other Mayo Clinic researchers involved in the study led by Dr. Nowakowski are: Matthew Maurer; Thomas Habermann, M.D.; Stephen Ansell, M.D., Ph.D.; William Macon, M.D.; Kay Ristow; Cristine Allmer; Susan Slager, Ph.D.; Thomas Witzig, M.D.; and Dr. Cerhan. For more information on lymphoma treatment, please visit http://www.mayoclinic.org/lymphoma/. Source: Amy Tieder Mayo Clinic View drug information on Crestor; Lescol; Mevacor. 09 December 2008 - Roswell Park Researchers Clarify Mechanisms Of Novel Therapy In Non-Hodgkin's Lymphoma Cells A significant number of patients with non-Hodgkin's lymphoma have poor clinical outcomes because their cancer cells have become resistant to immunochemotherapy. Scientists at Roswell Park Cancer Institute hope to improve those outcomes by identifying the pathways that lymphoma cells develop to evade immunochemotherapy - and by developing novel therapeutic strategies to shut those pathways down. Obatoclax, a novel targeted cancer therapy , is capable of inducing two forms of cell death in B cell non- Hodgkin's lymphoma (B-NHL) cells and appears to have the potential to overcome acquired resistance to chemotherapeutic agents, according to a study conducted by Francisco J. Hernandez-Ilizaliturri, MD, Departments of Medicine and Immunology, RPCI. The research will be presented at the 2008 annual meeting of the American Society of Hematology, December 6-9, San Francisco, CA. B cell non-Hodgkin's lymphoma, a cancer of the cells of the lymph system, makes up about 85% of NHL cases diagnosed in the United States. The Bcl-2 family is a group of proteins known to affect patient outcomes and is involved in development, sustaining and progression of various subtypes of NHL. Dr. Hernandez-Ilizaliturri and colleagues examined the molecular mechanisms of Obatoclax, a targeted therapy, which is designed to inhibit several members of the Bcl-2 protein family. Studies were conducted in various rituximab-chemotherapy-sensitive or resistant B-cell lymphoma cell lines and in tumor cells isolated from 25 patients with different subtypes of B cell lymphomas and Hodgkin's disease. Dr Hernandez-Ilizaliturri and his group of investigators demonstrated that Obatoclax is a potent inhibitor of Bcl-2 family proteins, has significant anti-tumor activity against various rituximab-chemotherapy-sensitive or - resistant lymphoma cell lines, as well as in malignant B-cells derived from patients with diffuse large B cell lymphomas (DLBCL). In addition, they found that Obatoclax can enhance the biological activity of rituximab in vitro and sensitize NHL cells to the cytotoxic effects of a wide spectrum of chemotherapy agents. Scientist observed several signal events in NHL cells exposed to Obataclox, suggesting that this novel compound has a dual mechanism of action and is capable of inducing cell death (apoptosis) and/or cell self-degradation (autophagy) in B-NHL cell lines and can potentially be utilized to characterize shared pathways that regulate apoptosis, autophagy and possible necrosis within a given lymphomatous tumor. "As this class of agents moves forward in the treatment of hematological malignancies, the clinical optimization of Obatoclax and its incorporation into already available rituximab-chemotherapy regimens will likely be the result of translational research aimed at characterizing the molecular apoptotic and non- apoptotic (autophagy) pathways responsible for its anti-tumor activity" said Dr. Hernandez-Ilizaliturri. Roswell Park Cancer Institute, founded in 1898, is the nation's first cancer research, treatment and education center. The Institute was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. RPCI is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation's leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. Roswell Park Cancer Institute 09 December 2008 - Positive ELACYT(TM) Phase II Results - Data To Be Presented At ASH Clavis Pharma ASA (OSE: CLAVIS) announces positive interim clinical phase II results for ELACYT single agent therapy in patients with late stage acute myeloid leukaemia (AML). The results are presented today at the American Society of Haematology (ASH) 2008 conference. The patients included in the study represent a difficult to treat patient group that have failed two previous therapeutic regimens. This patient group constitutes a significant unmet medical need, as there are no efficacious treatments currently available for late stage AML. An analysis of the interim results from the ELACYT study shows that three of the first twenty patients have gone into complete remission. An independent data monitoring committee has reviewed the results and has recommended continuation of the study. Further enrolment of patients is ongoing. The interim results are presented today at the American Society of Haematology (ASH) 2008 conference at 5:30 PM - 7:30 PM (PST) in the Moscone Center, Hall A (Poster Board no.: I-54). "The results from the first 20 patients are most encouraging and represent a major step forward in our development of ELACYT, for the treatment of cancers of the blood" says Geir Christian Melen, CEO of Clavis Pharma. "The continued enrolment of patients has been rapid and clinical responses have been reported also in the next cohort of patients." ELACYT is currently in development in AML both as monotherapy for late stage patients and in combination with idarubicin for patients who have failed first course treatment. Clinical responses have been reported throughout the phase I and II parts of the program, and the safety profile looks favourable. ELACYT has previously been granted orphan drug designation by both the FDA and the European Commission for the treatment of AML. The ELACYT AML program involves 15 major cancer centres in the USA and Europe. About Leukaemia Approximately 300,000 new cases of leukaemia are diagnosed globally each year, resulting in around 220,000 deaths. Leukaemia represents a market with high unmet medical needs, which may open for accelerated approval processes to expedite market access for new drugs. It is a segmented market covering a broad variety of disorders. A major clinical concern is the high rate of disease recurrence. The five-year survival for the most common acute leukaemia type, acute myeloid leukaemia (AML), is in the range of 5- 10% for treated elderly patients, and approximately 30% for treated younger adults. About Clavis Pharma Clavis Pharma ASA is an oncology focused pharmaceutical company using its proprietary Lipid Vector Technology (LVT) platform to create New Chemical Entities (NCEs), by significantly improving already established drugs. The improvements are achieved by chemically binding specific unsaturated lipids to existing, and well understood, approved pharmaceuticals. Data generated suggests the resulting patentable NCEs offer improved efficacy and reduced side effects through enhanced pharmacokinetic properties, greater tissue penetration and, in many cases, additional modes of action. Clavis Pharma's objective is to develop its drug candidates until significant value has been created and proof of principle in man has been shown. For further clinical development and commercialisation of the products, Clavis Pharma will enter into strategic partnerships with established pharmaceutical or biotech companies. The company's product portfolio includes four new cancer drugs: ELACYT(TM) is in Clinical Phase II, Intravenous CP-4126 is in Clinical Phase I, Oral CP-4126 in Phase I, and CP-4200 is in early preclinical development. Results indicate that these products have promising potential for several cancer indications within solid tumours and leukaemia. The shares of Clavis Pharma ASA are listed on the Oslo Stock Exchange (ticker: CLAVIS). Additional information on Clavis Pharma can be found at: http://www.clavispharma.com/. Disclaimer The information contained herein shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of the securities referred to herein in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration, exemption from registration or qualification under the securities laws of any such jurisdiction. This news release contains forward-looking statements and forecasts based on uncertainty, since they relate to events and depend on circumstances that will occur in the future and which, by their nature, will have an impact on results of operations and the financial condition of Clavis Pharma. There are a number of factors that could cause actual results and developments to differ materially from those expressed or implied by these forward-looking statements. Theses factors include, among other things, risks associated with technological development, the risk that research & development will not yield new products that achieve commercial success, the impact of competition, the ability to close viable and profitable business deals, the risk of non-approval of patents not yet granted and difficulties of obtaining relevant governmental approvals for new products. No expressed or implied representations or warranties are given concerning Clavis Pharma or the accuracy or completeness of the information or projections provided herein, and no claims shall be made by the recipient hereof by virtue of this Information Memorandum or the information or projections contained herein. Any representations or warranties made to an investor in Clavis Pharma will be subject to separate sale and purchase agreements to be negotiated between the parties. Clavis Pharma(TM) and ELACYT (TM) are registered trademarks of Clavis Pharma ASA. Clavis Pharma ASA Positive ELACYT Phase II Results Clavis Pharma 09 December 2008 - International Clinical Study Confirms Effectiveness Of Lenalidomide For Patients With Relapsed, Aggressive Lymphoma Results of an international clinical study confirm the efficacy and safety of lenalidomide, an oral treatment, for patients with relapsed, refractory diffuse large B cell lymphoma (DLBCL). The research, led by Myron Czuczman, MD, Department of Medicine, Roswell Park Cancer Institute (RPCI), will be presented at the 2008 annual meeting of the American Society of Hematology, December 6-9, San Francisco, CA. Dr. Czuczman will discuss "Confirmation of the Efficacy and Safety of Lenalidomide Oral Monotherapy in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma: Results of An International Study," (Abstract # 268) at 7 am PT, Monday, December 8. Diffuse large B cell lymphoma is the most common subtype of non-Hodgkin lymphoma (NHL) in the United States, accounting for approximately one out of every three cases. Patients diagnosed with DLBCL who are not cured with standard CHOP chemotherapy plus rituximab or high-dose chemotherapy with autologous stem cell rescue have a poor prognosis and limited treatment options. This international phase II clinical study evaluated the efficacy of lenalidomide for 73 DLBCL patients with relapsed/refractory cancer who had received at least one prior treatment and had measurable disease. The median time from diagnosis to lenalidomide treatment was approximately two years and patients had received between one and six prior treatment regimens. The overall response rate to lenalidomide was 29% and included four percent who experienced a complete response; 25% partial response and 15% with stable disease. The most common toxicities of treatment were neutropenia (32%), thrombocytopenia (15%), asthenia (8%) and anemia (7%). "These results confirm an earlier, smaller U.S. based phase II study," said Dr. Czuczman. "Lenalidomide, administered orally and will manageable side effects, appears likely to become a potentially viable future treatment option for this group of non-Hodgkin's lymphoma patients who have failed previous therapies." Roswell Park Cancer Institute , founded in 1898, is the nation's first cancer research, treatment and education center. The Institute was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. RPCI is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation's leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit RPCI's website at http://www.roswellpark. org. Roswell Park Cancer Institute 09 December 2008 - Clinical Trial Finds Lenalidomide Safe As Single Therapy For Elderly CLL Patients The oral medication lenalidomide is safe and well-tolerated for elderly patients with chronic lymphocytic leukemia, a group without a well-defined frontline therapy for their disease, researchers from The University of Texas M. D. Anderson Cancer Center reported at the 50th annual meeting of the American Society of Hematology. "Lenalidomide has a favorable toxicity profile and shows signs of activity against CLL in our phase II clinical trial to date," said study presenter Alessandra Ferrajoli, M.D., associate professor in M. D. Anderson's Department of Leukemia. Patients start on a 5 mg dose of the drug in pill form and the dose escalates over time in 5 mg increments to a maximum of 25 mg. The median age of participants is 72. Chemo-immunotherapy therapy combinations that are effective in younger patients with CLL tend to be associated with a high rate of complications in patients older than 70, Ferrajoli said. Of 43 patients enrolled in the study, 35 were evaluable because they had been treated for at least three months. Nineteen of these (54 percent) achieved a partial response, where the disease is diminished, 14 patients (40 percent) had stable disease and continue on therapy, and two had their CLL progress. Lenalidomide also rapidly reduced the number of circulating lymphocytes - the hallmark of the disease - in the patients' blood. Ferrajoli said 47 percent achieved a blood complete response and 38 percent had at least a partial response. Patients on the trial for at least two months were evaluated for the drug's potential side effects. Of those 39 patients, 10 (26 percent) had decreased bone marrow activity resulting in a decrease in the number of either white blood cells called neutrophils or of platelets. Three patients had infections, two had fever and one had pneumonia. All patients registered in the study remain alive with 37 of the 43 continuing on treatment. Ferrajoli said the trial will include up to 60 patients. Lenalidomide, a drug developed by Celgene Corp. known commercially as Revlimid®, attacks both malignant cells and the cellular environment that nurtures them. The U.S. Food and Drug Administration has approved the drug for treatment of multiple myeloma and some forms of myelodysplastic syndrome. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- The clinical trial is funded by Celgene. Co-authors with Ferrajoli are Susan O'Brien, M.D., William Wierda, M.D., Ph.D., Stefan Faderl, M.D., Zeev Estrov, M.D., Kimberly Yerrow, R.N., Hagop Kantarjian, M.D., and Michael Keating, M.D., all of the Department of Leukemia; and Steven Kornblau, M.D. of the Department of Stem Cell Transplantation and Cellular Therapy and the Department of Leukemia. Ferrajoli has received honoraria and research funding from Celgene. O'Brien and Keating have consulted for Celgene. About M. D. Anderson The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For six of the past nine years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report. Source: Scott Merville University of Texas M. D. Anderson Cancer Center View drug information on Revlimid. 09 December 2008 - Potential Breakthrough For T-Cell Lymphoma Patients With Drug That Mimics Folic Acid Preliminary results of a pivotal Phase 2 clinical trial of pralatrexate (PDX), a drug that partially works by mimicking folic acid, showed a complete or partial response in 27 percent of patients with recurrent or resistant peripheral T-cell lymphoma (PTCL). PROPEL (Pralatrexate in patients with Relapsed Or refractory PEripheral T-cell Lymphoma) findings were presented by the study's principal investigator, Dr. Owen A. O'Connor of the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and NewYork-Presbyterian Hospital, at the 50th Annual Meeting of the American Society of Hematology (ASH) in San Francisco. The international, multicenter PROPEL trial is the largest ever conducted in patients with peripheral T-cell lymphoma -- a biologically diverse group of blood cancers that account for as many as 15 percent of non- Hodgkin's lymphoma (NHL) cases in the United States. There are currently no pharmaceutical agents approved for use in the treatment of either first-line or relapsed or refractory PTCL, and average five-year survival is approximately 25 percent. "These results indicate that pralatrexate produces a major durable response in patients for whom numerous prior treatments have been unsuccessful," says Dr. Owen A. O'Connor, director of the Lymphoid Development and Malignancy Program and chief of the Lymphoma Service at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital and Columbia University Medical Center, and associate professor of medicine at Columbia University College of Physicians and Surgeons. Prior to enrolling in the trial, eligible patients had received a median of three (range of 1 to 12) prior systemic treatment regimens, including 16 percent of patients who had previously undergone an autologous stem cell transplant. "Presently, there are no FDA-approved drugs for patients with PTCL, whether it is in the front-line or for patients with relapsed or refractory disease. This underscores the need for new therapies to treat this challenging disease. Pralatrexate has the potential to play a clinically meaningful role in the treatment of these patients," adds Dr. O'Connor. Pralatrexate, designed to look like the natural vitamin folic acid, disrupts DNA synthesis in tumor cells. The drug is designed to selectively accumulate in tumor cells, after which it then induces programmed cell death, or apoptosis, in the cancer cell. A total of 109 evaluable patients received 30 mg/m2 of pralatrexate intravenously once every week for six weeks followed by one week of rest per cycle of treatment. Patients also received vitamin B12 and folic acid supplementation. Response was assessed using standard International Workshop Criteria (IWC). In the trial, 69 percent of patients who responded did so after cycle one of therapy. The median duration of treatment in responding patients was 179 days at the time of this analysis. The duration of response exceeded three months in 17 of 29 responders (59 percent), including 6 of the 17 patients who continued on treatment. An accurate estimate of the median duration of response cannot be reported at this time due to the current length of follow up. Patients will continue to be followed until the median duration of response can be accurately estimated. The PROPEL trial is organized by Allos Therapeutics Inc., the maker of the drug. Since PROPEL has been given fast-track status, the company will submit pralatrexate for FDA approval once the Phase 2 data has been finalized -- sometime in the first half of 2009. Pralatrexate was developed by a team of researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) and the Southern Research Institute, including Dr. O'Connor, while at MSKCC. Dr. O'Connor and his colleagues identified the unique activity of pralatrexate in patients with lymphoma. Dr. O'Connor has continued to study pralatrexate at NewYork-Presbyterian/Columbia, now focusing on determining how the drug works in T-cell lymphoma, and on how best to combine it with other drugs to improve the treatment of patient with hematologic cancers. Peripheral T-Cell Lymphoma According to the American Cancer Society, approximately 66,000 patients are expected to be diagnosed with non-Hodgkin's lymphoma in the United States in 2008. Annual prevalence is estimated to be approximately 9,500 patients. In addition to the 30 to 50 percent of PTCL patients that do not respond to first-line treatment, a significant number of first-line multi-agent chemotherapy responders relapse or become refractory after treatment. Allos Therapeutics Inc. Allos Therapeutics is a biopharmaceutical company focused on developing and commercializing innovative, small-molecule drugs for the treatment of cancer. The Company's lead product candidate, pralatrexate (PDX), is a novel antifolate currently under evaluation in a pivotal Phase 2 (PROPEL) trial in patients with relapsed or refractory peripheral T-cell lymphoma. The PROPEL trial is being conducted under an agreement reached with the U.S. Food and Drug Administration under its special protocol assessment, or SPA process. The Company is also investigating pralatrexate in patients with non-small cell lung cancer, bladder cancer and a range of lymphoma sub-types. The Company's other product candidate is RH1, a targeted chemotherapeutic agent currently being evaluated in a Phase 1 trial in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). The Company currently retains exclusive worldwide rights to pralatrexate and RH1 for all indications. For additional information, please visit the Company's website at http://www.allos.com. Columbia University Medical Center Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The Medical Center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and state and one of the largest in the United States. NewYork-Presbyterian Hospital NewYork-Presbyterian Hospital -- based in New York City -- is the nation's largest not-for-profit, non- sectarian hospital, with 2,242 beds. It provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Allen Pavilion and NewYork-Presbyterian Hospital/Westchester Division. One of the largest and most comprehensive health care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. It ranks sixth in U.S.News & World Report's guide to "America's Best Hospitals," ranks first on New York magazine's "Best Hospitals" survey, has the greatest number of physicians listed in New York magazine's "Best Doctors" issue, and is included among Solucient's top 15 major teaching hospitals. The Hospital is ranked with among the lowest mortality rates for heart attack and heart failure in the country, according to a 2007 U.S. Department of Health and Human Services (HHS) report card. The Hospital has academic affiliations with two of the nation's leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons. NewYork-Presbyterian Hospital 09 December 2008 - Arzerra(TM) (ofatumumab) Demonstrates High Response Rates In Patients With Fludarabine Refractory Chronic Lymphocytic Leukemia (CLL) GlaxoSmithKline (GSK) and Genmab A/S (OMX: GEN) announced positive results from a pivotal trial pre- planned interim analysis of Arzerra(TM) (ofatumumab) in the treatment of refractory chronic lymphocytic leukemia (CLL). The results demonstrate the potential of ofatumumab for heavily pre-treated patients with CLL who do not respond to, or for whom currently available treatment options are not appropriate.(1) This research is being presented at the 50th Annual Meeting of the American Society of Hematology, 6-9 December, 2008. Ofatumumab is an investigational drug that has not been approved for any indication in any market at this time. The analysis included 138 patients with CLL who showed limited or no response (refractory) to both fludarabine and alemtuzumab treatment (double refractory; DR), and patients who were refractory to fludarabine and considered inappropriate candidates for alemtuzumab due to bulky tumor masses in their lymph nodes (bulky fludarabine refractory; BFR). The primary endpoint of the study was assessment of objective response.* The overall objective response rate seen in these patient groups treated with ofatumumab monotherapy was 58 percent for the DR group (n=59) and 47 percent for the BFR group (n=79); all responding patients had a partial remission (PR**) except for one patient with a complete remission (CR).(1) Median overall survival was 13.7 months for the DR group and 15.4 months for the BFR group;(1) response to ofatumumab treatment significantly correlated with longer patient survival. The median length of time that a patient lived without their disease getting worse (progression free survival) was 5.7 months for the DR group and 5.9 months for the BFR group.(1) The most common adverse events seen were infusion related reactions, which were mostly mild to moderate in severity. The most common serious adverse events (Grade 3 or 4) were infections (25 percent in DR; 25 percent in BFR), including one case of progressive multifocal leukoencephalopathy (PML) in a patient with progressive disease. Early death (within eight weeks from start of treatment) occurred in four patients (7 percent) in the DR group and two patients (3 percent) in the BFR group. Tumor lysis syndrome was also reported following treatment with ofatumumab. Common adverse reactions (greater than or equal to 10%) were pyrexia, cough, diarrhea, rash, neutropenia, fatigue, pneumonia, anemia, dyspnea, nausea, and upper respiratory tract infection. No patient tested positive for antibodies to ofatumumab.(1) "There is a great unmet medical need among patients with CLL that is refractory to conventional therapy. The clinical responses and the tolerability profile we are seeing with ofatumumab in this group of CLL patients are very encouraging," said lead investigator Professor Anders Osterborg, Department of Hematology, Karolinska Hospital, Stockholm, Sweden. In a post hoc, subset analysis prior treatment with rituximab did not have a significant effect on ofatumumab treatment efficacy. Of those patients who had received prior rituximab-containing therapy 54 percent in the DR group and 44 percent in the BFR group responded to treatment with ofatumumab.(1) "The positive results seen in this interim analysis reinforce the potential of ofatumumab in the treatment of CLL refractory to standard treatments," said Moncef Slaoui, Chairman Research and Development at GSK. "We are committed to the development of ofatumumab in both CLL and other disease settings to provide an additional treatment option to patients suffering from hematological malignancies." "Ofatumumab has helped responding patients who did not have other recognized treatment options," said Lisa N. Drakeman, Chief Executive Officer of Genmab. "We are working together with GSK to bring this urgently needed new medicine to market as quickly as possible, and are currently collaborating on filing submissions." Genmab and GSK now expect to file a Biologics License Application (BLA) filing with the US FDA in January 2009. CLL is the most common form of leukemia in the Western world,(2) and the treatment of patients with refractory disease remains a significant challenge. Patients who have not responded to current standard therapies, specifically patients whose disease is refractory to fludarabine and alemtuzumab treatment or patients who are refractory to fludarabine but whose diseases make them inappropriate for treatment with alemtuzumab, experience poorer outcomes. Only about 20 percent of patients respond to available salvage therapies.(3) Currently there is no approved drug for the treatment of this patient population. Ofatumumab is an investigational monoclonal antibody that targets a membrane-proximal (close to the cell surface), small loop epitope (a portion of a molecule to which an antibody binds) on the CD20 molecule on B cells.(4) This epitope is different from the binding sites targeted by other CD20 antibodies currently available or in development.(5) The CD20 molecule is a key target in CLL therapy because it is expressed in most B-cell malignancies.(6) About the study(1) The study includes patients with CLL refractory to both fludarabine and alemtuzumab, and patients who are refractory to fludarabine and considered inappropriate candidates for alemtuzumab due to bulky tumor masses in their lymph nodes. The study design calls for patients to receive eight weekly infusions of ofatumumab, followed by four monthly infusions. Patients receive 300 mg of ofatumumab at the first infusion and 2,000 mg of ofatumumab at each subsequent infusion. Disease status is assessed every four weeks until week 28 and then every three months until disease progression or month 24. The interim analysis included 138 treated patients (DR, n=59; BFR, n=79). Patient recruitment is ongoing and a final analysis will be conducted on the full study population, expected to be 100 patients in each group. The primary endpoint of the study is objective response over a 24 week period from start of treatment as assessed according to the National Cancer Institute Working Group guidelines by an Independent endpoint Review Committee (IRC). Secondary endpoints included duration of response, progression free survival, time to next CLL therapy, overall survival and adverse events. About ofatumumab Ofatumumab is being developed to treat chronic lymphocytic leukemia, follicular non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, rheumatoid arthritis and relapsing-remitting multiple sclerosis under a co- development and commercialization agreement between Genmab and GlaxoSmithKline. It is not yet approved for any indication in any country. About CLL CLL is the most common leukemia and one of the most common malignant lymphoid diseases.(2) Globally, leukemia accounts for some 300,000 new cases each year (2.8 percent of all new cancer cases) and 222,000 deaths.(7) GSK in Oncology GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK's revolutionary 'bench to bedside' approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes collaborations with more than 160 cancer centers. GSK is closing in on cancer from all sides with a new generation of patient-focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies. GlaxoSmithKline -- one of the world's leading research-based pharmaceutical and healthcare companies -- is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit http://www.gsk.com About Genmab A/S -- Genmab is a leading international biotechnology company focused on developing fully human antibody therapeutics for unmet medical needs. Using cutting-edge antibody technology, Genmab's world class discovery, development and manufacturing teams have created and developed an extensive pipeline of products for potential treatment of a variety of diseases including cancer and autoimmune disorders. As Genmab advances towards a commercial future, we remain committed to our primary goal of improving the lives of patients who are in urgent need of new treatment options. For more information on Genmab's products and technology, visit www.genmab.com. Refractory - term used to describe a disease that does not respond to treatment or returns within six months of completing such treatment Bulky tumors - when individual tumor masses are >5cm in diameter Salvage therapy - a final treatment for people who are non-responsive to or cannot tolerate other available therapies for a particular condition and whose prognosis is often poor Arzerra(TM) is the proposed registered trademark to be used in the United States and Europe. Cautionary statement regarding forward looking statements for GSK Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company's Annual Report on Form 20-F for 2007. Forward looking statement for Genmab This press release contains forward looking statements. The words "believe", "expect", "anticipate", "intend" and "plan" and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with product discovery and development, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products obsolete, and other factors. For a further discussion of these risks, please refer to the section "Risk Management" in Genmab's Annual Report, which is available on www.genmab.com. Genmab does not undertake any obligation to update or revise forward looking statements in this press release nor to confirm such statements in relation to actual results, unless required by law. References (1) Osterborg A, Kipps et al. Ofatumumab (HuMax-CD20), a Novel CD20 Monoclonal Antibody, Is An Active Treatment for Patients with CLL Refractory to Both Fludarabine and Alemtuzumab or Bulky Fludarabine-Refractory Disease: Results from the Planned Interim Analysis of An International Pivotal Trial. Abstract #328. Presented at the American Society of Hematology Annual Meeting 2008 (2) Shanafelt TD, Byrd JC, et al. Narrative review: initial management of newly diagnosed, early-stage chronic lymphocytic leukemia. Ann Intern Med. 2006 Sep 19;145(6):435-47. (3) Tam CS, O'Brien S, et al. The natural history of fludarabine-refractory chronic lymphocytic leukemia patients who fail alemtuzumab or have bulky lymphadenopathy. Leukemia and Lymphoma 2007;48(10): 1931-1939 (4) Hagenbeek A, Gadeberg O, et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood, 2008; 111: 5486-5495 (5) Teeling JL, Mackus, W,J., et al. The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20. J Immunol 2006; 177: 362-371 (6) Glennie MJ, French RR, et al. Mechanisms of killing by anti-CD20 monoclonal antibodies. Molecular Immunology, 2007;44 (16):3823-3837 (7) Parkin DM, Bray F, et al. Global Cancer Statistics, 2002. CA Cancer J Clin 2005; 55:74-108 GlaxoSmithKline http://www.gsk.com 09 December 2008 - Medarex Announces Enhanced Activity Data With Second Generation Anti-CD30 Antibody For Malignant Lymphoma Medarex, Inc. (Nasdaq: MEDX) announced results from a preclinical study for MDX-1401, a second- generation non-fucosylated version of MDX-060 that targets CD30, a marker for activated lymphocytes that is present on the malignant cells of Hodgkin's lymphoma (HL) as well as other CD30-expressing cancers. MDX-1401 demonstrated almost a doubling in potency and efficacy in cell lines when compared to MDX-060. The improved potency and efficacy of MDX-1401 in in vivo xenograft models indicates enhanced antibody-dependent cellular cytotoxicity (ADCC) activity, an important mechanism of action of therapeutic antibodies. In addition to anti-tumor activity, the preclinical data showed a statistically significant increase in median survival time for the MDX-1401 treatment group when compared to the MDX-060 treatment group. The data were presented in a poster presentation entitled "Characterization of MDX-1401, a human anti- CD30 antibody with enhanced effector function, for therapy of malignant lymphoma" (abstract #1580) at the 50th Annual Meeting of the American Society of Hematology (ASH) being held December 6-9, 2008 in San Francisco, CA. "We are excited with the growing body of scientific evidence that indicates enhanced ADCC and improved anti-tumor efficacy with the second generation anti-CD30 antibody, MDX-1401, as compared to MDX- 060," said Geoffrey M. Nichol, MBChB, Senior Vice President of Product Development at Medarex. "The data we have seen to date continues to inform our development plans and underscores the importance of assessing MDX-1401 as a potentially more potent therapeutic for CD-30 expressing malignancies. We look forward to presenting results from the ongoing Phase 1 MDX-1401 study and the recently completed Phase 2 MDX-060 study in 2009." More information about the ASH Annual Meeting may be found at www.hematology.org About MDX-1401 MDX-1401 is a non-fucosylated version of the MDX-060 antibody and is enhanced for greater antibody- dependent cellular cytotoxicity (ADCC) activity, an important function of the human immune system, whereby immune cells can kill target cells. ADCC activity is one important mechanism underlying the efficacy of some currently approved anti-cancer antibodies. A dose-escalation, multi-dose Phase 1 clinical trial of MDX-1401 in up to 36 patients with relapsed or refractory Hodgkin's lymphoma (HL) is currently ongoing, with results expected in 2009. The trial is designed to establish and evaluate the safety profile and initial efficacy of the antibody. About Medarex Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb(R) technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. Over forty of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with the most advanced product candidates currently in Phase 3 clinical trials or the subject of regulatory applications for marketing authorization. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world's unmet healthcare needs. For more information about Medarex, visit its website at http://www.medarex.com. Medarex Statement on Cautionary Factors Except for the historical information presented herein, the statements relating to MDX-1401 in this press release may constitute forward-looking statements, as defined in the Private Securities Litigation Reform Act of 1995, that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Medarex disclaims, however, any intent or obligation to update these forward-looking statements. Risks and uncertainties include risks associated with product discovery and development of MDX-1401, as well as risks detailed from time to time in Medarex's public disclosure filings with the U.S. Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the fiscal year ended December 31, 2007 and its quarterly reports on Form 10-Q. Copies of Medarex's public disclosure filings are available from its investor relations department. Medarex(R), the Medarex logo and UltiMAb(R) are registered trademarks of Medarex, Inc. All rights are reserved. 09 December 2008 - SuperGen's PIM Kinase Inhibitor, SGI-1776, Effective In Pre-Clinical Models Of Acute Lymphoblastic Leukemia SuperGen Inc. (Nasdaq: SUPG), a pharmaceutical company dedicated to the discovery and development of novel cancer therapies, announced that its oral PIM kinase inhibitor, SGI-1776, is effective both in vitro and in vivo in preclinical models of acute lymphoblastic leukemia (ALL) (Abstract #1922). This research was presented at the 50th Annual Meeting of the American Society of Hematology. In a poster presentation entitled "Inhibiting PIM-1 is effective in vitro and in vivo against ALL: A novel mechanistic and potentially clinically relevant druggable target," Dr. Valerie Brown and colleagues from Children's Hospital of Philadelphia and University of Pennsylvania demonstrated that SGI-1776 inhibited human ALL cell lines in a dose-dependent manner. Furthermore, SGI-1776 and the m-tor inhibitor rapamycin acted synergistically to inhibit ALL cell proliferation. In a clinically relevant in vivo model, NOD/SCID mice xenografted with human primary ALL cells, SGI-1776 also reduced tumor burden. "Our PIM kinase inhibitor, SGI-1776, has significant potential in hematologic malignancies," commented Dr. Gregory Berk, Chief Medical Officer of SuperGen. "PIM-1 is known to be overexpressed in ALL, AML, CML, as well as non-Hodgkin's lymphoma. In many of these conditions PIM-1 overexpression is a poor prognostic factor. It has been postulated that inhibition of PIM kinase may potentiate the activity of m-tor inhibitors by modulation of m-tor inhibitor resistance pathways. These elegant preclinical experiments by Dr. Brown and her colleagues at the University of Pennsylvania support this hypothesis." SuperGen recently received clearance for a phase I trial with SGI-1776 in patients with non-Hodgkin's lymphoma and prostate cancer, and plans to initiate a second phase I trial of SGI-1776 in patients with relapsed/refractory leukemias in 2009. Copies of the poster presentations at the ASH Annual Meeting are available in the pipeline section of SuperGen's Web site http://www.supergen.com. About SGI-1776 SGI-1776 inhibits the three human PIM kinases (PIM-1, PIM-2 and PIM-3). PIM kinases are highly conserved serine-threonine kinases that are key regulators in many signaling pathways implicated in cancer. When expressed, PIM kinases are strong survival factors and can induce progression of the cell cycle, inhibition of apoptosis, and modulation of other signal transduction pathways. Therefore, SGI-1776 can induce cell death in cancer cells expressing PIM kinases and promote sensitivity of cancer cells to treatment with other targeted and chemotherapy drugs. SGI-1776 has broad potential as a single agent as well as in combination with other agents, as PIM kinases contribute to many malignancies including prostate adenocarcinomas, diffuse large cell lymphomas, as well as several types of leukemias. About SuperGen Based in Dublin, Calif., SuperGen, Inc. is a pharmaceutical company dedicated to the discovery and development of novel cancer therapies. SuperGen is developing a number of therapeutic anticancer products focused on kinase and cell signaling inhibitors and DNA methyltransferase inhibitors. Forward Looking Statements This news release contains certain "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as "believes," "expects," "anticipates," "intends," "will," "may," "should," or similar expressions. These forward-looking statements are not guarantees of future performance and involve a number of risks and uncertainties that may cause actual results to differ materially from the results discussed in these statements. Factors that might cause the company's results to differ materially from those expressed or implied by such forward-looking statements include, but are not limited to, the ability to discover, develop and move target compounds into clinical development and other risks and uncertainties detailed from time to time in the company's filings with the Securities and Exchange Commission including its most recently filed Form 10-Q and 10-K. SuperGen, Inc. undertakes no duty to update any of these forward-looking statements to conform them to actual results. SuperGen, Inc. http://www.supergen.com 09 December 2008 - Zevalin Consolidation In Patients With Complete Remission After Induction Therapy Results In Durable Remission Of More Than 67 Months Cell Therapeutics, Inc. (CTI) (Nasdaq and MTA: CTIC) announced that extended follow-up data for the Zevalin(R) ([90Y]-ibritumomab tiuxetan) First-line Indolent (FIT) study presented at the American Society of Hematology (ASH) 50th Annual Meeting by Morschhauser, et al demonstrated the continued improvement in progression-free survival (PFS) following Zevalin consolidation therapy for patients with follicular B-cell non-Hodgkin's lymphoma who achieved a response to first line therapy over chemotherapy alone. Additionally, Zevalin consolidation did not adversely affect the use of various effective second-line treatments including stem cell transplants in patients who relapsed. "The FIT study follow-on results are quite impressive when one considers that the median progression free survival for the Zevalin recipients that achieved a complete remission (CR) after induction therapy has not yet been reached with an estimated 67 months compared to 30 months with chemotherapy alone," said James A. Bianco, M.D., CEO of Cell Therapeutics. "A single dose of consolidation that could allow patients with a CR from requiring additional treatment for their NHL for over 3 years represents a significant advancement in the treatment of this disease." The multinational, randomized phase III FIT study evaluated the benefit and safety of a single infusion of Zevalin in patients with follicular B-cell non-Hodgkin's lymphoma who had achieved a partial remission (PR) or a complete remission / complete remission unconfirmed (CR/CRu) after receiving standard first-line chemotherapy regimens. Patients were randomized to either Zevalin consolidation or no further therapy. The FIT trial results were first presented at the December 2007 ASH annual meeting. The results were subsequently published in Journal of Clinical Oncology 2008 26(32):5156-64. At the 2008 ASH meeting, the investigators presented an additional 1-year follow-up (median follow-up of 42 months) of the FIT study that included 409 patients who achieved a CR/CRu or PR after induction therapy. Patients that achieved a CR after induction therapy achieved a median PFS of >67 months for the Zevalin arm compared to 30.8 in the control arm (HR 0.61[95% CI .41-.91]; p = 0.015). Patients that achieved a PR after induction therapy achieved a median PFS of 29.6 months for the Zevalin arm compared to 6.7 months in the control arm (HR 0.36[95% CI .25-.51]; p < 0.001). Subsequent therapy with various modalities including chemotherapy, radiotherapy, immunotherapy, Zevalin and stem cell transplation (ASCT) was given to 63 patients in the Zevalin arm and 108 patients in the control arm, who achieved an overall response rate of 81% and 73%, respectively. The results demonstrate that administration of Zevalin as consolidation therapy does not preclude the use of effective second line therapies. No previously unreported toxicities were noted and there was no increase in the incidence of secondary malignancies to date in patients treated with Zevalin as compared to control patients. CTI has submitted a supplemental Biologics License Application (sBLA) to the FDA based on the FIT data obtained through an agreement with Bayer Schering Pharma AG, Germany. The FDA has accepted the application for review and granted a priority review status with a Prescription Drug User Fee Act (PDUFA) target date of April 2, 2009 for a decision on the application. About First-Line Consolidation Therapy Consolidation therapy is a treatment given after initial induction therapy and is aimed at improving the quality of the patient response by further diminishing the number of cancer cells with the goal of extending the response duration. About Zevalin(R) Zevalin(R) (Ibritumomab Tiuxetan) is a form of cancer therapy called radioimmunotherapy and is indicated as part of the Zevalin therapeutic regimen for treatment of relapsed or refractory, low-grade or follicular B- cell non- Hodgkin's lymphoma, including patients with rituximab refractory follicular NHL. Zevalin is also indicated, under accelerated approval, for the treatment of relapsed or refractory, rituximab-naive, low- grade and follicular NHL based on studies using a surrogate endpoint of overall response rate. It was approved by the FDA in February of 2002 as the first radioimmunotherapeutic agent for the treatment of NHL. Rare deaths associated with an infusion reaction symptom complex have occurred within 24 hours of rituximab (Rituxan(R)) infusions. Yttrium-90 Zevalin administration results in severe and prolonged cytopenias in most patients. Severe cutaneous and mucocutaneous reactions have been reported. The most serious adverse reactions of the Zevalin therapeutic regimen were primarily hematologic, including neutropenia, thrombocytopenia and anemia. Infusion-related toxicities were associated with pre- administration of rituximab. The risk of hematologic toxicity correlated with the degree of bone marrow involvement prior to Zevalin therapy. Myelodysplasia or acute myelogenous leukemia was observed in 2 percent of patients (8 to 34 months after treatment). Zevalin should only be used by health care professionals qualified by training and experience in the safe use of radionuclides. Patients and healthcare professionals can visit http://www.zevalin.com for more information. About Non-Hodgkin's Lymphoma Non-Hodgkin's lymphoma (NHL) is caused by the abnormal proliferation of white blood cells and normally spreads through the lymphatic system, a system of vessels that drains fluid from the body. NHL can be broadly classified into two main forms -- aggressive NHL, a rapidly spreading acute form of the disease, and indolent NHL, which progresses more slowly. According to the National Cancer Institute's SEER database there were nearly 400,000 people in the U.S. with NHL in 2004. The American Cancer Society estimates that in the United States 66,120 people are expected to be diagnosed with NHL in 2008. Additionally, approximately 19,160 are expected to die from this disease in 2008. About Cell Therapeutics, Inc. Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of Zevalin include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with Zevalin in particular including, without limitation, the potential for Zevalin FIT data to be acceptable to the FDA for this expanded indication or any other indication, the determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, and costs of developing, producing and selling Zevalin, and the ability of CTI to continue to raise capital to fund its operations. There is also a risk that even if label expansion of Zevalin is approved, it may not result in a significant market increase for the drug due to the presence of other treatment options, failure to gain market acceptance and other factors. You should also review the risk factors listed or described from time to time in the Company's filings with the Securities and Exchange Commission including, without limitation, the Company's most recent filings on Forms 10-K, 8-K, and 10-Q. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise. Cell Therapeutics, Inc. http://www.celltherapeutics.com --- 08 December 2008 - Seattle Genetics Reports Durable Objective Responses With SGN-35 In Lymphoma - American Society Of Hematology 50th Annual Meeting Seattle Genetics, Inc. (Nasdaq: SGEN) today reported data from a phase I clinical trial of SGN-35, an antibody-drug conjugate (ADC), demonstrating multiple complete and partial responses at well-tolerated doses in patients with relapsed or refractory Hodgkin lymphoma and other CD30-positive hematologic malignancies. The data were presented during the American Society of Hematology (ASH) 50th Annual Meeting in San Francisco, California. Based on data from the phase I study, the company is finalizing its U. S. registration pathway and plans to initiate pivotal trials of SGN-35 in the first half of 2009. Out of 44 evaluable patients treated with SGN-35, 17 patients achieved objective responses, including nine complete responses and eight partial responses. Eighteen additional patients had stable disease and nine patients progressed. The median duration of response was 22 weeks, with 11 responses still ongoing. Across all dose levels, 86 percent of the 42 patients who had at least one post-baseline assessment achieved reductions in tumor volume. Among 28 evaluable patients treated at doses of 1.2 milligrams per kilogram (mg/kg) and higher, 54 percent achieved an objective response, including 32 percent with complete responses. Furthermore, 93 percent of these patients achieved tumor reductions, and their median progression-free survival was greater than six months. "Patients with Hodgkin lymphoma who relapse following stem cell transplant have limited therapeutic options, and those who relapse within six months have a short predicted survival," said Anas Younes, M.D., Professor of Medicine and Director, Clinical and Translational Research in the Department of Lymphoma/Myeloma at MD Anderson Cancer Center, and presenting investigator of the phase I study. "These phase I data are encouraging, and provide evidence that SGN-35 may offer an important new therapeutic option for patients in this setting." SGN-35 is an ADC comprising an anti-CD30 antibody attached by an enzyme-cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE), using Seattle Genetics' proprietary technology. The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalization into CD30- expressing tumor cells, resulting in a targeted cell-killing effect. "These promising data, including tolerability profile, response rate and durability of responses, suggest that SGN-35 has meaningful therapeutic potential, and we believe it warrants our aggressive development plans," said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "We are positioning the program for pivotal trials to begin in the first half of 2009." SGN-35 Phase I Study Data from 45 patients treated on the single-arm, dose-escalation study of SGN-35 were presented, including 42 with Hodgkin lymphoma, two with systemic anaplastic large cell lymphoma (ALCL) and one with angioimmunoblastic T-cell lymphoma. Cohorts of patients received doses of SGN-35 every three weeks, escalating from 0.1 mg/kg to 3.6 mg/kg. The median age of patients was 36 years. Enrolled patients had received a median of three prior chemotherapy regimens and 73 percent had received a prior autologous stem cell transplant. SGN-35 was generally well tolerated. The majority of adverse events were Grade 1 and 2, with the most common being fatigue, fever, diarrhea and nausea. The maximum tolerated dose was defined as 1.8 mg/kg administered every three weeks. A downloadable copy of Seattle Genetics' SGN-35 poster is available from the "Technology" section of the company's website at www.seattlegenetics.com. About CD30-Positive Lymphoma Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. A defining attribute of the Reed-Sternberg cell is its expression of the CD30 antigen. According to the American Cancer Society, approximately 8,200 cases of Hodgkin lymphoma will be diagnosed in the United States during 2008. An additional 2,000 to 3,000 patients per year in the United States are diagnosed with ALCL, a T-cell non-Hodgkin lymphoma that expresses the CD30 antigen. About Seattle Genetics Seattle Genetics is a clinical stage biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer and autoimmune disease. The company has four product candidates in ongoing clinical trials: dacetuzumab (SGN-40), lintuzumab (SGN-33), SGN-35 and SGN-70. Dacetuzumab is being developed under a worldwide collaboration with Genentech. In addition, the company has developed proprietary antibody-drug conjugate (ADC) technology comprising highly potent synthetic drugs and stable linkers for attaching the drugs to monoclonal antibodies. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Genentech, Bayer, CuraGen, Progenics, Daiichi Sankyo and MedImmune, a subsidiary of AstraZeneca, as well as an ADC co-development agreement with Agensys, a subsidiary of Astellas Pharma. Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential therapeutic benefit of SGN-35 and plans for future clinical trials. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include risks related to adverse clinical results as SGN-35 advances in clinical trials, such as patients exhibiting progressive disease or severe adverse events. In addition, our regulatory plans may change as a result of consultation with the FDA or additional information from our clinical trials. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company's filings with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. 08 December 2008 - Adding Rituximab (MabThera) To Chemotherapy Almost Doubles Complete Remission For People With Chronic Lymphocytic Leukaemia (CLL) Impressive new data presented today from two landmark studies show that a new 'immunochemotherapy' treatment combination allows people with the most common form of leukaemia(1,2,3) to almost double their chance of achieving a complete remission*, compared to those treated with chemotherapy alone(4,5). One study of 817 previously untreated CLL patients (CLL-8 trial) showed that adding the targeted cancer treatment rituximab (MabThera) to chemotherapy (a combination known as R-FC) meant they were almost twice as likely to achieve complete remission compared to those treated with chemotherapy (FC) alone (52% vs. 27%)(4). In a separate study (REACH), the same immunochemotherapy combination was shown to stop the disease in its tracks in relapsed patients for an additional 10 months when compared to FC chemotherapy alone(5). In this study, complete remission rates were also nearly doubled in the R-FC arm: 24 per cent versus 13 per cent of those given FC alone(5). Results from both studies are being announced today at the American Society of Haematology (ASH) Annual Meeting in San Francisco. Professor Andrew Pettitt, Consultant Haematologist at Royal Liverpool University Hospital and a UK investigator in the REACH study said: "These results represent a significant advance, and will change the way we approach the treatment of CLL. The goals of treatment are to shrink the disease to the point where we cannot detect it, and to maximise the length of time before the cancer returns. "The new rituximab-led immunochemotherapy will give many patients the opportunity of living longer without their disease progressing, and many of these will have no signs or symptoms for an extended period of time," Professor Pettitt said. This research suggests that, in many cases, immunochemotherapy is likely to become the new standard first- (4) and second-line(5) treatment for fit CLL patients. CLL is the most common form of leukaemia(1,2,3) and there are an estimated 3,400 new cases each year (6). The disease is twice as common in men as in women, with incidence rapidly increasing after the age of 50 years(6). Professor Andrew Pettitt commented further: "The addition of rituximab to FC chemotherapy delivers deeper, longer-lasting remission for CLL patients who have experienced relapse. When treated with the new combination, patients potentially will remain progression free by almost a year longer than if they had been given FC alone." First-line treatment with rituximab plus FC chemotherapy almost doubles remission numbers and prolongs progression-free survival compared to chemotherapy alone The landmark CLL-8 trial showed that 52 per cent of patients in the R-FC arm achieved a complete response (complete remission) versus 27 per cent of patients in the FC arm4. Progression-free survival was significantly improved in the R-FC arm: 76.6 per cent of patients showed no signs that their disease had progressed two years into the trial, compared to 62.3 per cent given FC only(4). Relapsed patients The REACH trial compared R-FC with FC, in people with CLL who had had one course of chemotherapy previously and who required further treatment. Those in the R-FC arm extended their progression-free survival by 10 months compared with those given FC (30.6 months versus 20.6 months respectively)(5). This constituted a 50 per cent improvement for R-FC compared to FC. Complete remission rates were also nearly doubled in the R-FC arm: 24 per cent versus 13 per cent of those given FC alone(5). Tolerability In the REACH trial, the adverse events seen were very similar between both arms, with low white cell count and infections being the main events seen5. In the CLL-8 trial, adding rituximab to FC led to a significantly higher incidence of a low white cell count (which raises susceptibility to infection), but this susceptibility did not lead to a marked difference in infections between the two types of treatment(4). Rituximab is not currently licensed for the treatment of CLL A European marketing licence application was filed for rituximab for previously untreated patients with CLL in July 2008. If the licence application is successful, rituximab should be available for this group of UK CLL patients in the first half of 2009. Notes * Complete remission means that all signs of the disease are clinically undetectable, although a few cancer cells may remain in the body. About chronic lymphocytic leukaemia (CLL)(2) Chronic Lymphocytic Leukaemia (CLL) is a slowly progressive form of cancer, characterised by an increased number of B lymphocytes, a type of white blood cell that is involved in fighting infection. Blood cells are normally produced in a controlled way, but in CLL the process gets out of control. The lymphocytes multiply too quickly and live too long, so there are too many of them circulating in the blood. These leukaemia lymphocytes look normal, but are in fact not properly developed and do not work properly. Over a period of time the abnormal cells replace the normal white cells, red cells and platelets in the bone marrow. It is the most prevalent form of leukaemia and occurs predominantly in patients over 55 years. About MabThera (rituximab)(7) Non-Hodgkin lymphoma (NHL) Rituximab is currently approved for first-line use for patients with advanced follicular NHL in combination with the chemotherapy, in patients with follicular lymphoma who are resistant to chemotherapy or in second or subsequent relapse. It is also approved for use as maintenance treatment in patients with relapsed or refractory follicular lymphoma who have responded to re-induction therapy and in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy for patients with diffuse large B-cell NHL. Rituximab works to tackle CLL through three distinct modes of action: 1. Complement-dependent cytotoxicty (CDC): Where rituximab binds to CD20, activating a large protein complex. This results in the formation of holes in the B-cell membrane, flooding the cell, which leads to death 2. Antibody-dependent cell mediated cytotoxicty (ADCC): Where rituximab binds to CD20 and recruits cells that defend the body in an immune response. These cells in turn engulf the bound B- cell and destroy it 3. Apoptosis: Where the binding of rituximab to the B-cells signals the malignant cells to self-destruct About CLL-8 CLL-8 was a multi-centre, multinational, randomised phase III trial of 817 patients with CLL who needed treatment for the first time. The trial was designed to evaluate the efficacy and tolerability of R- FC versus FC for initial treatment. About REACH REACH was an open-label, multi-centre, multinational randomised phase III study of 552 patients with relapsed/ refractory CLL. The trial was designed to evaluate the efficacy and tolerability of R-FC versus FC. The primary end-point was progression free survival. About Roche in the UK Roche aims to improve people's health and quality of life with innovative products and services for the early detection, prevention, diagnosis and treatment of disease. Part of one of t he world's leading healthcare groups, Roche in the UK employs nearly 2,000 people in pharmaceuticals and diagnostics. Globally Roche is the leader in diagnostics, and a major supplier of medicines for the treatment of cancer, transplantation, virology, bone and rheumatology, obesity and renal anaemia. Find out more at http://www. rocheuk.com. References 1. http://www.cancerbackup.org.uk/Cancertype/Leukaemiachroniclymphocytic/General/WhatisCLL; accessed 2 December 2008 2. http://www.cllsupport.org.uk/aboutcll.htm; accessed 2 December 2008 3. http://www.cancerhelp.org.uk/help/default.asp?page=17964; accessed 2 December 2008 4. 'Chemoimmunotherapy with Fludarabine (F), Cyclophosphamide (C) and Rituximab (R) (FCR) versus Fludarabine and Cyclophosphamide (FC) improves response rates and progression-free survival (PFS) in previously untreated patients (pts) with advanced lymphocytic leukaemia (CLL)', Hallek M. et al, abstract presented at the 50th ASH Annual Meeting and Exposition, December 6-9, 2008, San Francisco CA 5. 'Rituximab, Fludarabine and Cyclophosphamide (R-FC) prolongs progression free survival in relapsed or refactory chronic lymphocytic leukaemia (CLL) compared with FC alone: Final results from the International Randomized Phase III REACH Trial', Tadeusz Robak et al, abstract presented at the 50th ASH Annual Meeting and Exposition, December 6-9, 2008, San Francisco CA 6. Chronic lymphocytic leukaemia, G Dighiero, T J Hamblin, Lancet 2008; 371: 1017-2975 http://www. cllsupport.org.uk/aboutcll.htm 7. Rituximab summary of product characteristics Source: Louise Pontifex Roche 08 December 2008 - First International Conference On Inflammatory Breast Cancer The University of Texas M. D. Anderson Cancer Center held the first international inflammatory breast cancer (IBC) conference on December 6-7, to bring together internationally recognized breast cancer clinicians and scientists. Participants presented new clinical discoveries and participated in educational workshops, with the goal of improving diagnosis and management of this rare but deadly disease. During the conference, the new IBC International Consortium was formalized to develop joint international projects aimed at raising global awareness, increasing education and seeking funding to study the disease. The Consortium consisted of participants from ten countries, including: Australia, Belgium, Egypt, France, Italy, Japan, Spain, Tunisia, the United Arab Emirates and the United Kingdom. Among its first projects, the Consortium plans to establish a database of IBC cases that will include a tissue and serum bank. "We are assembling researchers from around the world who are passionate about advancing progress against this disease," says Massimo Cristofanilli, M.D., associate professor in M. D. Anderson's Department of Breast Medical Oncology and Director of the Morgan Welch Inflammatory Breast Cancer Research Program and Clinic. "This is the first conference dedicated exclusively to exchanging knowledge and discussing the complexities of IBC. Our goal is to step up the pace of research and education - ultimately saving women's lives." IBC is a rare, fast-growing and aggressive cancer. It can spread in just a few weeks, and is often mistaken for something other than breast cancer, such as a rash or infection. Survival for women with IBC can be impeded by delays in diagnosis, a lack of expertise in treating IBC and its resistance to treatment with standard chemotherapy. IBC represents up to two percent of all breast cancer cases diagnosed each year in the United States; its prevalence globally is unclear due to its common misdiagnosis. Research presented at the conference included an analysis of under-reporting of IBC; a potential new molecular target for prevention and treatment of metastases in IBC; and a new target for IBC treatment showing promise in preclinical phase. For example, one study presents a method that targets the epidermal growth factor receptor, a pathway that plays an important role in tumor growth, mortality and invasion of IBC and which is over expressed in 30 percent of IBC cases; another examines the use of vorinostat, a drug commonly used to treat cutaneous T-cell lymphoma, to treat the aggressive cases of IBC that recur on the skin with invasion into the dermal lymphatics. M. D. Anderson has seen nearly 200 new cases of IBC in the last two years - more than any other institution in the country. In 2006, the institution unveiled the Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, the largest clinic in the world devoted to inflammatory breast cancer research and care. The clinic is composed of a dedicated group of 16 clinical and pre-clinical investigators spanning six divisions, including cancer medicine, diagnostic imaging, pathology/laboratory medicine, prevention, radiation oncology and surgery. Investigators have identified high-impact goals for clinical and pre-clinical studies, all focused on improved patient care through management and discovery. "We are making great strides for women suffering from IBC," Cristofanilli says. "We are dedicated to disseminating research and information about the disease that will benefit women all over the world in terms of both diagnosis and treatment." ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- About M. D. Anderson The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For four of the past six years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report. Source: Laura Sussman University of Texas M. D. Anderson Cancer Center 08 December 2008 - Hairy-Cell Leukemia: 50 Years Of Research In 1958, Ohio State University cancer researcher Dr. Bertha Bouroncle first identified a deadly disease now known as hairy-cell leukemia, a once fatal disease that can now be effectively treated. Now, 50 years later researchers from across the globe are gathering for a symposium titled "50 years of Enormous Progress in Hairy Cell Leukemia: A Celebration of Clinical Research with Remaining Unanswered Questions." Hairy-cell leukemia is a relatively rare form of adult chronic leukemia that affects white blood cells called B lymphocytes. This disease was once uniformly fatal, but highly successful therapies have been developed, and patients today who receive proper treatment can have a relatively normal quality of life. Dr. Michael Grever, chairman of the department of internal medicine at Ohio State and co-leader of the Experimental Therapeutics program at The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, is one of seven leukemia experts who will lead the meeting. The investigators also plan to establish an international association devoted to hairy-cell leukemia research. "This seminar celebrates the progress we've made in hairy-cell leukemia, yet recognizes the work that still needs to be done," said Grever, who specializes in hematologic malignancies. "We want to show practicing oncologists that in the past 50 years, we've gone from a fatal, untreatable disease to one that can be treated effectively, allowing patients to live relatively normal lives." Other presenters include Dr. John Cawley, department of haematology at the University of Liverpool in the U.K.; Dr. Robert J. Kreitman, clinical immunotherapy section, National Institutes of Health in Bethesda, Maryland; Francesco Lauria, division of hematology and transplantation medicine immunological services, University of Siena in Siena, Italy; Dr. Alan Saven, division of hematology and oncology, Scripps Clinic, and Ida M. and Cecil Green Cancer Center, La Jolla, Calif.; Dr. Deborah Thomas, department of leukemia, University of Texas M.D. Anderson Cancer Center in Houston; and Dr. Pier Luigi Zinzani, University of Bologna in Bologna, Italy. Hairy-cell leukemia is rare, accounting for only about 500 new cases each year, or about 2 percent of all leukemias. As a result, hematologists may encounter this disease only a few times in their career. Symposium attendees will learn to: Identify the clinical presentation and complications associated with hairy-cell leukemia. Recognize the correct diagnosis and distinguish this disease from numerous lymphoid malignancies. Indicate the correct time to initiate systemic therapy and select the appropriate regimen. Outline the management of care when patients relapse or fail to respond to therapy, and utilize supportive care to prevent and manage infection in the patient with hairy-cell leukemia. "We still need to do more research," says Grever. "This is like taking the football down to the 5-yard line and not getting the touchdown." Grever will discuss long-term follow-up studies of patients who were treated for hairy-cell leukemia, including studies he conducted with Bouroncle and Dr. Eric Kraut at Ohio State's Medical Center. Bouroncle spent her entire career at Ohio State, and is now a faculty emeritus in the department of internal medicine. Hairy-cell leukemia is seven times more common among elderly men than elderly women. Patients with this disease often have low platelet counts and blood counts, anemia and are at high risk for developing infections, Grever said. Symptoms may include fatigue, infections and weight loss. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute is one of only 40 NCI-designated Comprehensive Cancer Centers in the United States and the only freestanding cancer hospital in the Midwest. Ranked among the top 20 cancer hospitals in the nation, The James is the 172-bed adult patient-care component of the cancer program at The Ohio State University. Source: Eileen Scahill Ohio State University Medical Center 07 December 2008 - Doctor Assisted Suicides Ruled As Legal By Montana Judge Judge Dorothy McCarter ruled that a Billings, Montana, man who has terminal cancer may legally undergo doctor-assisted suicide. The ruling may well be appealed as Montana state says the State, rather than the court, should decide on such issues - whether a terminally ill patient has the right to take his/her own life. The ruling makes Montana the third US state to allow terminally ill patients the legal choice of aid-in-dying, after Oregon and Washington. During the ruling the judge said "The Montana constitutional rights of individual privacy and human dignity, taken together, encompass the right of a competent terminally (ill) patient to die with dignity." The ruling added that a terminally-ill patient who finds his/her suffering to be 'unbearable' has the right to receive self-administered medication to hasten death. The ruling also stated that a doctor may prescribe such medication for the patient without fear of being taken to court for it. Dorothy McCarter wrote that not only does a patient have the right to die with dignity, but also his/her doctor needs protection from liability under the state's homicide laws. Mike McGrath, Attorney General, said his team of lawyers will discuss this ruling and will possibly appeal. He said doctor-assisted suicide is a constitutional issue and should be ruled on by the Supreme Court. Robert Baxter, 75, the terminally ill patient said "I am glad to know that the court respects my choice to die with dignity if my situation becomes intolerable." Baxter, a truck driver, suffers from lymphocytic leukemia. Compassion & Choices, a patient's right group, helped argue the case. Legal Director, Kathryn Tucker, said that the court found that it is the patients who should be given the right to make these critical decisions for themselves and their families - not the state. The State Attorney General's office said it was the responsibility of the state Legislature. As well as Baxter, the case included another four plaintiffs - doctors who need a ruling on whether they would face criminal charges if they assisted a patient with aid-in-dying. None of the doctors provide health care for Baxter. According to a press release by Compassion & Choices "The right to privacy, personal autonomy and dignity are deeply rooted in the political and cultural heritage of Montana. Establishing the right of terminally ill patients to seek aid in dying is well within the Montana tradition of living with dignity and personal responsibility. The case asserts that terminally ill, mentally competent Montanans have a protected right to choose aid in dying under the Montana State Constitution." The Montana Supreme Court reinforces living with dignity and personal responsibility saying, "We have chosen not to 'march lock-step' with the United States Supreme Court…we have held that Montana's unique constitutional language affords citizens (of Montana) a greater right to privacy." District Court Judge Jeffrey M. Sherlock wrote, "Montanans generally mind their own business and do not wish to restrict other people in their freedoms unless the exercise of those freedoms interferes with other members of society." (Compassion & Choices). Kathryn Tucker's 2007 Montana Law Review article provides more detail on the state's unusually strong protections for individual liberty, privacy, dignity and autonomy. "Such a case (as Baxter) asserts that mentally competent, terminally ill Montanans have a right protected under the Montana State Constitution's guarantees of privacy and dignity to chose to control their own deaths by obtaining medications from their physician for this purpose." (Compassion & Choices) -- Read Kathryn Tucker's Montana Law Review article (PDF) -- Click here to view the Baxter vs. Montana complaint (PDF) Written by Christian Nordqvist Copyright: Medical News Today Not to be reproduced without permission of Medical News Today 06 December 2008 - Bayer Announces Upcoming Presentations Of Campath(R) And Leukine(R) Data At The 50th Annual Meeting Of The American Society Of Hematology Bayer HealthCare Pharmaceuticals Inc. announced that data on Campath(R) (alemtuzumab) and Leukine(R) (sargramostim) will be presented at the 50th Annual Meeting of the American Society of Hematology (ASH) from December 6-9, 2008 in San Francisco, California. Clinical investigators from leading oncology and hematology research centers will present data through several oral and poster presentations reporting important findings in leukemia-related disorders, such as prognostic indicators for chronic lymphocytic leukemia (CLL) and side effects such as chemotherapy- induced neutropenia. Campath is indicated in the United States as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). Leukine is indicated for use following induction chemotherapy in patients 55 years and older with acute myelogenous leukemia (AML) to shorten the time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death. "We are pleased to see continued developments on both Campath and Leukine," said Pam Cyrus, Vice President, Medical Affairs, Oncology, Bayer HealthCare Pharmaceuticals. "These studies further demonstrate Bayer's ongoing commitment to supporting research to benefit the lives of people living with cancer." Abstracts are now available on the ASH Web site at http://www.hematology.org. Among the data that will be presented are the following: Campath: -- Poster 3164 (December 8, 5:30 p.m. PST) -- Clinical Outcome of B-Cell Chronic Lymphocytic Leukemia Following Alemtuzumab Therapy: Retrospective Study Within Various Cytogenetic Risk Categories -- Poster 329 (December 8, 12:00 p.m. PST) -- Subcutaneous Alemtuzumab (Campath) in Fludarabine- Refractory CLL: Final Results of the CLL2H Trial of the GCLLSG and Comprehensive Analysis of Prognostic Markers Leukine: -- Oral Presentation 665 (December 8, 3:30 p.m. PST) -- Comparison of Infection-Related Hospitalization Risk and Associated Costs Among Patients Receiving Sargramostim (Leukine), Filgrastim (Neupogen), and Pegfilgrastim (Neulasta) for Chemotherapy-Induced Neutropenia -- Poster 3173 (December 8, 5:30 p.m. PST) -- Experience with Fludarabine, Cyclophosphamide, Rituximab (FCR) Plus GM-CSF in Frontline Therapy for Chronic Lymphocytic Leukemia (CLL) About Campath Campath was the first monoclonal antibody approved by the United States Food and Drug Administration (FDA) for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). In September 2007, the FDA approved a supplemental Biologics License Application (sBLA) for Campath and granted regular approval for single-agent Campath for the treatment of B-CLL. Campath was initially approved in 2001 under accelerated approval regulations for the treatment of B-CLL in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Campath was developed by Genzyme Corporation. Campath is marketed in the U.S. by Bayer HealthCare Pharmaceuticals Inc., as Campath, and outside the United States as MabCampath(R). Important Safety Information WARNING: CYTOPENIAS, INFUSION REACTIONS, AND INFECTIONS -- Cytopenias: Serious, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia can occur in patients receiving Campath. Single doses of Campath greater than 30mg or cumulative doses greater than 90mg per week increase the incidence of pancytopenia. -- Infusion Reactions: Campath administration can result in serious, including fatal, infusion reactions. Carefully monitor patients during infusions and withhold Campath for Grade 3 or 4 infusion reactions. Gradually escalate Campath to the recommended dose at the initiation of therapy and after interruption of therapy for 7 or more days. -- Infections: Serious, including fatal, bacterial, viral, fungal, and protozoan infections can occur in patients receiving Campath. Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus infections. Campath is indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). Campath is administered as an IV infusion over two hours and should be dose escalated to recommended dose of 30 mg/day three times per week for 12 weeks. Patients are premedicated with oral antihistamine and acetaminophen prior to dosing. The most commonly reported adverse reactions are infusion reactions (fever, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), and infections (CMV viremia, CMV infection, other infections). In clinical trials, the frequency of infusion reactions was highest in the first week of treatment. Other commonly reported adverse reactions include vomiting, abdominal pain, insomnia and anxiety. The most commonly reported serious adverse reactions are cytopenias, infusion reactions, and immunosuppression/infections. See "Warnings and Precautions," and "Adverse Reactions" sections of full Prescribing Information. About Leukine Leukine is a growth factor that helps fight infection and disease in appropriate patients by enhancing immune cell function. Leukine was approved in the United States in 1991 and is marketed by Bayer HealthCare Pharmaceuticals. Leukine is the only growth factor approved in the U.S. for use following induction chemotherapy in older adults with acute myelogenous leukemia (AML) to shorten the time to neutrophil recovery and reduce the incidence of severe and life-threatening infections and infections resulting in death. Leukine also has been approved in the U.S. for use in four additional indications: myeloid reconstitution following allogeneic and autologous bone marrow transplantation (BMT), peripheral blood stem cell (PBSC) mobilization and subsequent myeloid reconstitution in patients undergoing PBSC transplantation, and bone marrow transplantation failure or engraftment delay. Leukine is available in two formulations, both of which are suitable for IV infusion and subcutaneous injection: -- Liquid: 500 mcg/mL sterile solution in multi-use vial -- Lyophilized powder: 250 mcg in single-use vial ready for sterile reconstitution Leukine has been used to treat nearly 250,000 cancer patients in the U.S. since 1991. Among its indications, Leukine is the only myeloid growth factor approved to reduce the incidence of infections resulting in early death following induction chemotherapy in older adults with AML. About Bayer HealthCare Pharmaceuticals Inc. Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals operation of Bayer HealthCare, an affiliate of Bayer AG. One of the world's leading, innovative companies in the healthcare and medical products industry, Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the United States, Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, General Medicine, Hematology/Neurology, and Oncology. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases. About Genzyme One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start- up to a diversified enterprise with more than 10,000 employees in locations spanning the globe and reported revenues in 2007 of $3.8 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation. With many established products and services helping patients in nearly 90 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as immune disease, infectious disease, and other areas of unmet medical need. Genzyme(R), Campath(R) and MabCampath(R) are registered trademarks of Genzyme Corporation. All rights reserved. Forward-looking Statements This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our annual and interim reports to the Frankfurt Stock Exchange and in our reports filed with the U.S. Securities and Exchange Commission (including our Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. Bayer HealthCare Pharmaceuticals Inc. http://www.pharma.bayer.com View drug information on Campath; Leukine. 04 December 2008 - Effects Of Childhood Cancer Treatment Increase Adult Survivors' Risk Of Osteoporosis Men who survived childhood leukemia treatment into adulthood were more likely to have low bone mineral density than other adults their age, putting them at risk of osteoporosis and bone fractures, according to a new study. The study, led by James G. Gurney, Ph.D., of the University of Michigan Comprehensive Cancer Center, found that 24 percent of the 74 survivors studied had abnormally low bone mineral density, a measure of the strength of bones. The average age of the survivors was 30, and they had been treated an average of 24 years ago for the most common type of childhood cancer, acute lymphoblastic leukemia. According to the World Health Organization, 11 percent of 30-year-old men and 19 percent of 30-year-old women on average have low bone mineral density, a condition known as osteopenia. In this study, published Dec. 1 in the journal Cancer, 36 percent of men and 16 percent of women had low bone mineral density. "Evaluations of bone health in childhood cancer survivors have only recently been noted as a concern. Routine monitoring has not yet become the standard of care for all survivors. Studies such as this one stress the importance of monitoring for bone health in these survivors, particularly since there may be some simple interventions, such as vitamin D and calcium, that may be beneficial," says study lead author Inas Thomas, M. D., an endocrinology fellow in the Department of Pediatrics at the U-M Medical School. Low bone mineral density can progress to osteoporosis, a bone disorder common in older adults that can lead to fractures. The researchers found that male survivors were more likely than female survivors to have lower bone mineral density, and shorter men and women were also more likely to have weaker bones. The researchers also looked at levels of growth hormones, which are known to be affected by leukemia treatment. Low growth hormone levels and low levels of another hormone called IGF-1 can contribute to poor bone health, but that they are not the only factors involved. The researchers believe the disease itself or the treatments such as radiation - particularly radiation to the brain - and chemotherapy may affect bone growth. "Survivors with known growth hormone deficiency or insufficiency should definitely be screened, but we would argue that all adult survivors should be screened as well. The disease, chemotherapy and cranial radiation - even if they do not lead to growth hormone deficiency - may play a role in the development of osteopenia or osteoporosis," Thomas says. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- Leukemia statistics: 5,240 Americans will be diagnosed with acute lymphoblastic leukemia this year and 1,460 will die from the disease, according to the American Cancer Society Additional authors: Janet E. Donohue, M.P.H., U-M Department of Pediatrics; Kirsten K. Ness, Ph.D., St. Jude Children's Research Hospital; Donald R. Dengel, Ph.D., University of Minnesota; K. Scott Baker, M. D., M.S., University of Minnesota Funding: National Institutes of Health Reference: Cancer, Vol. 113, issue 11, pp. 3248-3256, "Bone mineral density in young adult survivors of acute lymphoblastic leukemia" Source: Nicole Fawcett University of Michigan Health System 02 December 2008 - U.S FDA Grants Pralatrexate Orphan Drug Designation For The Treatment Of Patients With Follicular Lymphoma Allos Therapeutics, Inc. (Nasdaq:ALTH), a biopharmaceutical company focused on the development and commercialization of small molecule therapeutics for the treatment of cancer, today announced that the U.S. Food and Drug Administration (FDA) granted orphan drug designation to the Company's novel antifolate, pralatrexate (PDX), for the treatment of patients with follicular lymphoma. "We are pleased that the FDA has recognized the unmet medical need for effective new therapies for the treatment of patients with follicular lymphoma," said Paul L. Berns, President and Chief Executive Officer. "This designation further complements the orphan drug designation that the FDA previously awarded to pralatrexate in patients with T-cell lymphoma and diffuse large B-cell lymphoma." The U.S. Orphan Drug Act is intended to assist and encourage companies to develop safe and effective therapies for the treatment of rare diseases and disorders. Under the Orphan Drug Act, the FDA will not accept or approve other marketing applications from other sponsors to market the identical active moiety for the same therapeutic indication for a seven-year period once a designated orphan drug is approved for marketing. In addition to potential market exclusivity, orphan drug designation provides potential protocol assistance, advice on the conduct of clinical trials, tax credits for clinical research expenses, grant funding for research of rare disease treatments and waiver of the Prescription Drug User Fee Act (PDUFA) filing fee for the drug's sponsor. About Pralatrexate (PDX) Pralatrexate is a novel, small molecule chemotherapeutic agent that inhibits dihydrofolate reductase, or DHFR, a folic acid (folate)-dependent enzyme involved in the building of nucleic acid, or DNA, and other processes. Pralatrexate was rationally designed for efficient transport into tumor cells via the reduced folate carrier, or RFC-1, and effective intracellular drug retention. The Company believes these biochemical features, together with preclinical and clinical data in a variety of tumors, suggest that pralatrexate may have a favorable safety and efficacy profile relative to methotrexate and other related DHFR inhibitors. The Company believes pralatrexate has the potential to be delivered as a single agent or in combination therapy regimens. About Allos Therapeutics, Inc. Allos Therapeutics is a biopharmaceutical company focused on developing and commercializing small molecule therapeutics for the treatment of cancer. The Company's lead product candidate, pralatrexate (PDX), is a novel antifolate currently under evaluation in a pivotal Phase 2 (PROPEL) trial in patients with relapsed or refractory peripheral T-cell lymphoma. The PROPEL trial is being conducted under an agreement reached with the U.S. Food and Drug Administration under its special protocol assessment, or SPA process. The Company is also investigating pralatrexate in patients with non-small cell lung cancer, bladder cancer and a range of lymphoma subtypes. The Company's other product candidate is RH1, a targeted chemotherapeutic agent currently being evaluated in a Phase 1 trial in patients with advanced solid tumors or non-Hodgkin's Lymphoma (NHL). The Company currently retains exclusive worldwide rights to pralatrexate and RH1 for all indications. For additional information, please visit the Company's website at http://www.allos.com. Safe Harbor Statement This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding the potential safety and efficacy profile of pralatrexate for the treatment of lymphoma or any other type of cancer and other statements that are other than statements of historical facts. In some cases, you can identify forward-looking statements by terminology such as "may," "will," "should," "expects," "intends," "plans," "anticipates," "believes," "estimates," "predicts," "projects," "potential," "continue," and other similar terminology or the negative of these terms, but their absence does not mean that a particular statement is not forward-looking. Such forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated by the forward-looking statements. These risks and uncertainties include, among others: that the Company may experience delays in the completion of clinical trials, whether caused by adverse events, regulatory issues or other factors; that clinical trials may not demonstrate that pralatrexate is both safe and effective for the treatment of patients with lymphoma, relapsed or refractory PTCL, or any other type of cancer; that data from preclinical studies and clinical trials may not necessarily be indicative of future clinical trial results; that the safety and/or efficacy results of clinical trials for pralatrexate will not support an application for marketing approval in the United States or any other country; and that the Company may lack the financial resources and access to capital to fund future clinical trials for pralatrexate or any of its other product candidates. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the Company's Annual Report on Form 10-K for the year ended December 31, 2007 and in the Company's other periodic reports and filings with the Securities and Exchange Commission. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. All forward-looking statements are based on information currently available to the Company on the date hereof, and the Company undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this presentation, except as required by law. Allos Therapeutics, Inc. ===== 29 November 2008 - Researchers Identify Genomic Causes Of A Certain Type Of Leukemia Relapse Scientists at St. Jude Children's Research Hospital have identified distinctive genetic changes in the cancer cells of children with acute lymphoblastic leukemia (ALL) that cause relapse. The finding offers a pathway to designing treatments for ALL relapse in children and, ultimately, in adults. The most common childhood cancer, ALL affects thousands of children annually in the United States. Although more than 80 percent of ALL cases are cured, relapse is a significant problem, with only 30 percent of children with relapsed ALL surviving. Previous studies had found some evidence for genetic differences between the cancer cells of ALL patients at initial diagnosis and those who relapsed. That information was limited, and there had never been a broad comparison of the entire genomes of ALL at initial diagnosis and at subsequent relapse. In the study that appears in the Nov. 28, 2008, issue of the journal Science, St. Jude researchers compared the genomes of the cancer cells of 61 childhood ALL patients when they were initially diagnosed and after they had relapsed. The investigators used millions of genetic marker characteristic genetic variations called single nucleotide polymorphisms as guideposts to pinpoint genetic changes characteristic of relapsed cells. Using these genetic markers, the researchers analyzed all of the cells' chromosomes to look for genetic changes called copy number abnormalities specific to relapsed cells. These changes are considered a major type of damaging gene alterations in ALL. "In more than 90 percent of the cases, we found differences in the genetic alterations present at the time of diagnosis and at the time of relapse," said Charles Mullighan, M.D., Ph.D., assistant member in the St. Jude Department of Pathology and the paper's first author. "Examining the new changes that are arising at relapse tells us a lot about the individual genetic lesions that might confer resistance to treatment and be responsible for relapse." According to the researchers, the relapse-related genetic changes commonly disrupted the machinery by which white blood cells called B cells mature and proliferate. Importantly, the relapse-related genetic changes only infrequently involved genes directly regulating the responsiveness to anti-cancer drugs. The analysis also indicated that in most cases, the cancer cells responsible for relapse were related to those that originally gave rise to the cancer. Those relapse cells were present at low levels at diagnosis, the scientists' analysis indicated. However, in a few cases, the relapse cells evolved from genetically distinct cells, indicating that the relapsed leukemia was actually an entirely new cancer. "The key finding in our work is that in the majority of cases, relapse is arising from a cell already present at the time of diagnosis," said James Downing, M.D., St. Jude Scientific Director, chair of the Department of Pathology and the paper's senior author. "That cell is selected for during treatment and then subsequently emerges as basis for relapse." "The second key point is that we have found a large number of new genetic alterations that had not been previously identified as new targets of copy number changes at the time of relapse," Mullighan added. Mullighan emphasized that the findings do not mean immediate treatments for ALL relapse. "But, this is a very important starting point because we have identified several key pathways that are the most common targets of new genetic changes at the time of relapse," he said. Identification of these relapse pathways will lead to understanding of the biological machinery of relapse, and ultimately to drugs that target that machinery. Such studies of the relapse machinery are now underway at St. Jude. In other further studies, the researchers are also looking for other relapse-related genetic alterations besides copy number abnormalities. They are also applying their findings to adult ALL, in which relapse is a more significant problem than in the childhood disease. Other authors of this paper include Letha Phillips, Xiaoping Su, Jing Ma, Christopher Miller and Sheila Shurtleff. The research was supported in part by the National Health and Medical Research Council of Australia and ALSAC. St. Jude Children's Research Hospital St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. St. Jude Children's Research Hospital 332 N Lauderdale St., Mail Stop 761 Memphis TN 38122 United States http://www.stjude.org 25 November 2008 - FDA Grants Pralatrexate Orphan Drug Designation For The Treatment Of Patients With Diffuse Large B-Cell Lymphoma Allos Therapeutics, Inc. (Nasdaq: ALTH), a biopharmaceutical company focused on the development and commercialization of small molecule therapeutics for the treatment of cancer, today announced that the U.S. Food and Drug Administration (FDA) granted orphan drug designation to the Company's novel antifolate, pralatrexate (PDX), for the treatment of patients with diffuse large B-cell lymphoma. "We are pleased with this designation, which highlights the need for novel therapies to treat lymphoma," said Paul L. Berns, President and Chief Executive Officer. "Pralatrexate previously received orphan drug designation from the FDA for the treatment of patients with T-cell lymphoma. This additional designation reinforces our intention to further evaluate pralatrexate as a potential treatment for patients with B-cell lymphoma." The U.S. Orphan Drug Act is intended to assist and encourage companies to develop safe and effective therapies for the treatment of rare diseases and disorders. Under the Orphan Drug Act, the FDA will not accept or approve other marketing applications from other sponsors to market the identical active moiety for the same therapeutic indication for a seven-year period once a designated orphan drug is approved for marketing. In addition to potential market exclusivity, orphan drug designation provides potential protocol assistance, advice on the conduct of clinical trials, tax credits for clinical research expenses, grant funding for research of rare disease treatments and waiver of the Prescription Drug User Fee Act (PDUFA) filing fee for the drug's sponsor. About Pralatrexate (PDX) PDX is a novel, small molecule chemotherapeutic agent that inhibits dihydrofolate reductase, or DHFR, a folic acid (folate)-dependent enzyme involved in the building of nucleic acid, or DNA, and other processes. PDX was rationally designed for efficient transport into tumor cells via the reduced folate carrier, or RFC-1, and effective intracellular drug retention. The Company believes these biochemical features, together with preclinical and clinical data in a variety of tumors, suggest that PDX may have a favorable safety and efficacy profile relative to methotrexate and other related DHFR inhibitors. The Company believes PDX has the potential to be delivered as a single agent or in combination therapy regimens. About Allos Therapeutics, Inc. Allos Therapeutics is a biopharmaceutical company focused on developing and commercializing small molecule therapeutics for the treatment of cancer. The Company's lead product candidate, pralatrexate (PDX), is a novel antifolate currently under evaluation in a pivotal Phase 2 (PROPEL) trial in patients with relapsed or refractory peripheral T-cell lymphoma. The PROPEL trial is being conducted under an agreement reached with the U.S. Food and Drug Administration under its special protocol assessment, or SPA process. The Company is also investigating pralatrexate in patients with non-small cell lung cancer, bladder cancer and a range of lymphoma subtypes. The Company's other product candidate is RH1, a targeted chemotherapeutic agent currently being evaluated in a Phase 1 trial in patients with advanced solid tumors or non-Hodgkin's Lymphoma (NHL). The Company currently retains exclusive worldwide rights to pralatrexate and RH1 for all indications. For additional information, please visit the Company's website at http://www.allos.com. Safe Harbor Statement This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding the potential safety and efficacy profile of pralatrexate for the treatment of lymphoma or any other type of cancer and other statements that are other than statements of historical facts. In some cases, you can identify forward-looking statements by terminology such as "may," "will," "should," "expects," "intends," "plans," anticipates," "believes," "estimates," "predicts," "projects," "potential," "continue," and other similar terminology or the negative of these terms, but their absence does not mean that a particular statement is not forward-looking. Such forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated by the forward-looking statements. These risks and uncertainties include, among others: that the Company may experience delays in the completion of clinical trials, whether caused by adverse events, regulatory issues or other factors; that clinical trials may not demonstrate that pralatrexate is both safe and effective for the treatment of patients with lymphoma, relapsed or refractory PTCL, or any other type of cancer; that data from preclinical studies and clinical trials may not necessarily be indicative of future clinical trial results; that the safety and/or efficacy results of clinical trials for pralatrexate will not support an application for marketing approval in the United States or any other country; and that the Company may lack the financial resources and access to capital to fund future clinical trials for pralatrexate or any of its other product candidates. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the Company's Annual Report on Form 10-K for the year ended December 31, 2007 and in the Company's other periodic reports and filings with the Securities and Exchange Commission. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. All forward-looking statements are based on information currently available to the Company on the date hereof, and the Company undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this presentation, except as required by law. Allos Therapeutics, Inc. 20 November 2008 - Lymphoma Association Launches New Short Film The Lymphoma Association is delighted to launch their latest short film which shows the services they offer to anyone affected by lymphoma - the UK's sixth most common cancer. The charity were selected to have the film made for them for a nominal fee by the Media Trust, an organisation which helps charities raise awareness by providing them with volunteers from the TV, film and video industry who then produce videos for them. Julie Mercer, Head of Communications for the Lymphoma Association said: "We're absolutely delighted with the film which details our services from the perspective of those people who have used them. Three of our supporters kindly agreed to share the details of their own lymphoma journeys in order to offer support to others affected by the disease." To take a look at the film, visit http://www.lymphomas.org.uk Source Lymphoma Association http://www.lymphomas.org.uk 11 November 2008- Researchers Aim To Over-stress Already Taxed Mantle Cell Lymphoma Cells Cancer cells are already stressed by the fast pace they require to grow and spread and scientists believe a little more stress just may kill them. "Think about an assembly line in a factory that is working five times faster than normal," said Dr. Kapil Bhalla, director of the Medical College of Georgia Cancer Center. "There is a lot of stress but you need workers to keep going. Some of them fall out, some get bent out of shape." His research team believes they can disrupt the over-stressed assembly line of mantle cell lymphoma and possibly similar cancers such as pancreatic, liver and breast, by taking away support needed for rapid protein turnover and by clogging up the mechanism for eliminating poorly made ones. Mantle cell lymphoma, an aggressive cancer of the lymphatic system that mostly occurs in middle age, responds initially to chemotherapy and antibiotics, but often returns, said Dr. Bhalla. Patients have a median survival of three to four years. This cancer affects b lymphocytes, immune cells which make antibodies to fight infection. Ironically, in the process of rearranging genes to make antibodies to a specific invader, mistakes happen, and a would-be protector becomes cancer. MCG researchers found that to keep their fast pace, these now-malignant cells need increased activity of heat shock protein 90. "Cancer cells require hsp90 for keeping their proteins in active conformation to do their job. That is what cancer is addicted to," said Dr. Bhalla, Cecil F. Whitaker, Jr., M.D./Georgia Research Alliance Eminent Scholar in Cancer and Georgia Cancer Coalition Distinguished Cancer Scholar. Hsp90 is one of the more common molecular chaperones, which help proteins get made, moved, folded and function. Its levels and activity are upregulated in response to stress. They also found that the usually busy endoplasmic reticulum of these cells, which is supposed to be making normal antibodies, is stressed by making hyperactive, cancer-associated proteins. Stepped-up protein production also means more misfolded proteins that the proteasome must deal with. "It's all stressed-out machinery," Dr. Bhalla said. To help push cancer cells over the edge, the researchers are inhibiting hsp90, so the cells lose the molecular chaperone function required to maintain their fast pace. This also puts more stress on the endoplasmic reticulum. Independently hsp90 inhibitors are known to selectively kill cancer cells. But researchers also are clogging up the proteasome, the machinery for chopping up misfolded proteins, recycling some products and eliminating what's left. Much like a sink won't work with a clogged garbage disposal, mantle cell lymphoma cells will start backing up. When a cell detects excessive misfolded proteins, it first has a protective response, but if the problem persists, it commits suicide. With support from a five-year, $1.5 million grant from the National Cancer Institute, the researchers are using hsp90 and proteasome inhibitors to study protective versus lethal endoplasmic reticulum stress as a way to get rid of mantel cell lymphoma cells. The laboratory studies are being done in human mantle cell lymphoma cells as well as an animal model the researchers developed. The drugs they are using already are in early clinical trials for a variety of cancers but have not yet been packaged together, Dr. Bhalla said. "We kill cancer cells and a lot of them with this strategy." Still, at least one more inhibitor may get added to the mix. After the rather brutal attack at the cancer's molecular underpinnings, the immune system comes in to essentially mop the floor, but researchers have found cancer cells can still get a pass from an enzyme called IDO. A team of MCG researchers led by Dr. David Munn is exploring IDO's therapeutic potential in cancer. Fetuses use IDO to avoid rejection by the mother's immune system and tumors appear to use it as well. Dr. Bhalla suspects an IDO inhibitor, already under study for lung cancer and other tumors, likely will get a shot at mantle cell lymphoma as well. Medical College of Georgia 09 November 2008 - Recommendations For Women To Improve Their Quality Of Life After Breast Cancer Treatment Opting for less damaging treatments, staying active and learning about the warning signs of lymphedema: that's how women with breast cancer can avoid developing chronic lymphedema, according to the German Institute for Quality and Efficiency in Health Care (IQWiG). Women can learn more about how to protect themselves from this common and distressing adverse effect of treatment as well as handle the condition at the Institute's website, http://www.informedhealthonline.org/. Protecting women's lymph systems Breast cancer treatment is becoming more effective, with a survival rate of more than 80% for this disease in Germany. As the survival rate goes up, quality of life for survivors assumes even more importance, according to the German Institute. Lymphedema is an adverse effect of breast cancer treatment caused by damage to the lymph system. When the lymph system cannot properly remove fluids from around the breast and arm, the fluid gathers and the arm swells. This causes pain and restricts movement. It could become a chronic problem that is hard to treat. The more aggressive breast cancer treatment is, the higher the risk of lymphedema. Researchers estimate around 400,000 women in Germany alone have lymphoedema caused by breast cancer treatment. "Even with many women having less aggressive breast cancer treatments, around 10 to 20% will develop lymphedema," according to Professor Peter Sawicki, the Institute's Director. "We doctors still underestimate the impact on patients' quality of life of treatment adverse effects like lymphedema. The first step to prevention is using therapies that limit the damage to the woman's lymph system." Better quality of life after breast cancer The second step to better quality of life is to stay active. For years, there were many warnings to women to limit the use of the arm and be careful about being too active after breast cancer treatment. But Professor Sawicki said, "While women who are developing lymphedema have to protect their arms more, the blanket warnings from the past to all women with breast cancer were never based on strong scientific evidence. In fact, trials of exercise in women with breast cancer have shown that it can improve quality of life without increasing the risk of lymphedema." However women need to learn about the warning signs of lymphedema and act early. "A feeling of heaviness, heat and swelling in the arm - women need to take action early when this happens in the years after breast cancer treatment," Professor Sawicki said. "Lymphedema is easier to treat effectively in the early stages." The treatment shown to be effective in trials is compression therapy with bandages or compression sleeves. A special massage technique called lymphatic drainage as well as physiotherapy might be able to help, but this has not been so well-studied. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- This release is available in German. The Institute's website, http://www.informedhealthonline.org/, provides the public with easy-to-understand information about current medical developments and research on important health issues. If you would like to be kept up-to-date with the latest publications on the independent health information website, you can subscribe to the informedhealthonline.org newsletter. Information - Lymphedema: http://www.informedhealthonline.org/a-z-list.556.56.en.html Source for data on lymphedema in Germany: Seifart U, Albert U-S, Helm M-E, Hübner J et al. [Lymphedema in patients with breast cancer--a consensus regarding diagnostics and therapy in patients with postoperative lymphedema after primary breast cancer.] Rehabilitation (Stuttg) 2007; 46: 340-348. Source: Hilda Bastian Institute for Quality and Efficiency in Health Care 30 October 2008 - Patient Strategies Identified For Managing Symptoms Of Lymphedema An estimated 2 million women in the United States are at risk of developing lymphedema, a condition that involves the chronic and abnormal swelling of the arm, chest, neck and/or back, as a complication of breast cancer treatment. While physicians will recommend proven techniques to manage the swelling, a University of Missouri researcher has found that patients often won't follow the recommendations, or they will use alternative treatments and not discuss them with their doctors. "Lymphedema has a profound impact on health and well-being, but often goes undiagnosed and untreated by physicians and patients," said Jane Armer, professor in the Sinclair School of Nursing and director of nursing research at the Ellis Fischel Cancer Center. "Understanding the ways that people self-manage the chronic symptoms of lymphedema is essential to facilitate an improvement in the use of treatments and the quality of life of these people." Armer surveyed breast cancer survivors with lymphedema about their practices for managing symptoms, including swelling and heaviness. She found the most common strategy was to not treat the symptom. For 12 out of 14 symptoms, patients reported taking no action 29 percent to 65 percent of the time. This finding is consistent with Armer's conclusions from a previous study. "Considering the entire lymphedema population (not just breast cancer survivors), the percentage of patients who treat their symptoms is probably even lower," Armer said. "Data have shown that breast cancer survivors are more proactive in seeking information for self-care, and they are more likely to follow a daily self-care plan for lymphedema than those who developed lymphedema for a different reason." Armer found that patients who choose to treat their symptoms use a variety of techniques, which can be divided into three main groups. The first group includes recommended management techniques, non- pharmaceutical strategies typically recommended by physicians, including manual lymphatic drainage, compression garments and elevation. Patients use these techniques most often, or 47 percent of the time. The second group was pharmaceutical treatments including the use of medications both prescription (antibiotics) and over-the-counter (pain medication and cortisone cream). The final group was lay symptom management techniques, strategies not necessarily recommended by health care professionals but common sense, folk, complementary or alternative methods. According to Armer, patients increasingly are using lay therapies, but less than 40 percent report discussing their use of complementary therapies with a doctor. Previous research has found these unconventional therapies are generally not taught at medical schools or are unavailable at most hospitals. "While lay symptom management is undoubtedly an important form of health care, the discrepancy between the use of self-care treatments and doctor-recommended treatments for lymphedema must be addressed," Armer said. "It's important for health care professionals to recognize the scope and diversity of practices that breast cancer survivors choose when managing their symptoms. Continued research of this issue can help develop effective management techniques to be incorporated into standards of practice for physicians and patients." The Lymphedema Research Project at Ellis Fischel and Sinclair School of Nursing provides research opportunities for breast cancer survivors to participate in oncology nursing research. The studies are funded by the Lance Armstrong Foundation and the National Institutes of Health. MU researchers maintain a database of participants for future studies; interested participants for breast cancer and/or lymphedema research may submit their contact information and will be contacted if they meet the criteria for current or new studies. Friends, family members and co-workers who have not had breast cancer or lymphedema also may enroll for studies that require matched control participants. "We are experiencing great success by connecting participants to studies through our database. It gives people an opportunity to contribute to breast cancer research and allows our research efforts to continue," Armer said. "A critical next step in lymphedema research is the rigorous evaluation of the effectiveness of self-management techniques." ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- The study, "Self-Reported Management of Breast Cancer-Related Lymphoedema," was published in the Journal of Lymphoedema. Additional information about lymphedema research at MU Source: Emily Smith University of Missouri-Columbia 21 October 2008 - Non-Hodgkin Lymphoma Patients' Survival Affected By Socioeconomic And Treatment Factors Socioeconomic factors and the type of treatment received have an impact on a non-Hodgkin lymphoma (NHL) patient's risk of dying. That is the finding of a new study published in the December 1, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society. The study reveals that poorer socioeconomic status increases a patient's risk of dying, while receiving chemotherapy reduces the risk. NHL is a common type of cancer in the elderly. Its incidence has been increasing over the past several decades, and Caucasians have higher incidence and death rates related to the disease than patients in other ethnic groups. Newer treatments for NHL have become available in recent years; however, studies have not addressed ethnic disparities in survival as they relate to treatment, diagnosis, socioeconomic status, or other factors. To investigate the issue, Dr. Xianglin Du of the University of Texas School of Public Health in Houston and colleagues analyzed SEER (Surveillance, Epidemiology and End Results)-Medicare linked data for more than 13,000 patients diagnosed at age 65 or older between 1992 and 1999. The metropolitan areas of San Francisco/Oakland, Detroit, Atlanta, Seattle, Los Angeles County, San Jose/Monterey, and the states of Connecticut, Iowa, New Mexico, Utah, and Hawaii were included in this study. Dr. Du and his team analyzed data related to survival, socioeconomic status, treatment (chemotherapy or radiation), tumor factors (stage and type of NHL), the presence of other diseases or conditions, and other characteristics such as age, race, marital status, and geographic area. The investigators found that receiving chemotherapy was associated with prolonged survival in patients with NHL and that elderly Caucasian patients with NHL were more likely to receive chemotherapy (52.4 percent) compared with African-Americans (43.2 percent). Also, poor socioeconomic status was significantly associated with increased risk of mortality, and there were a larger proportion of African- American patients living in poor communities compared with other ethnicities. No significant differences in the risk of death were seen between African-Americans and Caucasians after controlling for factors such as treatment and socioeconomic status. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- Article: "Ethnic variations in diagnosis, treatment, socioeconomic status and survival in a large population- based cohort of elderly patients with Non-Hodgkin's Lymphoma." Michael Wang, Keith D. Burau, Shenying Fang, Harry Wang, and Xianglin L. Du. CANCER; Published Online: October 20, 2008 (DOI: 10.1102/cncr.23914); Print Issue Date: December 1, 2008. Source: David Sampson American Cancer Society 20 October 2008 - Discovery Of A Gene Critical For Development Of Lymphatic System, Implications For Cancer And Lymphatic Disorders Treatment Researchers have identified a gene critical for the development of the lymphatic system in a discovery that will have implications for treatment of cancer and lymphatic disorders and other diseases. The team, led by Professor Peter Koopman and Dr Mathias François from the Institute for Molecular Bioscience at The University of Queensland (UQ), found that a single gene - Sox18 - triggers the development of the lymphatic vessels. "The rate at which new lymphatic vessels can form is thought to be one of the key factors in determining how quickly a tumour can spread and thus how severely a patient will be affected by cancer," Professor Koopman said. "The lymphatic vessels also play a central role in maintaining fluid balance in the body and carrying infection- fighting white blood cells, so greater knowledge about the lymphatic system can offer insights and suggest therapies for a range of diseases." The team made the discovery, reported today (Monday, October 20) in leading science journal Nature, by examining mice in which Sox18 had been inactivated. They found that the development of lymphatic vessels was massively disrupted. "We suspected Sox18 might play a critical role in lymphatic vessel formation after observing that mice with one inactivated copy of the gene displayed similar symptoms to humans with a genetic condition that affects the lymphatic system, known as HLT," Professor Koopman said. "It turns out that Sox18 has a much more important role than we first thought - in fact, it's the master controller of lymphatic vessel development." The team will now focus on finding genes regulated by Sox18 and determining how this regulation occurs, which may suggest ways of promoting or preventing lymphatic vessel formation. "If we know how to prevent lymphatic vessels from forming, then we will be a lot closer to halting the spread of tumours through the body. Conversely, if we know how to stimulate the formation of these vessels, then it might be possible to treat diseases such as lymphedema," Professor Koopman said. Lymphedema occurs when the lymphatic vasculature is impaired, causing a build-up of fluid in part of the body, which leads to painful and dangerous swelling of that body part, and, if left untreated, deformity. The discovery was the result of three years of research by an international team of scientists from Australia, Italy and Hong Kong, led by UQ and supported by a number of organisations including the Australian Cancer Research Foundation, the National Health and Medical Research Council of Australia, the Heart Foundation of Australia, and the Australian Research Council. The University of Queensland, Brisbane Australia http://www.uq.edu.au 17 October 2008 - Journal Of Clinical Investigation Online Early Table Of Contents: Oct. 16, 2008 The sperm that successfully fertilizes an egg triggers a series of events, known collectively as egg activation, that are considered the first step in the initiation of embryo development. Detection of egg activation is used by clinics to determine whether an in vitro fertilization procedure (a process whereby egg cells are fertilized by sperm in a test tube) has been successful. The sperm of some patients who repeatedly fail the in vitro fertilization technique ICSI, which is used to treat male factor infertility, fail to induce egg activation, and the patients are therefore sterile. Rafael Fissore and colleagues, at the University of Massachusetts, Amherst, have now uncovered one molecular defect underlying such sterility: the sperm lack detectable levels of the protein PLC, zeta-1. TITLE: Human sperm devoid of PLC, zeta 1 fail to induce Ca2+ release and are unable to initiate the first step of embryo development AUTHOR CONTACT: Rafael A. Fissore University of Massachusetts, Amherst, Massachusetts, USA. View the PDF of this article at: https://www.the-jci.org/article.php?id=36942 ONCOLOGY: Take it down a Notch(1): new role for Notch1 in facilitating melanoma development One of the most aggressive forms of cancer is a type of skin cancer known as melanoma. Melanomas are the least common type of skin cancer but account for the majority of deaths from skin cancer, in part because they are resistant to most conventional therapies (chemotherapies and radiation treatment). Marianne Broome-Powell and colleagues, at Stanford University, have previously found that a shortage of oxygen (hypoxia) in the skin contributes to the development of melanomas in conjunction with activation of a signaling protein known as Akt. Now, however, using human melanoma samples and cells lines as well as a xenograft model of melanoma development, they have identified another signaling protein that is required for Akt and hypoxia to cause melanoma development, Notch1. These data suggest that targeting the Notch signaling pathway might provide a new therapeutic approach to treating melanoma. TITLE: Notch1 is an effector of Akt and hypoxia in melanoma development AUTHOR CONTACT: Marianne Broome Powell Stanford University, Stanford, California, USA. View the PDF of this article at: https://www.the-jci.org/article.php?id=36157 INFLAMMATION: Platelets go with their gut feeling, helping promote intestinal inflammation Sean Colgan and colleagues, at the University of Colorado Denver School of Medicine, Aurora, have provided new insight into the function of nonimmune blood cells known as platelets in the inflamed intestine, and suggest that platelets might help promote bacterial clearance under inflammatory conditions. In the study, platelets were found to be able to efficiently cross a monolayer of epithelial cells (the cells that line the intestine) only when immune cells known as PMNs were also present and able to cross. Similar comigration of platelets and PMNs was observed in intestinal tissue from human patients with inflammatory bowel disease. Further studies, in vitro and in a mouse model of intestinal inflammation, indicated that platelets that crossed the epithelial cells triggered epithelial cell secretion of chloride ions, and therefore water, into the intestine. The mechanism underlying this effect was shown to involve platelet release of large amounts of ATP, which was then broken down to adenosine (the molecule responsible for triggering epithelial cell secretion of chloride ions) by proteins such as CD73 and ecto-NTPDases on the surface of epithelial cells. TITLE: PMNs facilitate translocation of platelets across human and mouse epithelium and together alter fluid homeostasis via epithelial cell-expressed ecto-NTPDases AUTHOR CONTACT: Sean P. Colgan University of Colorado Denver School of Medicine, Aurora, Colorado, USA. View the PDF of this article at: https://www.the-jci.org/article.php?id=35874 METABOLIC DISEASE: The protein ABCG1 helps keep cells lining blood vessels healthy One of the main causes of heart attack and stroke is a disease known as atherosclerosis (sometimes simply referred to as hardening of the arteries), which affects the major arterial blood vessels. One predictor of an individual's risk of developing atherosclerosis is the level of the molecule HDL in the blood, high levels have a protective effect. New data, generated in mice, by Naoki Terasaka and colleagues, at Columbia University College of Physicians and Surgeons, New York, have provided new insight into the atheroprotective effects of HDL: they ensure that the cells lining the major arterial blood vessels (endothelial cells) are able to continue functioning as normal. In the study, arteries from mice lacking the protein ABCG1 and from mice lacking both ABCA1 and ABCG1 showed decreased endothelial cell-dependent functions when they were analyzed after the mice had been fed a diet that induces atherosclerosis. Further analysis revealed that endothelial cells from these mice had specific molecular defects, including an accumulation of cholesterol and cholesterol-related molecules. A similar role for ABCG1 in preventing the accumulation of cholesterol within cells was observed when human aortic endothelial cells were analyzed. Furthermore, treatment of these human cells with HDL prevented the accumulation of cholesterol in an ABCG1-dependent manner. As ABCG1 is known to promote the efflux of cholesterol from other cell types in a process that involves HDL, the authors suggest that ABCG1 and HDL maintain the function of endothelial cells in mice fed a diet that induces atherosclerosis, in part by promoting the efflux of cholesterol and other related fats. TITLE: ABCG1 and HDL protect against endothelial dysfunction in mice fed a high-cholesterol diet AUTHOR CONTACT: Naoki Terasaka Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. View the PDF of this article at: https://www.the-jci.org/article.php?id=35470 VASCULAR BIOLOGY: O-glycan control of lymphatic vessel development Molecules known as O-glycans have an essential role in embryonic vascular development, but the cell type in which they need to be expressed has not been determined. Now, however, Lijun Xia and colleagues, at Oklahoma Medical Research Foundation, Oklahoma City, have found that O-glycans in endothelial cells (the cells that line blood and lymphatic vessels) are required for lymphatic vessel development in mice. The authors generated mice lacking T-synthase, a protein critical for making O-glycans, in endothelial cells and blood cells (EHC T-syn-/- mice). Most EHC T-syn-/- mice died in utero or soon after birth, and death was associated with disorganized and blood-filled lymphatic vessels caused by abnormal connections between blood and lymphatic vessels. Mechanistic insight was provided by the observation that levels of the molecule podoplanin were decreased in EHC T-syn-/- ECs and that mice lacking podoplanin exhibited similar lymphatic vessel defects to EHC T-syn-/- mice. Thus, the separation of blood and lymphatic vessels during embryonic development seems to be controlled by endothelial cell O-glycans, in part through their ability to regulate podoplanin expression. Further, as postnatal deletion of the gene encoding T-synthase also caused abnormal connections between blood and lymphatic vessels, the same mechanism is likely to be operational in adult mice. TITLE: Endothelial cell O-glycan deficiency causes blood/lymphatic misconnections and consequent fatty liver disease in mice AUTHOR CONTACT: Lijun Xia Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- Source: Karen Honey Journal of Clinical Investigation 17 October 2008 - Landmark Study Demonstrates Potential Of Radioimmunotherapy For Treatment Of Indolent B-Cell Non-Hodgkin's Lymphoma Cell Therapeutics, Inc. (CTI) (Nasdaq and MTA: CTIC) announced that the Journal of Clinical Oncology has published the results of the First-line Indolent Trial (FIT) demonstrating that use of Zevalin(R)([90Y]- ibritumomab tiuxetan) in consolidation therapy after remission induction in previously untreated patients with follicular non-Hodgkin's lymphoma provided important patient benefits including a significant improvement in progression free survival. A companion editorial discussed the growing evidence for the efficacy of radioimmunotherapy (RIT) in B-cell lymphomas. Cell Therapeutics has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for use of Zevalin in first-line consolidation therapy based on the FIT data. Oliver W. Press, M.D., Ph.D., Member of the Fred Hutchinson Cancer Research Center and Professor at the University of Washington, commented in his editorial that the studies "confirm and extend prior data demonstrating the tremendous potential of RIT in the treatment of B-cell NHL at diagnosis and after relapse at both conventional and myeloablative doses. Despite the overwhelming body of evidence, however, RIT remains underused in the United States and other countries. The reasons for this underuse have been widely debated but seem to be related, at least partially, to logistic issues involved in the transfer of care from the hematologist/oncologist to the nuclear medicine physician, concerns about inadequate reimbursement by Medicare for RIT, and exaggerated emphasis on delayed effects such as marrow damage and secondary malignancies. It is hoped that studies such as those in this issue would encourage wider appreciation and use of RIT." "We couldn't agree more with Dr. Press' comments about the importance of these results for patients with newly diagnosed follicular NHL as well as his views as to why this important therapeutic option is underutilized by physicians," noted James Bianco, M.D., CEO of Cell Therapeutics. "We have been working with CMS in making reimbursement for RIT similar as any biologic agent, and with the FDA on reviewing the FIT results for a potential indication as consolidation therapy following first-line therapy in newly diagnosed patients as well as removing the need for the pre-treatment nuclear medicine scan on the basis of studies such as FIT and accumulated safety data. We believe these steps will allow office based hematologist/oncologists the ability to offer RIT with Zevalin to their patients eliminating many of the current concerns that have limited patient access to this important treatment option." The multinational, randomized phase III First-line Indolent Trial (FIT) evaluated the benefit and safety of a single infusion of Zevalin in 414 patients with CD20-positive follicular non-Hodgkin's lymphoma who had achieved a partial response or a complete response after receiving a variety of first-line chemotherapy regimens. The FIT trial demonstrated that when used as a first-line consolidation therapy for patients with follicular non-Hodgkin's lymphoma, Zevalin significantly improved the median progression-free survival time from 13.3 months (control arm) to 36.5 months (Zevalin arm) (p<0.0001). This advantage was observed regardless of whether patients were in partial remission (29.3 v 6.2 months p<0.0001 without Zevalin) or complete remission (53.9 v 29.5 months p=0.0154). Furthermore, Zevalin consolidation converted 77 percent of patients who had achieved only a partial remission (PR) after induction therapy to complete remission / complete remission unconfirmed (CR/CRu). Nearly all subgroups appeared to benefit regardless of prognostic score. The primary investigators of the study concluded that Zevalin consolidation of first remission in advanced stage follicular non-Hodgkin's lymphoma is highly effective, resulting in a total complete response (CR + CRu) rate of 87 percent and prolongation of median progression-free survival (PFS) by approximately two years, with a toxicity profile comparable to that seen with Zevalin's use in approved indications. Zevalin- treated patients had reversible Grade 3 or 4 hematologic side effects including neutropenia in 67 percent, thrombocytopenia in 61 percent, and anemia in 3 percent of patients. Non-hematologic toxicities were 24% Grade 3 and 5% Grade 4. The Grade 3/4 infection rate was 8%. Zevalin is currently approved in the United States for the treatment of patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL), including patients with rituximab refractory follicular NHL. The Zevalin therapeutic regimen has been given accelerated approval for the treatment of relapsed or refractory, rituximab-naive, low-grade and follicular NHL based on studies using an endpoint of overall response rate, which is a surrogate for progression free survival. About Zevalin(R) Zevalin(R) (Ibritumomab Tiuxetan) is a form of cancer therapy called radioimmunotherapy and is indicated as part of the Zevalin therapeutic regimen for treatment of relapsed or refractory, low-grade or follicular B- cell non-Hodgkin's lymphoma, including patients with rituximab refractory follicular NHL. Zevalin is also indicated, under accelerated approval, for the treatment of relapsed or refractory, rituximab-naive, low- grade and follicular NHL based on studies using a surrogate endpoint of overall response rate. It was approved by the FDA in February of 2002 as the first radioimmunotherapeutic agent for the treatment of NHL. Rare deaths associated with an infusion reaction symptom complex have occurred within 24 hours of rituximab (Rituxan(R)) infusions. Yttrium-90 Zevalin administration results in severe and prolonged cytopenias in most patients. Severe cutaneous and mucocutaneous reactions have been reported. The most serious adverse reactions of the Zevalin therapeutic regimen were primarily hematologic, including neutropenia, thrombocytopenia and anemia. Infusion-related toxicities were associated with pre- administration of rituximab. The risk of hematologic toxicity correlated with the degree of bone marrow involvement prior to Zevalin therapy. Myelodysplasia or acute myelogenous leukemia was observed in 2 percent of patients (8 to 34 months after treatment). Zevalin should only be used by health care professionals qualified by training and experience in the safe use of radionuclides. Patients and healthcare professionals can visit http://www.zevalin.com for more information. About Non-Hodgkin's Lymphoma Non-Hodgkin's lymphoma (NHL) is caused by the abnormal proliferation of white blood cells and normally spreads through the lymphatic system, a system of vessels that drains fluid from the body. NHL can be broadly classified into two main forms -- aggressive NHL, a rapidly spreading acute form of the disease, and indolent NHL, which progresses more slowly. According to the National Cancer Institute's SEER database there were nearly 400,000 people in the U.S. with NHL in 2004. The American Cancer Society estimates that 66,120 people will be diagnosed with NHL in 2008 and more than 19,000 are expected to die. About Cell Therapeutics, Inc. Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit http://www.celltherapeutics.com. This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of Zevalin include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with Zevalin in particular including, without limitation, the potential for Zevalin FIT data to be acceptable to the FDA for this expanded indication or any other indication, the potential that the FDA will not grant priority review to the sBLA determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, and costs of developing, producing and selling Zevalin. There is also a risk that even if label expansion of Zevalin is approved, it may not result in a significant market increase for the drug due to the presence of other treatment options, failure to gain market acceptance and other factors. You should also review the risk factors listed or described from time to time in the Company's filings with the Securities and Exchange Commission including, without limitation, the Company's most recent filings on Forms 10-K, 8-K, and 10-Q. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise. 09 October 2008 - New Characteristics Discovered In Hodgkin Lymphoma the development of new therapy strategies for Hodgkin lymphoma in the future, according to the researchers in Professor Bernd Dörken's laboratory, who collaborated with researchers at the University Tor Vergata, Rome (Italy). It was not until 1994, some 160 years after Hodgkin's lymphoma (HL) was first described by the British physician Thomas Hodgkin (1832), that - using molecular biological methods - scientists discovered that the disease originates from the white blood cells, the B cells. They noticed, however, that the malignant Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) exhibit a phenotype and characteristics that are considerably altered. Although HRS cells are derived from B cells, they have lost the expression of most of the B cell genes due to reprogramming. The research hypothesis of the just-published paper was that the tumor cells, due to the loss of many B-cell specific genes, need alternative signaling pathways to maintain their malignant growth. As Dr. Mathas explained, "Reprogramming can provide the cells of Hodgkin ymphoma with this survival advantage." Hence, the researchers were searching for factors that normally do not originate from B cells. They found what they were looking for in the gene for the cytokine IL-21. Different Functions of IL-21 It has only been a few years since IL-21 was discovered in T cells. The function of IL-21, however, varies greatly depending on the kind of cell. In some cell types IL-21 stimulates the body's protection program, which researchers call programmed cell death or apoptosis. Each cell contains this apoptosis program so that it will self-destruct when it is altered or defective. This prevents the defective cell from damaging the entire organism. Thus, IL-21 stimulates the T cells of the immune system and, for instance, drives cells of the chronic- lymphatic leukemia of the B-cell type (B-CLL) to apoptosis. By contrast, in T-cell leukemias, IL-21 does just the opposite and stimulates malignant growth. For the first time, the researchers from Berlin and Rome were able to show that IL-21 is produced by lymphatic cells originally derived from B cells. IL-21 activates a specific signaling pathway (STAT3), thus up-regulating the expression of a group of specific genes in HRS cells which support the unchecked growth and survival of HRS cells. IL-21 also activates a chemoattractant for cells which suppress the immune system On top of that, according to further findings of the researchers, IL-21 activates a protein (MIP-3 alpha) in the HRS cells that attracts a group of T cells to the tumor which suppress the immune system. In the healthy organism, these regulatory T cells keep the immune system in check and prevent excessive immune responses. In proximity to the HRS cells there are a large number of these regulatory T cells. Attracted by MIP-3- alpha, they can suppress an effective immune defense of the body against the HRS cells. The production of such chemoattractants could, according to the researchers, also be a cause for why Hodgkin lymphoma contains so few tumor cells. They comprise merely 0.1 to one percent of the tissue. Animal experiments have shown that in immunological diseases like rheumatoid arthritis and lupus erythematosus, a disease accompanied by symptoms such as skin changes and inflammation of blood vessels and joints, these symptoms can be significantly improved if IL-21 is inhibited. "If we could block IL- 21 or also MIP-3 alpha in human tumor cells," Dr. Mathas added, "this might be a new therapeutic approach for Hodgkin lymphoma." The present cure rate for the disease - also in its advanced stages - is 80 to 90 percent, particular when chemotherapy is used. However, these therapy regimens might have severe side ffects including the risk of therapy-induced secondary malignancies. ---------------------------- Article adapted by Medical News Today from original press release. ---------------------------- Only recently Dr. Mathas and Dr. Martin Janz were distinguished for their research on Hodgkin ymphoma with the Curt Meyer Memorial Prize of the Berlin Cancer Society. *Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3 alpha Björn Lamprecht1,2, Stephan Kreher1,2, Ioannis Anagnostopoulos4, Korinna Jöhrens4, Giovanni Monteleone3, Franziska Jundt1,2, Harald Stein4, Martin Janz1,2, Bernd Dörken1,2 and Stephan Mathas1,2 1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin;2Hematology, Oncology and Tumorimmunology, Charité, Medical University Berlin, CVK, Augustenburger Platz 1, 13353 Berlin; 3Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy; 4Institute for Pathology, Charité, Medical University Berlin, CBF, Hindenburgdamm 30, 12200 Berlin, Germany; prepublished online August 6, 2008; DOI 10.1182/blood-2008-01-134783 Source: Barbara Bachtler Helmholtz Association of German Research Centres 01 October 2008 - British Lymphology Society Chooses Belfast For Prestigious Annual Conference Tje British Lymphology Society (BLS), the only UK body representing the medical professionals who treat lymphoedema, has chosen Belfast as the venue for its high profile annual conference. Nearly 200 nursing and physiotherapy delegates, plus 11 pharmaceutical companies will be gathering at the Wellington Park Hotel for three days; 5-7 October. Delegates and exhibitors will be exploring and discussing innovative and leading edge developments in the management and treatment of Lymphoedema under the theme: Lymphoedema - Alternative Pathways. In medical terms oedema means swelling. Lymphoedema is swelling resulting from damage to the body's lymph glands. It is a cruel, disabling and disfiguring condition with many complications and side effects. It can occur naturally (the exact cause has not yet been established, even with the power of modern genetic and DNA research); or it can arise from damage to the lymphatic system caused by major surgery - treatment for breast cancer being the prime example. Extensive swelling of limbs can severely limit mobility and make access to treatment very difficult. Many sufferers find it impossible to lead a normal lifestyle. Lymphoedema is also characterised by skin sores and ulceration. There are also problems with diagnosis - many GP's regard swelling and oedema as an obesity, dietary and exercise problem. In fact, as our mothers and grandmothers so perceptively observed, it's a glandular problem - a problem with the lymph glands. British Lymphology Society |