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Lymphland International Lymphedema Online
| 13 March 2010 - A Novel Mechanism Of Drug Delivery - PEGylated Dendrimers - Monash Institute of Pharmaceutical Science (MIPS) researchers, in collaboration with the biotechnology company Starpharma Holdings Ltd (ASX:SPL) have developed a new method to deliver medications that may benefit thousands of patients with particular types of cancer, HIV and lymphatic conditions world-wide. The Melbourne-based research team has shown how PEGylated Polylysine dendrimers, a new type of nano- sized drug delivery system, can be altered to target either the lymphatic system or the bloodstream. Lead researcher at MIPS and the Associate Dean of Research, Professor Chris Porter said the discovery has particular implications for the treatment of diseases which are spread via the lymphatics and lymph nodes. "We are excited by the possibilities that this technology may provide in the improved treatment of particular types of diseases, including metastatic cancer, lymphoma, HIV and metastitial tuberculosis," Professor Porter said. Dendrimers are precisely defined, synthetic nanomaterials that are approximately 5-10 nanometres in diameter. They are made up of layers of polymer surrounding a central core. The dendrimer surface contains many different sites to which drugs may be attached and also attachment sites for materials such as polyethylene glycol (PEG) which can be used to modify the way the dendrimer interacts with the body. PEG can be attached to the dendrimer to 'disguise' it and prevent the body's defence mechanisms from detecting it, thereby slowing the process of breakdown. This allows the delivery system to circulate in the body for an extended time period, maximising the opportunities for the drug to reach the relevant sites. Professor Porter's group and Starpharma have been investigating dendrimer-based drug delivery systems for some time -- but these most recent finding appear to hold particular promise. The data, published in the Journal of Controlled Release, demonstrates that by increasing dendrimer size by increasing the chain length of attached polyethylene glycol chains, a dramatic increase in absorption efficiency after subcutaneous injection can be achieved and transported into the lymphatic system. Conversely, a shorter PEG chain was shown to lead to rapid absorption into the blood. "Our work suggests that careful design of the size and surface characteristics of PEGylated Polylysine dendrimers provides an opportunity to choose whether these delivery systems are absorbed and distributed via the bloodstream or the lymphatic system," Professor Porter said. "The ability to target therapeutic treatments in this way offers the potential to maximise drug concentrations at sites of action within the lymphatic system -- and importantly to minimise concentrations elsewhere, potentially reducing side effects and toxicity. It is still early days, but we're confident the potential for improved patient treatment is significant". Source: Samantha Blair Monash University 02 March 2010 - What Is Lymphedema? What Causes Lymphedema? - Lymphedema, lymphoedema, or lymphatic obstruction is a chronic (long-term) condition in which excess fluid (lymph) collects in tissues causing edema (swelling). Lymphedema can be very debilitating. In short, lymphedema is edema due to lymphatic fluid; a blockage of the lymphatic system. The lymphatic system is an important part of our immune and circulatory systems. Lymphedema commonly affects one of the arms or legs. In some cases, both arms or both legs may be affected. Some patients may experience swelling in the head, genitals or chest. It is often a consequence of surgically removing the lymph nodes in the armpit (axilla) or groin, or their damage caused by radiotherapy. The normal drainage of lymphatic fluid is faulty. Lymphedema can also be caused by a tumor which presses on lymphatic vessels. According to Medilexicon's medical dictionary: Lymphedema is "Swelling (especially in subcutaneous tissues) as a result of obstruction of lymphatic vessels or lymph nodes and the accumulation of large amounts of lymph in the affected region." Lymphedema is incurable. However, with diligent care it can be controlled. What is the lymphatic system? The lymphatic system consists of the tissues and organs that produce and store cells that fight disease and infection. They include the bone marrow, thymus, lymph nodes and spleen, as well as the channels that carry lymph. Most of us know about the circulation system that pumps blood from the heart to the rest of the body. A significant number of individuals, however, are not aware that the body also has a second circulation system - the lymphatic system. There is a series of vessels and glands (lymph nodes) that comprise the lymphatic system. They are spread throughout the body, in a similar way to blood vessels. The lymphatic system has three main functions: •Fighting infection - the lymphatic system transports a watery, clear fluid full of lymphocytes. Lymphocytes are infection-fighting cells. The white fluid is known as lymph. •Draining excess fluid - after blood has circulated through tissues it leaves fluids and proteins behind; these are waste products. The excess fluid is drained through tiny capillaries and into the lymphatic system. After filtering out bacteria, viruses and other undesirable substances or organisms, the clean fluid is then returned to the blood. This filtering is done by the lymphatic system. •Lipid (fat) absorption - the lymphatic system also absorbs lipids from the intestine and transports them to the blood. A disruption to the lymphatic system can eventually undermine its ability to drain fluid properly, resulting in excess fluid (swelling) in parts of the body. Patients with lymphoma have a higher risk of infection complications because their lymphocytes cannot reach parts of the body where swelling occurs. Cellulitis, a type of bacterial skin infection, is a common infection for patients with lymphedema. There are two main types of lymphedema: Primary lymphedema - often called congenital lymphedema. The lymphedema is evident at birth or shortly after puberty. It is caused by a congenital malformation (faulty genes) of the lymphatic system. This type of lymphedema is rare; affecting approximately 1 in every 10,000 people. Secondary lymphedema - the lymphedema occurs as a result of something else, such as an infection, injury, trauma or cancer which affects the lymphatic system. Lymphedema may be a side effect of cancer treatment, such as radiotherapy or the removal of some lymph nodes, which may damage the lymphatic system. This type of lymphedema is more common. According to the National Health Service, UK, approximately 100,000 British people have secondary lymphedema. More women are affected than men. What are the signs and symptoms of lymphedema? A symptom is something the patient feels and reports, while a sign is something other people, such as the doctor detect. For example, pain may be a symptom while a rash may be a sign. Lymphedema signs and symptoms include: •Swelling of either part or the whole leg or arm, may include the fingers or toes. Some patients experience just slight changes in limb size, while others have severe swelling. Some people may find it difficult to wear jewelry, watches or fit into clothes or shoes. •Sometimes the head or neck may swell •The arm or leg feels heavy •The arm or leg feels tight •The range of motion of the limb is restricted (affected limb loses some of its mobility) •Discomfort in the affected limb •The affected limb may ache •There may be a tingling sensation in the affected limb, much like pins and needles •Recurring skin infections in the affected limb •The skin may thicken and harden on the affected limb; blisters or wart-like growths may develop on the skin •Severe fatigue What are the causes of lymphedema? Causes of primary lymphedema - experts say it is caused by mutations in some of the genes that are involved in the development of the lymphatic system. These faulty genes interfere with the lymphatic system's development, undermining its ability to drain fluid properly. A significant number of patients with primary lymphedema have a close relative who has/had the same condition. However, this does not necessarily mean that the offspring of somebody with lymphedema will develop the disorder themselves. Primary lymphedema is more common in females than males. Causes of secondary lymphedema - this type of lymphedema has several possible causes, including: •Cancer surgery - cancer may spread through the body through the lymphatic system. Sometimes surgeons remove lymph nodes to stop the spread. There is a risk the lymphatic system may be affected, leading to lymphedema. Surgery for breast cancer, skin cancer, vulval cancer, cervical cancer, some other female cancers, bladder cancer and penile cancer carry a significant risk of subsequent lymphedema. •Radiation therapy (radiotherapy) - the use of radiation to destroy cancerous tissue can sometimes damage nearby healthy tissue as well. When radiotherapy is used to destroy cancerous cells that are or may be present in the lymph nodes or vessels, there is a risk of node/vessel damage, with subsequent damage to the lymphatic system, resulting in lymphedema. •Infections - severe cellulitis infection, a type of skin infection, may damage tissue around the lymph nodes or vessels. This may lead to scarring, increasing the risk of lymphedema. Some parasite infections which occur in tropical parts of the world can also increase the risk of lymphedema. •Inflammatory conditions - some conditions which cause tissue to swell (become inflamed) may permanently damage the lymphatic system, such as rheumatoid arthritis, dermatitis or eczema. •Cardiovascular diseases - these are diseases that affect blood flow. Some patients with cardiovascular diseases have a higher risk of developing lymphedema, such as those with DVT (deep vein thrombosis), venous leg ulcers and varicose veins (very rare). •Injury and trauma - more rarely, severe skin burns or anything which results in excessive scarring may raise the risk of developing lymphedema. Diagnosing lymphedema Patients who undergo cancer treatment are commonly offered lymphedema assessment as part of their after- care treatment program. When diagnosing lymphedema the doctor may try to rule out other possible causes of swelling, including a blood clot or an infection that does not involve the lymph nodes. If the patient is at risk of lymphedema, e.g. recently had cancer surgery or treatment involving the lymph nodes, the doctor may diagnose lymphedema based on the signs and symptoms. If there isn't an obvious cause for the lymphedema, some imaging tests may be ordered to find out what is causing the swelling, and other signs and symptoms. The following imaging techniques may be used to have a better look at the lymphatic system: •MRI (magnetic resonance imaging) scan - this device uses a magnetic field and radio waves to create detailed 3-D images of the inside of the body. The doctor can get a better look at the limb tissues, and possibly identify characteristics of lymphedema. MRI and some other scans are also useful in ruling out lipedemia; another condition in which the limbs swell due to abnormal fat deposits. •CT (computerized tomography) scan - this device employs tomography. Tomography is the process of generating a two-dimensional image of a slice or section through a 3-dimensional object (a tomogram). The medical device (the machine) is called a CTG scanner; it is a large machine and uses X-rays. This type of scan can reveal areas in the lymphatic system that may be blocked. •Doppler ultrasound scan - this is a variation of the conventional ultrasound. This type of scan may help identify obstructions, if any are present. •Lymphoscintigraphy - a radioactive dye is injected into the lymphatic system. This dye shows up in a special scanner, which can follow the dye's movement through the lymphatic system and identify any blockages. Determining the extent and severity of the swelling: •Water displacement method - the patient places the affected limb in water. The amount of water displaced is measured. The doctor then knows what the volume of the limb is. •Perometery - this is a device that uses infra-red light to measure the volume of the affected body part. •Bioimpedance test - this test can determine how much fluid there is in tissue. Electrodes are placed in different parts of the patient's body. The electrodes release a small electrical charge, which is measured using a hand-held device. The procedure is painless. What are the treatment options for lymphedema? Lymphedema is incurable. However, there is treatment which can help reduce swelling and pain. Complex Decongestive Therapy (CDT) - this is known as the recommended treatment for lymphedema and has four components (listed after the end of this paragraph). It starts with an intensive therapy phase, during which the patient receives daily treatment and training which may be six weeks long. This is followed by the maintenance phase, when the patient is encouraged to take over their own care using techniques that have been taught to them. This will be followed by regular six monthly follow-up meetings. The four CDT components are: •MLD (manual lymphatic drainage) - the lymphedema therapist uses special massage techniques to move fluid into working lymph nodes, where they are drained. It is crucial that this is done by a fully trained lymphedema therapist, and not just a regular masseur. The therapist needs a thorough knowledge of the lymphatic system for this to work. The lymphedema therapist also teaches several massage techniques that can be used during the maintenance phase. Patients who have a history of heart disease, deep vein thrombosis or kidney disease may not be suitable for MLD. •MLLB (multilayer lymphedema bandaging) - muscles surrounding lymph vessels and nodes move the fluid through the lymphatic system. Unlike the circulation of blood there is no central pump (heart). The aim here of bandages and compression garments is to support the muscles and encourage them to move fluid out of the affected body part. MMLB is utilized after MLD to stop fluid from building up again in the limbs. Patients will also be taught how to apply their own bandages and compression garments correctly so that MLLB can continue during the maintenance period. Compression garments may include long sleeves or stockings which compress to encourage the flow of the lymph fluid out of the affected limb. Even when swelling is reduced, the doctor may recommend that the patient continues wearing them to prevent recurrence of swelling. It is important to get garments that fit properly. •Remedial exercises - these are light exercise aimed at encouraging movement of the lymph fluid out of the limb. The exercises involve moving the affected limb. It is important that the exercise not be strenuous or tiring. They should focus on gentle muscle contractions. Each patient is given his/her own personalized exercise plan. This is done with a fully qualified physical therapist (UK: physiotherapist). •Skin care - good skin care reduces the risks of skin infections, such as cellulitis. Patients are taught how to keep their skin clean, and also how to check for cuts, abrasions and signs of infection. Surgery - surgery has historically had disappointing results, compared to non-surgical therapies for lymphedema. However, a new surgical technique using liposuction has proved more successful. It removes fat form the affected limb, resulting in less swelling. Patients have to wear a compression garment for at least one year after the procedure is done. NICE (National Institute for Clinical Excellence), the body that approves therapies for the National Health Service (NHS), UK, says this procedure is acceptable in terms of clinical safety, but adds there is no evidence about its long term effectiveness. What are the possible complications of lymphedema? Skin infections - repeated episodes of cellulitis are common in patients with lymphedema. Cellulitis is a bacterial infection of the dermis - the deep layer of skin - as well as the subcutaneous tissues (fat and soft tissue layer) that are under the skin. Cellulitis is treated with antibiotics. However, if the bacteria manage to get into the bloodstream the patient has a higher risk of developing septicemia (sepsis). Patients who are particularly vulnerable to repeated episodes of cellulitis may be given an emergency supply of antibiotics, to be taken as soon as signs and symptoms appear. Lymphangitis - this is an infection of the lymph vessels, usually caused by Streptococcus, a type of bacteria. If left untreated it can spread to the skin, causing cellulitis, or into the bloodstream, causing septicemia (sepsis). Psychological effects - lymphedema can affect the way the patient looks, which in turn can have a psychological impact, especially among patients who have been coping with the stresses of living with cancer. Some patients with lymphedema have a higher risk of developing depression. Patients who notice signs and symptoms of depression, such as feeling particularly down, or no longer enjoying things in a way they used to, should tell their doctor immediately. Depression can usually be treated effectively. Prevention Looking after your skin - the affected limb is more vulnerable to skin infections as the supply of lymphocytes (which fight infection) is lower than it should be. If the patient takes measures to minimize the risk of cuts and grazes to the skin, his/her risk of subsequent infections may be significantly reduced. The following measures may help: •After cancer treatment avoid heavy activity with that limb; rest it while recovering. •Avoid sun beds, steam rooms and saunas •Do not let the affected area be used for infections or blood pressure readings. If possible, avoid medical procedures on the affected limb •Do not take very hot baths or showers •Do not wear tight fitting clothes •Do not wear tight fitting jewelry •Don't go barefoot outdoors •Keep a watch for changes or breaks in your skin •Keep your skin supple by moisturizing it every day (ask your doctor about this) •Make sure your footwear fits properly •The risk of cuts with an electric razor is much lower •To prevent developing athlete's foot use an anti-fungal foot powder •Use a thimble when you sew •Use gloves when gardening •Use nail clippers to keep your nails short, or see a chiropodist for foot and nail care •When going outside in an area where they may be insects, use insect repellent •When out in the sun use a high factor sun block •When you have a cut, treat it straight away with an antiseptic cream. And keep the area clean •Whenever you can, raise the affected limb above the level of your heart Diet and bodyweight - the heavier a patient with lymphedema is the higher the strain is on the areas that are swollen. A healthy diet, aiming for an ideal body weight, may help alleviate the signs and symptoms of lymphedema. Some patients report that spicy foods make swellings worse. Written by Christian Nordqvist Copyright: Medical News Today Not to be reproduced without permission of Medical News Today 27 February 2010 - FDA Approves Therapy To Treat Gaucher Disease - The U.S. Food and Drug Administration has approved velaglucerase alfa for injection (VPRIV) to treat children and adults with a form of the rare genetic disorder Gaucher disease. Gaucher disease occurs in people who do not produce enough of an enzyme called glucocerebrosidase. Without this enzyme, harmful amounts of a certain fatty substance (lipid) can build up in the liver, spleen, bones, bone marrow and nervous system, and can prevent cells and organs from working properly. About 1 in 50,000 to 1 in 100,000 people in the general population have Gaucher disease. VPRIV provides long-term enzyme replacement therapy for Type 1 Gaucher disease, the most common form of the genetic disorder. It is an alternative to Cerezyme (imiglucerase), another enzyme replacement therapy. Cerezyme is currently in short supply. "The approval of VPRIV will provide a safe and effective alternative treatment for patients with Gaucher disease," said Julie Beitz, M.D., director of the FDA's Office of Drug Evaluation III. "Patients who previously received Cerezyme as an enzyme replacement therapy for their Type 1 Gaucher disease can be safely switched to VPRIV." The safety and effectiveness of VPRIV was assessed in three clinical studies involving 82 patients with Type 1 Gaucher disease ages 4 years and older. The studies included patients who switched to VPRIV after being treated with Cerezyme. The most common adverse reactions to VPRIV are allergic reactions. Other observed adverse reactions with VPRIV are headache, dizziness, abdominal pain, back pain, joint pain, nausea, fatigue/weakness, fever, and prolongation of activated partial thromboplastin time, a measure of clotting time. VPRIV is manufactured by Shire Human Genetic Therapies Inc. of Cambridge, Mass. Source: U.S. Food and Drug Administration 27 February 2010 - Shire Announces FDA Approval Of VPRIV(TM) (velaglucerase Alfa For Injection) For The Treatment Of Type 1 Gaucher Disease - Shire plc (LSE: SHP, Nasdaq: SHPGY), the global specialty biopharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) has granted marketing approval for VPRIV, a human cell line derived enzyme replacement therapy (ERT) for the long-term treatment of Type 1 Gaucher disease in pediatric and adult patients. The FDA designated VPRIV for Priority Review and granted marketing approval in just 6 months. VPRIV offers patients and their physicians a new treatment option at a critical time, as the supply of the previously approved ERT for Gaucher disease is uncertain and remains disrupted. "We have had the opportunity to use VPRIV in clinical trials and actively participated in the expanded access program. We appreciate the support Shire's management team has provided during the last few months to ensure continuity of care for nearly 50 of our patients with Gaucher disease. We are confident the team Shire has put into place will ensure a seamless transition into the post-regulatory period," said Gregory M. Pastores MD, Associate Professor of Neurology and Pediatrics at the NYU School of Medicine in New York. "VPRIV offers patients a therapeutic option that is safe and effective, and our experience with VPRIV has helped build confidence in its use, bolstered by data on low frequency of antibody formation." Shire recognizes that the treatments it develops for life-altering diseases and conditions require specialized service and support offerings. With today's FDA approval of VPRIV, the company has implemented enhancements to its existing OnePath(SM) Access Program with the introduction of a new Co-Pay Assistance Program. The new program was developed based on feedback from the rare disease community. It is designed to simplify the process and paperwork associated with initiation of therapy, and to reduce the financial burden for patients who are treated with Shire HGT therapies in the United States, including VPRIV. The Company has also announced that it will price VPRIV at a 15% savings over the other commercially available ERT for Gaucher disease. New Co-Pay Assistance Program for Eligible U.S. Patients The new co-pay program provides assistance for eligible patients in the U.S. who have commercial prescription insurance, and helps these patients pay for out-of-pocket medication costs for Shire HGT products, regardless of income level. Through this program, Shire HGT intends to cover these patients' insurance co-pay for the first 3 months of their therapy in 2010. In 2011, the Company intends to cap eligible patients' out of pocket prescription expenses at $500. The new Co-Pay Assistance Program will take effect immediately, and will apply to eligible ELAPRASE® (idursulfase) patients and VPRIV™ patients in the U.S. "The last 6 months have been very challenging for the entire Gaucher community, and the approval of VPRIV brings an important new treatment option to patients suffering from Type 1 Gaucher disease," said Rhonda Buyers, CEO / Executive Director, National Gaucher Foundation (NGF). "We at the NGF are excited about this approval, and by the steps that Shire has taken to improve access to treatments for patients with life-altering conditions. This co-pay program will greatly assist the Gaucher patient population, and we appreciate the fact that Shire has taken the time to listen to us and to act on the needs of patients." More about VPRIV The VPRIV application has also been granted accelerated assessment by the European Medicines Agency (EMA) in the European Union (EU). Shire expects to launch VPRIV in the EU by the end of 2010 and in other countries beginning in 2011. Indications and Usage VPRIV™ (velaglucerase alfa for injection) is a hydrolytic lysosomal glucocerebroside-specific enzyme indicated for long-term enzyme replacement therapy for pediatric and adult patients with Type 1 Gaucher disease Dosing and Administration -- 60 Units/kg administered every other week as a 60-minute intravenous infusion. -- Patients currently being treated with imiglucerase for Type 1 Gaucher disease may be switched to VPRIV. Patients previously treated on a stable dose of imiglucerase are recommended to begin treatment with VPRIV at that same dose when they switch from imiglucerase to VPRIV. -- Physicians can make dosage adjustments on an individual patient basis based on achievement and maintenance of therapeutic goals. Clinical trials have evaluated doses ranging from 15 Units/kg to 60 Units/kg every other week. Clinical Trial Results Shire's VPRIV clinical trial program included the largest and most comprehensive set of Phase III trials conducted to date for Gaucher disease. The efficacy of VPRIV was assessed in three clinical studies in a total of 99 patients with type 1 Gaucher disease. Eighty-two patients age 4 years and older received VPRIV and 17 patients age 3 years and older received imiglucerase. Studies I and II were conducted in patients who were not currently receiving Gaucher disease-specific therapy. Study III was conducted in patients who were receiving imiglucerase treatment immediately before starting VPRIV. In these studies, VPRIV was administered intravenously over 60 minutes at doses ranging from 15 Units/kg to 60 Units/kg every other week. Each study met its primary endpoint. Important Safety Information The most serious adverse reactions seen with VPRIV were hypersensitivity reactions. Infusion-related reactions were the most commonly observed adverse reactions in patients treated with VPRIV in clinical studies. The most commonly observed symptoms of infusion-related reactions were: headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia. Generally the infusion- related reactions were mild and, in treatment-naive patients, onset occurred mostly during the first 6 months of treatment and tended to occur less frequently with time. Adverse reactions more commonly seen in pediatric patients compared to those observed in adult patients (>10% difference) include rash, upper respiratory tract infection, prolonged activated partial thromboplastin time, and pyrexia. About Gaucher Disease Gaucher disease is an autosomal recessive disorder caused by mutations in the GBA gene which results in a deficiency of the lysosomal enzyme beta-glucocerebrosidase. This enzymatic deficiency causes an accumulation of glucocerebroside, primarily in macrophages. In this lysosomal storage disorder (LSD), clinical features are reflective of the distribution of Gaucher cells in the liver, spleen, bone marrow, and other organs. The accumulation of glucocerebrosidase in the liver and spleen leads to organomegaly. Presence of Gaucher cells in the bone marrow and spleen lead to clinically significant anemia and thrombocytopenia. Gaucher disease is the most prevalent of the lysosomal storage disorders diseases. Gaucher disease has classically been categorized into 3 clinical types. Type 1 Gaucher disease is characterized by variability in signs, symptoms, severity, and progression. Type 1 is the most common and is distinguished from Type 2 and Type 3 by the lack of early neurological symptoms. SHIRE PLC Shire's strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results. "SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995 Statements included herein that are not historical facts are forward-looking statements. Such forward- looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, the Company's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company's Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate new products for commercialization and/or development; government regulation of the Company's products; the Company's ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company's products; the Company's ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company's ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission. Source: Shire plc 25 February 2010 - Shire Provides Update On Biologics License Application (BLA) Filing For REPLAGAL(R) (agalsidase Alfa) With The U.S. Food And Drug Administration (FDA) - Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, announces it has received Fast Track designation from the FDA for REPLAGAL(R) (agalsidase alfa), its enzyme replacement therapy for Fabry disease. Shire filed a BLA for REPLAGAL in December 2009. The FDA requested additional human pharmacokinetic data to confirm comparability between product that was manufactured in roller bottles, and that which is manufactured in bioreactors. Product made by the bioreactor process is already approved for commercial use in the European Union as well as a number of other countries. As a result of this request, Shire withdrew its December BLA filing, and, at the suggestion of the FDA, requested and received Fast Track designation. Shire will immediately initiate the rolling submission of the REPLAGAL BLA, and will submit the requested pharmacokinetic data around mid-year. Fast Track designation is an FDA-approved process that facilitates the development and expedites the review of drugs to treat serious diseases and fill an unmet medical need with the goal of getting important new treatments to patients earlier. This process allows a company to file the sections of the BLA as they become available instead of filing all the sections at once. It also enables the agency to commence its review and proceed on a rolling basis as the additional sections are completed and submitted for review. "We will continue to work closely with the FDA in the coming months on the rolling BLA submission for REPLAGAL, "said Sylvie Gregoire, President, Shire Human Genetic Therapies. "We remain committed to continuing to provide Fabry patients in the United States with REPLAGAL under the treatment protocol." REPLAGAL is currently approved for the treatment of Fabry disease in 45 countries and has been available to U.S. patients since December 2009 under an FDA-approved treatment protocol filed at the request of FDA. The REPLAGAL early access program was put in place as a result of the supply disruption of the only currently marketed treatment for Fabry disease in the U.S. Financial guidance for 2010 provided in Shire's year-end results press release and earnings call on February 19, 2010 remains unchanged. About REPLAGAL(R) (agalsidase alfa) REPLAGAL is a human form of enzyme alpha-galactosidase A (a-Gal A) manufactured in a human cell line by gene activation. REPLAGAL is approved in 45 countries worldwide. REPLAGAL is not currently approved for commercial sale in the U.S. REPLAGAL is the only human-cell-line-derived form of enzyme replacement therapy (ERT) that is indicated for the long-term treatment of patients with a confirmed diagnosis of Fabry disease ([alpha]- galactosidase A deficiency). About Fabry disease Fabry disease is a lysosomal storage disorder (LSD) that interferes with the body's ability to break down a specific fatty substance ( globotriaosylceramide or Gb3) which accumulates within the body due to deficiency of a specific enzyme ([alpha]-galactosidase A). Fabry disease affects both males and females and can present with a number of signs or symptoms of variable degree, such as cardiovascular and/or renal dysfunction, intense or burning pain, heat intolerance, skin lesions, gastrointestinal complaints, hearing loss, and ocular problems. Lifespan is typically reduced in patients with Fabry disease by approximately 20 years in men and 15 years in women, compared with the general population.1,2 The principal causes of death are renal failure, cardiomyopathy and cerebrovascular events (e.g. stroke).3 Fabry disease affects an estimated 8,000 to 10,000 people worldwide. References 1. MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 2001;38:769-75. 2. MacDermot KD, Holmes A, Miners AH. Natural history of Fabry disease in affected males and obligate carrier females. J Inherit Metab Dis 2001;24 Suppl 2:13-14. 3. Mehta A, Widmer U. Natural history of Fabry disease. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry disease: perspectives from 5 years of FOS. Oxford: Oxford PharmaGenesis Ltd; 2006: p. 183-8. SHIRE PLC Shire's strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results. "SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995 Statements included herein that are not historical facts are forward-looking statements. Such forward- looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, the Company's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company's Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate new products for commercialization and/or development; government regulation of the Company's products; the Company's ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company's products; the Company's ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company's ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission. Source: Shire Pharmaceutical 25 February 2010 - Photoacoustics Technology Could Make Some Lab Processes More Efficient, Says MU Researcher - Knowing the stage of a patient's melanoma is important when choosing the best course of treatment. When the cancer has progressed to the lymph nodes, a more aggressive treatment is needed. Examining an entire lymph node for cancer takes much effort and time; a new technique might help make the process more efficient. University of Missouri researchers in the Christopher S. Bond Life Sciences Center are studying how photoacoustics, or a laser-induced ultrasound, could help scientists locate the general area of the lymph node where melanoma cells could be residing. This new technology could help doctors identify the stage of melanoma with more accuracy. "This method can be used to determine if the cancer has spread from stage 2, where the melanoma is still just in the skin lesion, to stage 3, where the melanoma has spread to the lymph nodes," said John Viator, assistant professor in the Department of Biological Engineering[1] and Department of Dermatology[2]. "If the cancer is still at stage 2, a simple procedure can remove that lesion. If the cancer has progressed from the initial skin lesion into the lymphatic region and possibly the bloodstream, doctors have to make serious decisions about patient care. The cancer may have possibly spread to other organs, such as the liver, lungs or brain." Currently, pathologists must perform several specific and detailed tests to determine if there is cancer in the lymph nodes. This new technology could make the search less time-consuming by identifying a general area of the lymph node that might contain cancer. "It's very similar to identifying a prize inside a cake," Viator said. "Instead of looking through the entire cake, we can use our ultrasound to pinpoint a slice or two that might contain the 'prize.' In the case of the lymph nodes, when you get a signal, this alerts the pathologist that this is an area of the node that might contain cancer cells. At that point, a pathologist would be able to narrow down the search, saving time and money." In the photoacoustic method, a tabletop device scans a lymph node biopsy with laser pulses. About 95 percent of melanoma cells contain melanin, the pigment that gives skin its color, so they react to the laser's beam, absorbing the light. The laser causes the cells to heat and cool rapidly, which makes them expand and contract. This produces a popping noise that special sensors can detect. This method would examine the entire biopsy and identify the general area of the node that has cancer, giving pathologists a better idea of where to look for the cancer. "This method is quicker and simpler and could be used to improve the efficiency of how doctors determine if the cancer has spread from the original skin lesion into the lymphatic system," Viator said. "This technology could be an important tool in our fight against cancer." In the study, Viator took human cancer cells and placed them inside canine lymph nodes. Then, using the laser, he determined the best ways to locate the cancer cells. The next step is to try the procedure using human lymph nodes. The study, "Photoacoustic Detection of Melanoma Micrometastatis in Sentinel Lymph Nodes," was published in the Journal of Biomedical Engineering. Source: Kelsey Jackson University of Missouri-Columbia 19 February 2010 - Lymphedema: Risk Reduction And Management Strategies - There are no scientific studies showing that lymphedema can be prevented, but there are ways to lower your risk of developing this treatment side effect. During the 10th Annual Conference for Young Women Affected by Breast Cancer, we will explore the myths and recent scientific evidence about lymphedema, learn about risk reduction techniques and discuss approaches to lymphedema management, including exercise, physical therapy, lymphatic drainage, massage and other treatment methods. The 10th Annual Conference for Young Women Affected by Breast Cancer is the only international conference dedicated to the critical issues of young breast cancer survivors and those who care about them. Nearly 1,000 young breast cancer survivors, caregivers and medical professionals from around the world are expected to attend the Conference, to be held Friday, Feb. 26-Sunday, Feb. 28 at the Sheraton Atlanta Hotel in Atlanta, Ga. The Lymphedema: Risk Reduction and Management Strategies workshop will take place from 3:30 - 5:00 p. m. on Friday, Feb. 26 , and will be led by physical therapist Jill Binkley, PT, MSc, FAAOMPT, executive director of TurningPoint Women's Healthcare in Alpharetta, Ga. To learn more about the Conference and for a complete list of workshops, visit http://www. youngsurvivorsconference.org. Source Living Beyond Breast Cancer (LBBC) The Young Survival Coalition (YSC) 19 February 2010 - MU Researchers Collaborate To Develop Standard Of Care For Breast Cancer Survivors With Lymphedema - Lymphedema, a chronic swelling condition that can appear after breast cancer surgery, is a risk for 1.3 million breast cancer survivors. Although lymphedema can cause lifelong swelling in the arms, back, neck and chest, there is no national standard of diagnosis or care. Now, University of Missouri researchers are leading the American Lymphedema Framework Project (ALFP), a national, multi-disciplinary collaboration to develop comprehensive guidelines for the assessment, treatment, and management of lymphedema. "We can't cure lymphedema today - we can only manage it," said Jane Armer, MU nursing professor and director of the project at the MU Ellis Fischel Cancer Center. "Lymphedema is a complex, chronic condition. Currently, there are inconsistent approaches to care for lymphedema, and often the most common form of self-management is to not treat it at all." The ALFP, established in 2008, has two main goals: establish a best practices document with evidence- based lymphedema treatment guidelines for health practitioners, and create a minimum data set of all available lymphedema research and clinical data. The ALFP researchers plan to publish the best practices document in 2011. "Part of why there isn't a standard of care is the lack of reliance on current evidence by health practitioners and third party payers, which in turn causes problems with reimbursement from health insurance companies. Many people with lymphedema have to pay out-of-pocket for care," Armer said. "There isn't a clear, national consensus for how to diagnose lymphedema and when to start treating it. The ALFP collaborators aim to document a standard of care reflecting a consensus on best practices that will help solve these problems." Researchers, including those at MU, have found that the most effective method of care for lymphedema is complete decongestive physiotherapy, in which therapists use specialized lymphatic massage techniques to reduce protein-rich fluid buildup. Bandages and compression garments also help to reduce swelling. One of Armer's innovations at MU is measuring patients' arms with a perometer, a machine that was first used to fit garments for swollen limbs. First implemented in a research setting at MU, the machine has a large optoelectric frame that glides over a patient's arm, scans its image and records an estimated limb volume reading. Perometer measurement is as, or more, accurate than several previous methods to measure arm circumference and volume. The machine is now used in about 20 sites across the country. Highlights of MU Sinclair School of Nursing research from the past 10 years reveal that there is a 40 percent higher risk of developing lymphedema in women with a body mass index (BMI) classified as overweight or obese compared to normal-weight women. The researchers also found that younger patients may have less occurrence of the condition but tend to report more symptoms, which could be a result of psychological and aging-related factors. "In addition to our previous findings, we're currently studying whether there are any genetic factors that increase the risk of lymphedema," Armer said. "A pilot study now underway and a proposed multi-site research study will look at the possibility of genetic predisposition for secondary lymphedema. The results could be applied to cancer treatment in which surgery and radiation affect the lymphatic system." In recognition of the leadership in lymphedema research at MU, the ALFP is housed at the MU Ellis Fischel Cancer Center. Armer's research is funded by the National Institutes of Health and is published in several journals, including the Journal of Lymphoedema; Lymphology; Lymphatic Research and Biology; and the Journal of Cancer Survivorship, and presented at conferences throughout the world. The activities of the ALFP have been funded by industry partnerships and grants from the American Cancer Society through The Longaberger Company, a direct-selling company offering home products, and the Longaberger Horizon of Hope Campaign, which provided a grant for breast cancer research and education. Source: Emily Martin University of Missouri-Columbia 12 February 2010 - Shire Presents Positive Efficacy And Safety Data For Velaglucerase Alfa In Treatment Of Naive Patients With Type 1 Gaucher Disease - Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, presented positive results from its first Phase III study (TKT 032) evaluating safety and efficacy of velaglucerase alfa, its investigational enzyme replacement therapy for the treatment of Type 1 Gaucher disease. The data were presented in an oral presentation at the Lysosomal Disease Network (LDN) World Symposium in Miami, Florida. Data from a pediatric subgroup of this study and five year follow-up results from a long-term Phase I/II extension study (TKT025 EXT) conducted in adults were also reported and add to the available data on the long-term safety and efficacy of velaglucerase alfa in patients with Type 1 Gaucher disease. Both studies (TKT032 and TKT025 EXT) met their primary end-points. Additionally, Shire reported important findings from a study that compared patient antibody response to velaglucerase alfa and imiglucerase. All patients enrolled in the velaglucerase alfa Phase III clinical studies underwent a comprehensive panel of tests that were developed and validated to assess antibody response. In each study, samples were first screened using an electrochemiluminescence (ECL) assay. Positive samples were confirmed using a quantitative radioimmunoprecipitation (RIP) assay. Positive cut-points were established for the ECL assay as 5 ng/mL as well as in terms of fixed raw counts, and for the RIP assay as 4 ng/mL. The results suggest significant antigenic differences between velaglucerase alfa and imiglucerase, with only 1% seroconversion rates against velaglucerase alfa. "The combined data presented today provides additional and compelling support for the long-term clinical efficacy and safety of velaglucerase alfa," said Pramod Mistry, MD, PhD, FRCP, Professor of Pediatrics & Internal Medicine at Yale University School of Medicine. "The Gaucher community is very fortunate to have velaglucerase alfa as an option for patients." Results from Study TKT032 in Adults and Children TKT032 was a 12-month, randomized, double-blind, parallel-group global study in 25 treatment-naive patients aged two years and older that evaluated velaglucerase alfa at 45 U/kg and velaglucerase alfa at 60 U/kg. Patients were eligible to participate in the study if they presented with disease-related anemia and had at least one of the following clinical manifestations of Gaucher disease: thrombocytopenia, moderate splenomegaly or a readily palpable enlarged liver. The primary endpoint was change in hemoglobin concentrations from baseline at 60 U/kg. Secondary endpoints for both doses were changes in platelet counts, changes in organ volumes, changes in surrogate markers of Gaucher disease, and for the 45 U/kg dose only, change in hemoglobin concentrations from baseline. At 12 months, in the 60 U/kg group, statistically significant changes in mean hemoglobin concentration increased 23.3%, +2.43 +/- 0.32 g/dL, P<0.0001; mean platelet count increased 65.9%, +50.9 +/- 12.2 x10(9)/L, P=0.0016; and mean spleen volume decreased 50%, -1.92 +/- 0.51% body weight, P=0.0032, from 14.0 multiples of normal [MN] at baseline to 5.75 MN. Mean liver volume decreased 17%, -0.84 +/- 0.33% body weight, P=0.0282, from 1.46 to 1.22 MN. Results for 45 U/kg were consistent with those observed with 60 U/kg; however a dose-related effect in favor of velaglucerase alfa at 60 U/kg was observed by platelet count increase and liver volume reduction between the 2 dose groups. Adverse events reported by at least 20% of all patients included headache, nasopharyngitis, injury, arthralgia, cough, pyrexia, dizziness, influenza, nasal congestion, vomiting, bone pain, and activated partial thromboplastin time (aPTT) prolonged. No drug-related serious adverse events were reported. No patient withdrew from the study due to an adverse event. One patient developed antibodies to velaglucerase alfa. A subpopulation analysis of study TKT032 was conducted to assess the efficacy and safety of velaglucerase alfa among children aged 2-17. Of 25 patients in the trial, 7 pediatric patients (28%) were enrolled and randomized to receive velaglucerase alfa at 60 U/kg (n=4) or 45 U/kg (n=3) as a 1-hour infusion, every other week for 12 months. In this analysis the two dose groups were pooled and results are shown as a percent change from baseline. Following 12 months treatment with with velaglucerase alfa the mean hemoglobin concentration increased 20%, mean platelet counts increased 54%, mean spleen volume, normalized by body weight, decreased 47% (median value 5.0 multiples of normal (MN) decreased from 13.5 MN). Mean liver volume normalized by body weight decreased 13% (median value 1.04 MN decreased from 1.40 MN). Outcomes reported in children were consistent with those seen in the overall population. Due to the small sample sizes, the results did not achieve statistical significance. Most frequently reported adverse events in the pediatric subpopulation were headache, nasopharyngitis, pyrexia, nasal congestion, productive cough, vomiting, and injury. No pediatric participants experienced severe or serious treatment-emergent events. No pediatric patients developed antibodies to velaglucerase alfa. "We are very pleased with the opportunity to present the findings from the first of three Phase III studies for velaglucerase alfa," said Whaijen Soo, MD, PhD, Senior Vice President, Research and Development, Shire Human Genetic Therapies (HGT). "Our program is the largest and most comprehensive set of Phase III clinical trials conducted to date for Gaucher disease, and we look forward to presenting the results from the remaining trials at future scientific meetings." Results from Five-Year Study Ten of 11 adult patients who completed the Phase I/II study of velaglucerase alfa administered at 60 U/kg every other week, enrolled in a long-term extension study. After month-12, all patients were eligible to receive a step-wise dose reduction from 60 U/kg to 45 U/kg (13 weeks) and then to a 30 U/kg maintenance dose upon the achievement of specific therapeutic goals. All patients met therapeutic goals and their dose was subsequently titrated down to the 30 U/kg dose. Seven of 10 patients received home infusions during the extension period. Eight patients (4 male, 4 female) have now received velaglucerase alfa treatment for 60 months. After 5 years, velaglucerase alfa continued to be generally well tolerated and demonstrated substantial and prolonged increases in hemoglobin concentration and platelet count, and substantial and prolonged decreases in liver and spleen volumes in these patients with Type 1 Gaucher disease. At 60 months, the mean increase in hemoglobin concentration from baseline was +2.4 g/dL (95% CI: 1.6, 3.2; 21.3% change) and the mean increase in platelet count from baseline was +85.1 x10(9)/L (95% CI: 59.8,110.4; 157% change). At 57 months, mean percent reduction in normalized liver volume from baseline was 39% (95% CI: -49.1%,-28.5%) and mean percent reduction in normalized spleen volume from baseline was 74% (95% CI: -89.3%,-58.6%). Velaglucerase alfa was found to be generally well tolerated in these 10 patients with no drug-related serious adverse events reported. Treatment-emergent adverse events reported by at least 50% of patients included arthralgia, back pain, pyrexia, upper abdominal pain, pharyngolaryngeal pain and headache. Most adverse events were of mild to moderate severity. No patients withdrew from the trial due to an adverse event. No patients in the 5 year extension study developed antibodies. About velaglucerase alfa Velaglucerase alfa is an investigational enzyme replacement therapy for Type 1 Gaucher disease. Velaglucerase alfa is made using Shire's gene-activation technology, in a human cell line. The enzyme produced has the exact human amino acid sequence and has a human glycosylation pattern. The United States Food and Drug Administration (FDA) has granted Priority Review for the New Drug Application (NDA) for velaglucerase alfa and has issued an action date for the NDA for velaglucerase alfa of February 28, 2010 under the Prescription Drug User Fee Act (PDUFA). About Gaucher disease Gaucher disease is an autosomal recessive disorder caused by mutations in the GBA gene which results in a deficiency of the lysosomal enzyme beta-glucocerebrosidase. This enzymatic deficiency causes an accumulation of glucocerebroside, primarily in macrophages. In this lysosomal storage disorder (LSD), clinical features are reflective of the distribution of Gaucher cells in the liver, spleen, bone marrow, skeleton, and lungs. The accumulation of glucocerebrosidase in the liver and spleen leads to organomegaly. Bone involvement results in skeletal abnormalities and deformities as well as bone pain crises. Deposits in the bone marrow and splenic sequestration lead to clinically significant anemia and thrombocytopenia. Gaucher disease is the most prevalent LSD. Gaucher disease has classically been categorized into 3 clinical types. Type 1 is the most common; it is distinguished from Type 2 and Type 3 by the lack of neurological symptoms. Type 1 Gaucher disease is characterized by variability in signs, symptoms, severity, and progression. SHIRE PLC Shire's strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results. "SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995 Statements included herein that are not historical facts are forward-looking statements. Such forward- looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, the Company's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company's Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate new products for commercialization and/or development; government regulation of the Company's products; the Company's ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company's products; the Company's ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company's ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission. Source: Shire Pharmaceutical 12 February 2010 - Amicus Therapeutics Presents Positive Data Update From Phase 2 Extension Study Of Amigal(TM) For Fabry Disease - Amicus Therapeutics (Nasdaq: FOLD) announced additional positive preliminary data from its ongoing Phase 2 extension study of its investigational drug Amigal™ (migalastat HCl) for Fabry disease at the Lysosomal Disease Network WORLD Symposium in Miami, Florida. The Company also presented encouraging data from preclinical studies evaluating the combination of pharmacological chaperones and enzyme replacement therapy (ERT) for Fabry disease and Pompe disease as well as from preclinical studies examining the use of pharmacological chaperones for the treatment of Parkinson's disease. Phase 2 Extension Study Overview Twenty-six subjects completed either 12 or 24 weeks of treatment with migalastat HCl during the initial Phase 2 studies and twenty-three subjects enrolled in a separate, voluntary long-term extension study designed to evaluate the long-term safety and efficacy of migalastat HCl. Over the course of the initial Phase 2 and extension studies, fifteen subjects have been treated with migalastat HCl for approximately 2-3 years and eight subjects have been treated with migalastat HCl for more than 3 years. Twenty-one subjects continue to receive treatment in the ongoing extension study. Preliminary Data Update from Long-term Phase 2 Extension Study During the course of the extension study, treatment with migalastat HCl has been generally well-tolerated, with no drug-related serious adverse events. The most common adverse events were headache, arthralgia and diarrhea. Renal function is being evaluated by two measures in the extension study, estimated glomerular filtration rate (eGFR) and proteinuria. Preliminary data indicate that eGFR has remained stable out to 2-3 years for all subjects continuing in the extension study and the average annual rate of change in eGFR in subjects identified as responders to migalastat HCl, excluding hyperfiltrators, was +2.0 mL/min/1.73m2. Additionally, trends of reduced proteinuria continued to be observed in subjects identified as responders to migalastat HCl. Derralynn Hughes, MA, DPhil, FRCPath, Senior Lecturer in Haematology Department Academic Haematology, Royal Free & University College Medical School, London, UK, stated, "The additional renal function data with migalastat from the ongoing extension study are encouraging. The eGFR results were particularly of interest as the data at this point in the study compare favorably to the previously published eGFR literature in untreated and ERT-treated Fabry patients." As previously announced, a Phase 3 study intended to support approval in the United States (Study 011) commenced in the second quarter of 2009 and treatment of the first patient began in the fourth quarter of 2009. The Company expects to complete enrollment by the end of 2010 and to have preliminary results in mid-2011. In addition, the Company expects to commence a separate Phase 3 study (Study 012) before year end. Study 012 is intended to support approval in the European Union and will be an 18-month, randomized, open-label study comparing migalastat HCl to ERT in approximately 60 subjects. The primary outcome of efficacy will be renal function as measured by glomerular filtration rate (GFR). John F. Crowley, Chairman and CEO of Amicus Therapeutics, added, "We are very pleased with the continued positive Amigal data and remain confident that our Phase 3 program will be successful. Our focus is the completion of enrollment in Study 011 this year and the commencement of Study 012. We are also very encouraged by the results of our preclinical studies of the chaperone-ERT combination approach as well as the advancements with our Parkinson's program. We look forward to moving these applications of our technology forward in 2010." Preclinical Chaperone-ERT Combination Therapy Data Today Amicus presented data from preclinical studies that evaluated the combination of migalastat HCl and ERT and AT2220 and ERT in mouse models of Fabry and Pompe disease, respectively. Studies of both combinations demonstrated that co-administration of the chaperone with ERT resulted in prolonged half-life of ERT in the circulation, increased enzyme activity in cells and greater substrate reduction in target tissues compared to that seen with ERT alone. Preclinical Parkinson's Disease Data Amicus also presented data from preclinical studies that evaluated the chaperone AT2101 in mouse models of Parkinson's disease. The studies demonstrated that treatment with AT2101 increased the activity of beta- glucocerebrosidase (GCase), prevented accumulation of alpha-synuclein in the brain and improved motor function as assessed in various behavioral tests. The Company also reported that new compounds have been identified that improve on the properties of AT2101 and expand the range of doses and regimens that show motor improvement in mouse models of the disease. About Fabry Disease Fabry disease is a lysosomal storage disorder caused by inherited genetic mutations in the GLA gene, which results in deficient activity of the enzyme alpha-galactosidase A (alpha-Gal A). Deficient alpha-Gal A activity leads to lysosomal accumulation of globotriaosylceramide (GL-3), which is believed to cause the various symptoms of Fabry disease, including pain, kidney failure and increased risk of heart attack and stroke. Migalastat HCl is designed to selectively bind to and stabilize alpha-Gal A, which facilitates proper trafficking of the enzyme to the lysosomes, where it is needed to break down GL-3. Fabry disease is estimated to affect approximately 5,000 to 10,000 people in the developed world, but recent evidence suggests that the disease may be significantly under-diagnosed. The U.S. Food and Drug Administration's Office of Orphan Products Development has granted orphan designation for Amigal in the United States, and the European Commission has designated Amigal as an orphan medicinal product in the European Union. About Pompe Disease Pompe disease affects an estimated 5,000-10,000 individuals world-wide and is clinically heterogeneous in the age of onset, the extent of organ involvement, and the rate of progression. The early onset form of the disease is the most severe, progresses most rapidly, and is characterized by musculoskeletal, pulmonary, gastrointestinal, and cardiac symptoms that usually lead to death from cardio-respiratory failure between 1 and 2 years of age. The late onset form of the disease begins between childhood and adulthood and has a slower rate of progression that is characterized by musculoskeletal and pulmonary symptoms that usually lead to progressive muscle weakness and respiratory insufficiency. A high majority of patients have the late onset form of the disease. The U.S. Food and Drug Administration's Office of Orphan Products Development has granted orphan drug designation for the active ingredient in AT2220 in the United States. About Parkinson's Disease Parkinson's disease (PD) affects more than one million people in the United States alone. Age is the greatest risk factor for development of PD, with a prevalence of about 1% at age 65 that increases with advancing age. Genetic risk factors have also been identified. Recent studies have shown that mutations in the Gba gene for the lysosomal enzyme acid beta-glucocerebrosidase (GCase) are the most common genetic risk factor for PD identified to date. These studies indicate that Parkinson's patients are five-fold more likely than healthy individuals to be Gaucher carriers, meaning that they have one mutant Gba gene on one of their two copies of chromosome 1. About Amicus Therapeutics Amicus Therapeutics is developing orally-administered, small molecule drugs called pharmacological chaperones, a novel, first-in-class approach to treating a broad range of diseases including lysosomal storage disorders and diseases of neurodegeneration. Amicus' lead program is in Phase 3 for the treatment of Fabry disease. Forward Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to preclinical and clinical development of Amicus' candidate drug products, and the timing and reporting of results from preclinical studies and clinical trials evaluating Amicus' candidate drug products. Words such as, but not limited to, "look forward to," "believe," "expect," "anticipate," "estimate," "intend," "plan," "targets," "likely," "will," "would," "should" and "could," and similar expressions or words identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. The inclusion of forward-looking statements should not be regarded as a representation by Amicus that any of its plans will be achieved. Any or all of the forward-looking statements in this press release may turn out to be wrong. They can be affected by inaccurate assumptions Amicus might make or by known or unknown risks and uncertainties. For example, with respect to statements regarding the goals, progress, timing and outcomes of ongoing discussions with regulatory authorities and the potential goals, progress, timing and results of preclinical studies and clinical trials, actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in the business of Amicus, including, without limitation: the potential that results of clinical or pre-clinical studies indicate that the product candidates are unsafe or ineffective; the potential that it may be difficult to enroll patients in our clinical trials; the potential that preclinical and clinical studies could be delayed because we identify serious side effects or other safety issues; the potential that the company will need additional funding to complete all of its studies and, our dependence on third parties in the conduct of our clinical studies. Further, the results of earlier preclinical studies and/or clinical trials may not be predictive of future results. Additionally, all forward looking statements are subject to other risks detailed in our Annual Report on Form 10-K for the year ended December 31, 2008, and our other public filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and Amicus undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995. Source: Amicus Therapeutics 12 February 2010 - Protalix Presents Additional Phase III Data For Taliglucerase Alfa At The WORLD Symposium - Protalix BioTherapeutics, Inc. (NYSE-Amex: PLX), announced that additional data from the Company's pivotal Phase III clinical trial of taliglucerase alfa in patients with Gaucher disease was presented at the Annual Meeting of the Lysosomal Disease Network: WORLD Symposium 2010 in Miami, Florida, during an oral session titled, "Novel Enzyme Replacement Therapy for Gaucher Disease: Phase III Pivotal Clinical Trial with Plant Cell Expressed Recombinant Glucocerebrosidase (prGCD) - taliglucerase alfa." The oral presentation was made by Hanna Rosenbaum M.D., Director of Hematology Day Care Unit, RAMBAM Medical Center, Haifa, Israel, and study investigator. "I believe the data from the Phase III trial demonstrates that taliglucerase alfa is well tolerated and clinically effective in treating Gaucher disease," said Dr. Hanna Rosenbaum. The pivotal Phase III clinical trial was a multi-center, world-wide, randomized, double-blind, parallel group, dose-ranging study to assess the safety and efficacy of taliglucerase alfa in 31 treatment-naive patients suffering from Gaucher disease. In the trial, patients were selected randomly for one of two dosing arms (60 U/kg or 30 U/kg) and received intravenous infusions of taliglucerase alfa once every two weeks for a nine month period. The primary endpoint of the study was a 20% mean reduction from baseline in spleen volume after nine months, as measured by MRI. Major secondary endpoints were an increase in hemoglobin, decrease in liver volume and increase in platelet count. The trial enrolled patients at 11 centers throughout Europe, Israel, North America, South America and South Africa. Taliglucerase alfa significantly reduced mean spleen volume after nine months compared with baseline in both treatment groups. The 60 U/kg group demonstrated a statistically significant mean reduction in spleen volume of 38.0% (p<0.0001) and the 30 U/kg group demonstrated a significant mean reduction in spleen volume of 26.9% (p<0.0001). In addition, the primary endpoint was achieved in both treatment groups after only 6 months of therapy. Statistically significant improvements were also observed for the secondary endpoints after nine months when compared to baseline for the 60 U/kg dose. Patients demonstrated a mean increase in hemoglobin of 2.2 g/dL or 22.2% (p<0.0001), a mean decrease in liver volume of 11.1% (p<0.0001) and a mean elevation in platelet count of 41,494 ml or 72.1% (p=0.0031). For patients in the 30 U/kg dose, statistically significant improvements after nine months compared with baselines were observed for hemoglobin level (increased 1.6 g/dL or 14.8%; p=0.0010) and liver size (decreased 10.48%; p=0.0041); a nominal elevation in platelet count was also seen (11,427 ml or 13.7%; p=0.0460). Thirty patients in the trial had Chitotriosidase measurements, a biomarker for clinical symptoms of Gaucher disease. In these patients, Chitotriosidase decreased from baseline in both the 30U/kg and 60U/kg groups by 47.3% and 58.4% respectively. The safety analysis for both treatment groups showed that taliglucerase alfa was well tolerated and no serious or severe adverse events were reported. Two patients in the trial developed antibodies to taliglucerase alfa and no patients developed neutralizing antibodies. In addition, two patients experienced hypersensitivity reactions to taliglucerase alfa. No anti-taliglucerase antibodies were detected in these patients and both reactions were treated in the physicians' clinic and reversed. Most adverse events were considered unrelated to taliglucerase alfa. The most frequent mild to moderate adverse event was headache. Other mild to moderate adverse events included dizziness, muscle spasm, chest discomfort, nausea, skin irritation and arthalgia. "The Phase III results reported today not only support the use of taliglucerase alfa for the treatment of Gaucher disease, but also support the Company's plant cell based platform technology," said Dr. David Aviezer, President and CEO of Protalix. "Patients who successfully completed this pivotal study have continued to receive taliglucerase alfa as part of our ongoing extension trial, some for over two and a half years." The Company is currently conducting a world-wide switch over study investigating the efficacy and safety of switching to taliglucerase alfa from the currently approved enzyme replacement therapy. In addition, taliglucerase alfa is being provided to patients in the United States under an Expanded Access protocol and to patients in the European Union, Israel and other countries under Named Patient provisions. About Gaucher disease Gaucher disease, an inherited condition, is the most prevalent lysosomal storage disorder, with an incidence of about one in 20,000 live births. People with Gaucher disease do not have enough of an enzyme, beta- glucosidase (glucocerebrosidase) that breaks down a certain type of fat molecule. As a result, lipid engorged cells (called Gaucher cells) amass in different parts of the body, primarily the spleen, liver and bone marrow. Accumulation of Gaucher cells may cause spleen and liver enlargement, anemia, excessive bleeding and bruising, bone disease and a number of other signs and symptoms. About Protalix Protalix is a biopharmaceutical company focused on the development and commercialization of proprietary recombinant therapeutic proteins expressed through its proprietary plant cell based expression system. Protalix's ProCellEx(TM) presents a proprietary method for the expression of recombinant proteins that Protalix believes will allow for the industrial-scale production of recombinant therapeutic proteins in an environment free of mammalian components and viruses. Protalix is also advancing additional recombinant biopharmaceutical drug development programs. Taliglucerase alfa is an enzyme replacement therapy in development under a Special Protocol Assessment with the FDA for Gaucher disease. In August 2009, the FDA granted orphan drug status and fast track designation to taliglucerase alfa for the treatment of Gaucher disease and Protalix filed a rolling NDA submission with the FDA in December 2009. In November 2009, Protalix granted Pfizer Inc. exclusive, worldwide rights to develop and commercialize taliglucerase alfa for the treatment of Gaucher disease, except in Israel. Protalix retained the right to commercialize taliglucerase alfa in Israel. Safe Harbor Statement: To the extent that statements in this press release are not strictly historical, all such statements are forward- looking, and are made pursuant to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk. Factors that might cause material differences include, among others, risks relating to: the successful preclinical development of our product candidates; the completion of clinical trials; the review process of the FDA, the EMEA, other foreign regulatory bodies and other governmental regulatory bodies, including the FDA's and the EMEA's review of any filings we make in connection with the treatment protocol; delays in the FDA's, the EMEA's or other health regulatory authorities' approval of any applications we file or refusals to approve such filings; refusals by such regulatory authorities to approve the marketing and sale of a drug product even after acceptance of an application we file for any such drug product; the identification of lead compounds; the risk that we may fail to satisfy certain conditions relating to grants we have received from the Office of the Chief Scientist of Israel's Ministry of Industry and Trade which may lead to our being required to refund grants previously received together with interest and penalties; the risk that the Office of the Chief Scientist may not deliver to us all of the funds awarded to us; uncertainties related to the ability to attract and retain partners for our technologies and products under development; and other factors described in our filings with the Securities and Exchange Commission. Companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in advanced or late-stage clinical trials, even after obtaining promising earlier trial results or in preliminary findings for such clinical trials. Further, even if favorable testing data is generated by clinical trials of drug products, the FDA, EMEA or any other foreign regulatory authority may not accept or approve an NDA filed by a pharmaceutical or biotechnology company for such drug product. Failure to obtain approval from the FDA, EMEA or any other foreign regulatory authority of any of our drug candidates in a timely manner, if at all, will severely undermine our business and results of operation by reducing our potential marketable products and our ability to generate corresponding product revenues. The statements in this release are valid only as of the date hereof and we disclaim any obligation to update this information. Source: Protalix BioTherapeutics, Inc 11 February 2010 - Raptor Pharmaceutical Corp. To Present Cystinosis Research At Lysosomal Disease Network's 2010 WORLD Symposium - Raptor Pharmaceutical Corp. ("Raptor" or the "Company") (Nasdaq: RPTP), announced the presentation of cystinosis data at the Annual Lysosomal Disease Network WORLD Symposium 2010, being held February 10-12 in Miami, Florida. Biomarker data from a Phase IIb pilot study of Raptor's proprietary delayed- release cysteamine bitartrate ("DR Cysteamine") will be the subject of a poster titled, "Correlation of Plasma Cysteamine and WBC Cystine Levels at Steady State in Patients Treated with Cysteamine Bitartrate." The results will also be published in an upcoming issue of the journal Molecular Genetics and Metabolism. The data supports the effectiveness of pre-dose plasma cysteamine concentration in determining the correct cysteamine dose for nephropathic cystinosis ("cystinosis") patients. Pre-dose plasma cysteamine concentration is an easier biomarker to measure in clinical settings compared to cystine levels in white blood cells ("WBC"s). Researchers in the pilot study found that pre-dose plasma cysteamine concentration has the potential to be a viable alternative to WBC cystine levels as a predictive biomarker for proper cysteamine dosing. Patrice P. Rioux, M.D., Ph.D., Chief Medical Officer said, "We are pleased to share our most recent biomarker findings with the Lysosomal Disease Network, and have taken advantage of this opportunity to further contribute to the study and treatment of cystinosis. Our positive Phase IIb DR Cysteamine clinical trial data demonstrated improved tolerability in cystinosis patients and potential efficacy with less frequent dosing and a lower total daily dosage compared to standard of care, immediate-release cysteamine bitartrate. If we can avoid nocturnal dosing and improve compliance issues associated with today's standard of care, we believe we have the potential to improve both quality of life and overall treatment results for cystinosis patients." Cystinosis is an inborn metabolic error characterized by the abnormal transport of cystine, an amino acid, out of the lysosomes. Failure to treat cystinosis can cause serious health consequences, including renal failure and resultant kidney transplant, growth failure, rickets, photophobia and blindness. Symptom onset typically occurs within the first year of life, when cystine crystals accumulate in various tissues and organs, including the kidneys, brain, liver, thyroid, pancreas, muscles and eyes. Separately, Raptor announced the establishment of a Dutch subsidiary, called Raptor Pharmaceuticals Europe BV, to be used as a base for the Company's European clinical, regulatory, commercial and business development activities. About Raptor Pharmaceutical Corp. Raptor Pharmaceutical Corp. (Nasdaq: RPTP) ("Raptor") is dedicated to speeding the delivery of new treatment options to patients by working to improve existing therapeutics through the application of highly specialized drug targeting platforms and formulation expertise. Raptor focuses on underserved patient populations where it can have the greatest potential impact. Raptor currently has product candidates in clinical development designed to potentially treat nephropathic cystinosis, non-alcoholic steatohepatitis ("NASH"), Huntington's Disease ("HD"), aldehyde dehydrogenase ("ALDH2") deficiency, and a non-opioid solution designed to potentially treat chronic pain. Raptor's preclinical programs are based upon bioengineered novel drug candidates and drug-targeting platforms derived from the human receptor-associated protein ("RAP") and related proteins that are designed to target cancer, neurodegenerative disorders and infectious diseases. FORWARD LOOKING STATEMENTS This document contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements relate to future events or our future results of operation or future financial performance, including, but not limited to the following statements: that Raptor's results will be published in an upcoming issue of Molecular Genetics and Metabolism; that pre-dose plasma cysteamine concentration is effective in determining the correct cysteamine dose for nephropathic cystinosis ("cystinosis") patients and has the potential to be a viable alternative to WBC cystine levels as a predictive biomarker for proper cysteamine dosing; that Raptor's DR Cysteamine has improved tolerability in cystinosis patients and has potential efficacy with less frequent dosing and a lower total daily dosage compared to standard of care, immediate-release cysteamine bitartrate; that Raptor's DR Cysteamine has the potential to improve the quality of life and overall treatment results for cystinosis patients; that Raptor's Dutch subsidiary will be used for the Company's European clinical, regulatory, commercial and business development activities; and Raptor's ability to successfully develop any of its product candidates. These statements are only predictions and involve known and unknown risks, uncertainties and other factors, which may cause the Company's actual results to be materially different from these forward-looking statements. Factors which may significantly change or prevent the Company's forward looking statements from fruition include that Raptor may be unsuccessful in developing any products or acquiring products; that Raptor's technology may not be validated as it progresses further and its methods may not be accepted by the scientific community; that Raptor is unable to retain or attract key employees whose knowledge is essential to the development of its products; that unforeseen scientific difficulties develop with the Company's process; that Raptor's patents are not sufficient to protect essential aspects of its technology; that competitors may invent better technology; that Raptor's products may not work as well as hoped or worse, that the Company's products may harm recipients; and that Raptor may not be able to raise sufficient funds for development or working capital. As well, Raptor's products may never develop into useful products and even if they do, they may not be approved for sale to the public. Raptor cautions readers not to place undue reliance on any such forward-looking statements, which speak only as of the date they were made. Certain of these risks, uncertainties, and other factors are described in greater detail in the Company's filings from time to time with the Securities and Exchange Commission (the "SEC"), which Raptor strongly urges you to read and consider, including the joint proxy statement/prospectus on Form S-4 filed with the SEC on August 19, 2009; Raptor's annual report on Form 8-K filed with the SEC on February 5, 2010; Raptor's quarterly report on Form 10-Q/A filed with the SEC on January 15, 2010, all of which are available free of charge on the SEC's web site at http://www.sec.gov. Subsequent written and oral forward-looking statements attributable to Raptor or to persons acting on its behalf are expressly qualified in their entirety by the cautionary statements set forth in Raptor's reports filed with the SEC. Raptor expressly disclaims any intent or obligation to update any forward-looking statements. Source: Raptor Pharmaceutical Corp ----------------- Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial Objective: To determine the effectiveness of early physiotherapy in reducing the risk of secondary lymphoedema after surgery for breast cancer. Design: Randomised, single blinded, clinical trial. Setting: University hospital in Alcalá de Henares, Madrid, Spain. Participants: 120 women who had breast surgery involving dissection of axillary lymph nodes between May 2005 and June 2007. Intervention: The early physiotherapy group was treated by a physiotherapist with a physiotherapy programme including manual lymph drainage, massage of scar tissue, and progressive active and action assisted shoulder exercises. This group also received an educational strategy. The control group received the educational strategy only. Main outcome measure: Incidence of clinically significant secondary lymphoedema (>2 cm increase in arm circumference measured at two adjacent points compared with the non-affected arm). Results: 116 women completed the one year follow-up. Of these, 18 developed secondary lymphoedema (16%): 14 in the control group (25%) and four in the intervention group (7%). The difference was significant (P=0.01); risk ratio 0.28 (95% confidence interval 0.10 to 0.79). A survival analysis showed a significant difference, with secondary lymphoedema being diagnosed four times earlier in the control group than in the intervention group (intervention/control, hazard ratio 0.26, 95% confidence interval 0.09 to 0.79). Conclusion: Early physiotherapy could be an effective intervention in the prevention of secondary lymphoedema in women for at least one year after surgery for breast cancer involving dissection of axillary lymph nodes. Published 12 January 2010, doi:10.1136/bmj.b5396?Cite this as: BMJ 2010;340:b5396 -- Robert Weiss, MS Lymphedema Patient Advocate National Lymphedema Network ---------------------------- 1. Shire Presents Positive Data For Patients With Type 1 Gaucher Disease Who Switched To VPRIV (TM) - 27 March 2010 Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, presented positive data from a Phase III clinical trial (TKT-034) designed to evaluate the safety of switching to VPRIV (velaglucerase alfa for injection), from imiglucerase, as well as an interim analysis of safety data from an ongoing multicenter open-label treatment protocol (HGT-GCB-058) implemented to provide VPRIV to patients affected by the continuing shortage of imiglucerase. A post-hoc analysis of Phase I/II data on therapeutic goal attainment was also presented at the 2010 American College of Medical Genetics Annual Clinical Genetics Meeting in Albuquerque, New Mexico. These data add to the growing body of clinical evidence which support the use of VPRIV in patients both transitioning from imiglucerase or who are treatment naive. Adult and pediatric patients with Type 1 Gaucher disease were switched from imiglucerase (15-60 U/kg every other week) to the same number of units of VPRIV in the Phase III switch study (40 patients) and the ongoing US treatment protocol (>150 patients). In study TKT-034, no patients developed IgG antibodies to VPRIV, including 3 patients who tested positive for anti-imiglucerase antibodies at screening. In addition, hemoglobin concentration, platelet counts, and liver and spleen volumes remained stable over the course of the one year study, demonstrating safety and maintenance of efficacy over this time frame. One patient in the Phase III trial discontinued due to a serious hypersensitivity reaction and the most common side effects reported in the two studies were infusion-related reactions. "Results from the Phase III study provide important information regarding the safety and sustained efficacy of VPRIV for patients with Type 1 Gaucher disease who were previously on imiglucerase and should help inform treatment decisions during and after the imiglucerase supply shortage," said Dr. Gregory Grabowski, Director of the Division of Human Genetics, Cincinnati Children's Hospital Medical Center and Principal Investigator of the 034 study. "These data confirm what many physicians have experienced." A post hoc analysis from a third study, TKT-025EXT, designed to examine attainment of long-term therapeutic goals in 8 patients with Type 1 Gaucher disease treated with velaglucerase alfa, was also presented at the meeting. The initial dose of 60 U/kg was lowered to 30 U/kg after patients achieved at least 2 of 4 predefined therapeutic goals following 1 year of treatment. Clinically meaningful achievement of long- term therapeutic goals for hemoglobin concentration, platelet counts, and liver and spleen volumes was observed within 4 years of initiation of treatment. Shire also reported important findings that suggested substantial antigenic differences when antibody response to treatment with VPRIV and imiglucerase were compared. Among the 99 patients who enrolled in the Phase III studies the seroconversion rate was 1% (1 of 82) against VPRIV versus 23% (4 of 17) against imiglucerase. Velaglucerase alfa is manufactured in Shire's facility in Cambridge MA, which was inspected and approved by the FDA for the commercial production of VPRIV. Study Results and Design for TKT-034, HGT-GBC-058 and TKT-025EXT TKT-034 In this global, open-label, multicenter study, patients were enrolled in the US (11 sites), Europe (3 sites) and Israel (1 site), and of the 41 patients enrolled, 40 received study drug. One patient discontinued due to a serious hypersensitivity reaction and one patient discontinued at week 31 due to a perceived lack of improvement. At the time of discontinuation, this patient's clinical parameters were stable and consistent with those of the entire group of patients in the study. Hemoglobin concentration, platelet counts, and spleen and liver volume were sustained at therapeutic levels through one year of treatment with VPRIV, as demonstrated by pre-specified efficacy criteria for clinically significant change: -- Hemoglobin concentration: the mean change from baseline was -0.1 g/dL, with a 90 percent confidence interval of -0.3 to 0.1 g/dL, within the predefined efficacy criterion of plus or minus 1 g/dL. -- Platelet counts: the percent change from baseline was +7.0%, with a 90 percent confidence interval of 0.5 to 13.5%, within the predefined efficacy criterion of plus or minus 20%. -- Spleen volume: the percent change from baseline was -5.6%, with a 90 percent confidence interval of -10.8 to -0.4% within the predefined efficacy criterion of plus or minus 15%. -- Liver volume: the percent change from baseline was -0.0%, with a 90 percent confidence interval of -2.6 to 2.6% within the predefined efficacy criterion of plus or minus 15%. Study design The primary objective of TKT-034 was to evaluate the safety of VPRIV in patients with Type 1 Gaucher disease who transitioned from imiglucerase to VPRIV. The secondary objectives were to evaluate changes from baseline in hemoglobin concentration, platelet counts, and spleen and liver volumes by Magnetic Resource Imaging (MRI) after every other week dosing of VPRIV. Ads by Google -------------------------------------------------------------------------------- KAPIDEX (dexlansoprazole) Find Out What Other MD's Know about KAPIDEX www.KAPIDEX.comPatients over the age of two years and receiving imiglucerase at a dose between 15 and 60 U/kg every other week for at least 30 months with no dose change in the last 6 months were eligible, provided they had demonstrated stable hemoglobin concentration and platelet counts. Patients were infused in one hour with the same number of units of VPRIV as their prior imiglucerase dose. HGT-GCB-058 This ongoing multicenter, open-label treatment protocol was initiated at the request of the Food and Drug Administration (FDA) to provide VPRIV to patients who otherwise have limited or no access to imiglucerase due to a continuing supply shortage. Between September 1, 2009 and January 31, 2010, more than 150 patients in the US enrolled into HGT- GCB-058 and received at least one infusion of VPRIV. Of these, 3 were treatment naive and the rest were previously treated with imiglucerase. Following the administration of the first three infusions of VPRIV at the clinical site, patients who experienced no treatment-related serious adverse events or infusion-related adverse events were eligible to transition to home therapy at the discretion of the investigator. Patients were required to return to the clinic site quarterly for observation. An interim safety analysis of the more than 150 patients on the treatment protocol was conducted. Among those patients previously treated with imiglucerase, a total of 18% experienced a treatment emergent adverse event that was possibly or probably related to the study drug. The most commonly observed treatment emergent adverse events among switch patients included at least one infusion-related reaction, nasopharyngitis, nausea, fatigue, headache, dizziness and influenza. Approximately 1% of patients experienced a severe adverse event that was considered to be possibly or probably related to the study drug. TKT-025EXT: Study Results and Design of Therapeutic Goal Analysis This post-hoc analysis of data from the Phase I/II and extension trial of velaglucerase alfa showed that clinically meaningful long-term therapeutic goals were achieved within 4 years of initiation of velaglucerase alfa treatment. The efficacy parameters were evaluated against the therapeutic goals described by Pastores et al (Seminars in Hematology, 2004) aand included absolute and percent changes in hemoglobin levels, platelet counts, and spleen and liver volumes as measured by MRI. Evaluation in this study was limited to those patients who were exposed to velaglucerase alfa for a minimum of 48 months and for whom a complete clinical data set corresponding to the study endoints was available at baseline and annually through 48 months (8 patients, 4 male, 4 female). Patients were evaluated for the achievement of each individual therapeutic goal. The percentage of patients achieving each specific goal over time was determined. In addition the percentage of patients with a complete response (achieved all 4 therapeutic goals) over time was also evaluated. At baseline, no patient was at goal for all 4 clinical parameters: 4 of 8 patients were at goal for hemoglobin concentration, 0 of 8 for platelet count, 4 of 8 for liver volume, and 0 of 8 for spleen volume. After 1 year of treatment, all patients achieved at least 2 therapeutic goals, and all patients maintained clinical parameters for goals that were already at the recommended targets when treatment began. All 8 patients were eligible for and began step-wise dose reduction to velaglucerase alfa 30 U/kg EOW starting between 12 and 18 months. By year 4 of treatment, all patients met goals for all 4 clinical parameters; therefore, 100% achievement was observed for each of the 4 long-term, therapeutic goals. More about VPRIV VPRIV (velaglucerase alfa for injection) was approved by the US FDA as a long-term enzyme replacement therapy for adult and pediatric patients with Type 1 Gaucher disease on February 26, 2010. A marketing application for VPRIV has also been granted accelerated assessment by the European Medicines Agency in the European Union (EU). Shire expects to launch VPRIV in the EU by the end of 2010 and in other countries beginning in 2011. VPRIV is for patients who are treatment naive as well as patients who have been treated with imiglucerase. The most serious adverse reactions seen with VPRIV were hypersensitivity reactions. Infusion-related reactions were the most commonly observed adverse reactions in patients treated with VPRIV in clinical studies. The most commonly observed symptoms of infusion-related reactions were: headache, dizziness, low or high blood pressure, nausea, tiredness and weakness, and fever. Generally the infusion-related reactions were mild and, in treatment-naive patients, onset occurred mostly during the first 6 months of treatment and tended to occur less frequently with time. Adverse reactions more commonly seen in pediatric patients compared to those observed in adult patients (>10% difference) include rash, upper respiratory tract infection, prolonged activated partial thromboplastin time, and fever. As with all therapeutic proteins, there is a potential for immunogenicity. In the clinical studies 1 of 54 treatment-naive patients treated with VPRIV developed IgG class antibodies. It is unknown if the presence of IgG antibodies to VPRIV is associated with a higher risk of infusion reactions. SHIRE PLC Shire's strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results. "SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995 Statements included herein that are not historical facts are forward-looking statements. Such forward- looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, the Company's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company's Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate new products for commercialization and/or development; government regulation of the Company's products; the Company's ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company's products; the Company's ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company's ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission. Source: Shire plc 2. Tumors Hide Out From The Immune System By Mimicking Lymph Nodes - 26 March 2010 A new mechanism explaining how tumors escape the body's natural immune surveillance has recently been discovered at EPFL (Ecole Polytechnique Fédérale de Lausanne) in Switzerland. The study shows how tumors can create a tolerant microenviroment and avoid attack by the immune system by mimicking key features of lymph nodes. The discovery, published in Science and in Science Express, online March 25, 2010, underscores the role of the lymphatic system in cancer and may open up new possibilities for cancer treatment. "The tumor tricks the body into thinking it is healthy tissue," says lead author Melody Swartz, head of the Laboratory of Lymphatic and Cancer Bioengineering (LLCB) and EPFL professor. Swartz and her team set out to understand how immune tolerance is induced by tumors, allowing them to progress and spread. The researchers from EPFL concentrated their efforts on a certain protein that is normally present in healthy lymph nodes to attract T cells and program them to perform vital immune functions. They found that some tumors can secrete this protein to transform the outer layer of the tumor into lymphoid-like tissue. This outer layer then attracts and effectively re-programs the T cells to recognize the tumor as friend not foe, resulting in a tumor that goes undetected by the immune system. Since most tumors progress only if they have escaped the immune system, this new understanding of one mechanism by which the tumor can bypasses or hides from immune defenses is an important step towards future cancer therapies. "The finding that tumors can attract naïve and regulatory T cells and educate them has important implications for tumor immunotherapy," says Jacqui Shields, from LLCB. The study also opens up potential novel areas of research focusing on the relationship between lymphatic systems and cancer research. According to Shields, the concept that tumors mimic lymphoid tissue to alter the host's immune response represents a new understanding of tumors' interactions with the lymphatic system. The laboratory is affiliated with the EPFL's Institute of Bioengineering and the Swiss Institute for Experimental Cancer Research. Source: Ecole Polytechnique Federale de Lausanne (EPFL) ReplyReply AllMove...dadelnimportant emailsoldsentpatientfundssongsGo to Previous message | Go to Next message | Back to Messages Select Message EncodingASCII (ASCII)Greek (ISO-8859-7)Greek (Windows-1253)Latin-10 (ISO-8859-16)Latin-3 (ISO-8859-3)Latin-6 (ISO-8859-10)Latin-7 (ISO- 8859-13)Latin-8 (ISO-8859-14)Latin-9 (ISO-8859-15)W. European (850)W. European (CP858)W. European (HPROMAN8)W. European (MACROMAN8)W. 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Mail Search WelcomeInboxNewFoldersMail Options Copyright © 1994-2010 Yahoo! Inc. All rights reserved. Terms of Service - Copyright/IP Policy - Guidelines NOTICE: We collect personal information on this site. To learn more about how we use your information, see our Privacy Policy - About Our Ads. Addressbook Contacts randy(Nickname) - Randy Ross <lico3_1@yahoo.com> [New Folder]dadelnimportant emailsoldsentpatientfundssongs ------------------------ J1 Open Draft LCD Meeting: California, January 12, 2010 Palmetto GBA J1 A/B MAC will host an Open Draft Local Coverage Determination (LCD) meeting for both Part A and Part B in California, from 9 a.m. to 11 a.m. PST on January 12, 2010. The general public is invited to submit information related to the proposed LCDs for Palmetto GBA's consideration. http://www.palmetto gba.com/palmetto /providers. nsf/vMasterDID/ 7TKQ3P7107? opendocument Applies to: Jurisdiction 1//J1 Part A: General Jurisdiction 1//J1 Part B: General Jurisdiction 1 Part A J1 Open Draft LCD Meeting: California, January 12, 2010 Palmetto GBA J1 A/B MAC will host an Open Draft Local Coverage Determination (LCD) meeting in California, January 12, 2010. The general public is invited to submit information related to the proposed LCDs for Palmetto GBA's consideration. Time: 9 a.m. to 11 a.m. PST, January 12, 2010 Location: Los Angeles Airport Marriott at 5855 West Century Boulevard, Los Angeles, CA 90045 Part B Draft LCDs for Comment Physical Medicine and Rehabilitation Policy (DL28290): Northern California and Southern California To Register for the Meeting on January 12, 2010 Review Draft may be found at: http://www.cms. hhs.gov/mcd/ viewlcd.asp? lcd_id=30698&lcd_version= 6&basket=lcd%3A30698% 3A6%3APhysical+ Medicine+ and+Rehabilitati on+Policy% 3AMAC+%2D+ Part+B%3APalmett o+GBA+%2801192% 29%3A28290 PDF may be found at: http://www.cms. hhs.gov/mcd/ viewlcd_pdf. asp?lcd_id= 30698&lcd_version= 6&contractor_id= 174 Registration will be closed two business days prior to the meeting or once space limitations are reached, whichever comes first. Register now To Present Information at the Meeting Individuals who seek to present information at the meeting should send an e-mail request to J1A. Policy@Palmetto GBA.com or J1B.Policy@Palmetto GBA.com along with a copy of their presentation. Presenters will be selected on a first-come, first-served basis and will be notified as to whether or not they have been selected. If time and space are insufficient to accommodate all who want to speak, Palmetto GBA will accept written comments and give them full and equal consideration. If there are no requests to present information on the draft LCDs, the meeting may be canceled. Please check this page for updates on the meetings. The comment period for this draft LCD will be between 01/07/2010 and 03/01/2010. California Physical Therapists who wish to get their comments in on matters such as billing for bandaging, patient instruction for home self-care, garment measurement and fitting, or other issues should make your concerns known at this meeting. Bob Weiss Fw: Lymphedema bill draft!!!!! legislation item 2 |