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Lymphland International Lymphedema Online
Lymphatic System: Regulator of Lymph Vessel Growth Uncovered - Science Daily (press release) -
Thursday, April 1, 2010
ScienceDaily (Apr. 3, 2010) — In addition to our network of blood vessels, humans have a network
of vessels known as lymphatic vessels. These vessels have a role in many processes in the body,
including regulating fluid levels in tissues and immune surveillance.
Although dysfunction in the lymphatic system contributes to human diseases such as the spread of
cancer to other sites and lymphademas (localized fluid retention and tissue swelling), little is known
about the molecules that regulate the formation of new lymphatic vessels, a process known as
lymphangiogenesis.
However, a team of researchers, led by Sophia Tsai and Ming-Jer Tsai, at Baylor College of Medicine,
Houston, has now identified a role for the gene regulatory protein COUP-TFII in lymphangiogenesis in
mouse embryonic development and tumor lymphangiogenesis in adult mice.
The authors therefore suggest that COUP-TFII might be an effective molecular target in pro-
lymphangiogenic treatment of lymphedemas or in antilymphangiogenic therapy targeting tumor
spreading via the lymphatic vessels.
The research appears in the Journal of Clinical Investigation
---------------------------------------------------
Alt.Health
What the nodes know
Lymphatic drainage unplugs fluid flow and eases acne
By Elizabeth Bromstein
“Ooh, half-price lymphatic drainage massage!” My friend said, checking an email offer from a spa.
“Wow,” I said. Then, “Wait a sec – what exactly does that do?”
“I don’t know. Drains your lymphs?” Sounded about right.
Your lymphatic system is a network of organs, lymph nodes, lymph ducts and lymph vessels that
carries a clear fluid called lymph.
Lymphatic massage, it turns out, is touted for everything from cellulite treatment to post-cancer care
and everything – and I mean everything – in between.
One thing it definitely works for is the treatment of lymphedema, fluid retention and swelling caused by
a compromised lymphatic system. This can be hereditary or (there are many possible causes) the result
of injury to the lymphatic vessels, lymph node dissection, surgery or radiation therapy.
People with lymphedema should be vigilant about where they go for treatment, as I’m told
“certification” can be achieved in a weekend. I’m guessing that if the place also offers facials and
eyebrow threading, you want to check the credentials.
Its other uses are the subject of some discussion.
What the experts say
“Any time we bring nutrients to our cells or clear away their waste, the lymphatic system is involved. It’
s part of our immune response. I work when the system has been disrupted, which can result in
swelling, failure to heal or lack of movement in a joint. I deal with post-cancer patients, especially
breast. The massage is good for injuries or sinus trouble, any kind of congestion in the tissue. The
consumer has to ask the practitioner: ‘How many hours of post-grad training do you have?’ If it’s post-
cancer treatment, the right answer is 135 hours. For a strain, it’s 80.”
JANET McFARLAND, physiotherapist, Toronto
“We have a ‘lymphomaniac facial’ that incorporates massage into a facial. It’s not just for aesthetics,
but for total body health. When you’re prone to water retention and puffiness, that’s an accumulation of
excess lymphatic fluid. We follow the Ayurvedic view that lymphatic stagnation leads to other
accumulation and dysfunction of the body. We also do breast massage. There is a lot of stagnation in
that area because we don’t touch it a lot. The main site of lymph is in the underarm, so we do that, too.”
KRISTEN MA, author, Beauty: Pure + Simple, Toronto
“Lymphatic drainage is effective when the lymphatic system is not responding physiologically. The
studies have not been done on healthy people, but I would suspect that the same intervention will not
increase lymphatic flow beyond what the body requires. The system auto-regulates and is very efficient
when not diseased. Cellulite is not fluid. It’s stored fat. No amount of stimulation is going to change
that. I understand that this treatment is offered in ‘health spas’ for otherwise healthy individuals, but it’s
unlikely that somebody who went through the 180 hours of additional training to get this certification
would use it to treat healthy people.”
STANLEY ROCKSON, Lymphatic Research Foundation advisory board, Stanford, California
“We use the Vodder method of manual lymph drainage (MLD). We lightly manoeuvre the skin to
motivate the fluid to move toward the nearest lymph nodes. Normally, the system does this by itself, but
we help increase the speed of drainage. In a medical setting, the method is used for lymphedema
management, venous congestion, burn patients, ulceration. It’s also used for sprains and strains,
fractures or chronic pain, as with fibromyalgia, migraines, whiplash or tension headaches. It can be
helpful for acne, rosacea, eczema.”
ROBERT HARRIS, director, Dr. Vodder School, Victoria, BC
“Lymphatic drainage is helpful for edema as well as skin issues like scars and acne. When we have
acne, the hair follicles are filled with oil and bacteria. A lymphatic massage decreases pain and swelling.
There are contraindications. These are malignant disease, acute inflammation with infection – because
you can spread that around – and acute allergic reactions. It’s very relaxing, because it’s totally
different from Swedish or deep tissue massage. It’s very gentle.”
THERESA CROLLY, registered massage therapist, Toronto
http://www.nowtoronto.com/lifestyle/story.cfm?content=174399
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A Century-Old Puzzle Comes Together, Scientists ID Potential Protein Trigger In Lung Disease
Sarcoidosis - 04 May 2010
Lung researchers at Johns Hopkins have identified a possible protein trigger responsible for
sarcoidosis, a potentially fatal inflammatory disease marked by tiny clumps of inflammatory cells that
each year leave deep, grainy scars on the lungs, lymph nodes, skin and almost all major organs in
hundreds of thousands of Americans.
The disorder, whose cause has been a persistent mystery for nearly a century, strikes mostly young
adults and disproportionately affects African Americans.
The link between sarcoidosis and overproduction of the suspected protein trigger, called serum amyloid
A, was revealed after a six-year investigation encompassing more than two dozen laboratory
experiments, including some on diseased lung tissue samples from 86 patients in the Baltimore area.
"The increase in production of serum amyloid A explains for the first time how inflammation can persist
in the lungs without being triggered by an active infection," says study senior investigator and
pulmonologist David Moller, M.D., a professor at the Johns Hopkins University School of Medicine.
Moller is also director of the sarcoidosis clinic at The Johns Hopkins Hospital.
Study lead investigator Edward Chen, M.D., says the new findings also clear the path for developing
drug treatments or vaccines that can block serum amyloid A from binding to cell receptors and kicking
off inflammation.
In the short term, however, Moller says his team has plans to use the study results to create diagnostic
tests that could better predict which people with the disease are likely to heal on their own or are more
likely to suffer persistent inflammation, which can lead to scarring, difficulty breathing, and heart failure
that can only be fixed by lung transplantation.
In a report published in February in the American Journal of Respiratory and Critical Care Medicine,
the Johns Hopkins scientists described their research on what was behind the microscopic clusters of
inflamed tissue and white blood cells, or granulomas, which are a defining feature of sarcoidosis.
Such lung lesions are not unique to sarcoidosis and can be triggered by infections, such as in
tuberculosis, which is often confused with sarcoidosis. But unlike tuberculosis, sarcoidosis is not an
infectious disease, does not yield to antibiotics, and is not limited to any particular organ, occurring as
well in the eyes, skin, brain, heart and liver.
Of particular interest to researchers was the role played by so-called amyloids, a set of proteins known
to cause other persistent inflammatory conditions, such as amyloidosis. Indeed, a different kind of
amyloid has been tied to plaques in the brain tissue of people with Alzheimer's disease.
Key among the researchers' findings in sarcoidosis patients was that serum amyloid A stood out
because it was heavily concentrated within the granulomas in diseased and scarred lung tissue.
Researchers found the protein a hundred to a thousand times more widespread in sarcoidosis tissue
samples than in samples from people with tuberculosis, another granuloma-forming lung disease.
Similarly elevated amyloid levels were seen in comparison tests with tissue samples from people with
lung cancer and Crohn's disease.
Further tests in patients' lung cell cultures showed that adding serum amyloid A spiked production of at
least a half-dozen key inflammatory chemicals known to be involved in damaging tissue.
In another series of experiments in mice, the team discovered that granuloma formation in the lungs
sped up when the mice were given injections of synthetic serum amyloid A. Mice had previously been
injected with specially coated plastic beads designed to trigger sarcoidosis-like lesions. Adding the
synthetic protein led to the same biochemical reactions in the mice as observed in humans, suggesting to
the researchers that serum amyloid A played a key role in triggering sarcoidosis.
To better understand how serum amyloid A might be driving granuloma formation, the team used
special antibodies to block various cell surface receptor sites where the protein would bind to the white
blood cells and spur inflammation. Tests in human lung cells showed that blocking one particular
receptor, toll-like receptor-2 (TLR2), inhibited the sustained inflammatory reaction typically associated
with sarcoidosis. But when left to bind on its own, without an antibody blocking TLR2, the open
receptor could attach to serum amyloid A, and raised production of inflammatory chemicals would
ensue.
"Not only have we shown that serum amyloid A is a key protein trigger in sarcoidosis, but we also have
evidence that the resulting inflammation is dependent on binding the protein at toll-like receptor-2,
which opens up a host of possibilities that drugs blocking this binding site could prove an effective
treatment for this disease," says Chen, an assistant professor at Johns Hopkins.
Funding support for the report and research was provided by the National Institutes of Health, the
American Thoracic Society, the Foundation for Sarcoidosis Research, the Life and Breath Foundation,
and the Hospital for the Consumptives of Maryland (Eudowood.)
In addition to Moller and Chen, other Johns Hopkins researchers involved in this study were Zhimin
Song, M.D.; Matthew Willett, B.S.; Shannon Heine, B.S.; Rex Yung, M.D.; Mark Liu, M.D.; Steve
Groshong, M.D., Ph.D.; Ying Zhang, M.D., Ph.D.; and Rubin Tuder, M.D.
Source: Johns Hopkins Medicine
------------
June 25, 2010 - Decongestive Physiotherapy Helps Patients With Painful Leg Swelling –
For patients with painful swelling of the legs caused by chronic venous insufficiency (CVI), a
combination treatment approach called "complete decongestive physiotherapy" improves symptoms,
walking ability, and quality of life, reports a study in Topics in Geriatric Rehabilitation. The journal is
published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of
information and business intelligence for students, professionals, and institutions in medicine, nursing,
allied health, and pharmacy.
Complete (or "complex") decongestive physiotherapy (CDP) can greatly reduce leg swelling and pain
in patients with CVI, according to the new study, led by Yesim Bakar, Ph.D., P.T., of Abant Izzet
Baysal University in Bolu, Turkey. Another paper in the same issue of TGR shows similar benefits of
CDP in a patient with lymphatic obstruction (lymphedema) related to the skin condition psoriasis.
Complete Decongestive Physiotherapy Brings Good Results
Dr Bakar and coauthors evaluated the effects of CDP in 62 older adults (average age 65 years) with
CVI. Patients with CVI have poor blood flow in the veins of the leg, leading to fluid buildup. This
results in painful swelling, making it difficult for patients to walk and perform other activities. Usually
only one leg is affected.
All patients were treated using the CDP approach, which combines four types of physical therapy
treatments:
-- Manual lymph drainage massage to promote drainage of the lymph nodes.
-- Skin care moisturizers and other treatments for skin changes caused by poor circulation.
-- Compression bandages are applied to prevent fluid from reaccumulating.
-- Exercise simple leg exercises to improve blood flow and leg motion.
For the first month, patients met with a physical therapist five days a week for treatment. They also
received education in performing each of the four types of therapy for themselves. The goal was to
keep fluid buildup under control through lifelong, daily self-care.
The CDP treatment program dramatically reduced leg swelling on average, fluid buildup in the affected
leg decreased by the equivalent of nearly half a liter. Pain was also decreased, from an average score of
67 to 18 on a 100-point scale. Patients had improved walking ability, less pain when walking, and
improved ability to perform daily activities. The authors believe that including exercise in the treatment
program was a key factor in improving walking ability.
Dr. Bakar is also a co-author of the other paper, which reports on the use of CDP in a woman with
lymphedema related to the chronic skin condition psoriasis. In patients with lymphedema, obstruction of
the lymph nodes causes similar symptoms of leg pain and swelling. In both the short and long term,
CDP brought significant improvement in pain, swelling, and activity.
Inconclusive Results From Research Into Biologics-Associated Cancer Risk - 18 June 2010
Biologics-naive Juvenile Idiopathic Arthritis (JIA) patients may have an increased risk of cancer
compared with the general Swedish population, according to research presented at EULAR 2010, the
Annual Congress of the European League Against Rheumatism in Rome, Italy. Results of an additional
study, which researched a small cohort of patients showed an increased frequency of cancer in those
receiving the biologic etanercept, however, results were deemed not statistically significant by
researchers.
The results of a population-based Swedish cohort study found that the incidence of cancer among
paediatric patients with JIA identified during the last 40 years was comparable to that seen in the
general population, (0.5 vs. 0.4 cases per 1000 person years, Relative Risk (RR)=1.1, 95%CI 0.9-
1.5). Subset analyses however indicated that subjects diagnosed with JIA since 1987 (the year that the
Swedish patient registry attained nationwide coverage) were at elevated risk of developing cancer
(RR=2.3, 95%CI 1.2-4.4, 13 JIA cancers vs. 30 in comparator), attributed to an increased
occurrence of cancers of the lymphatic system (RR=4.2, 95%CI 1.7-10.7, 8 cancers in JIA vs. 10 in
comparator).
"These results are intriguing and suggest that in the past 20 years, patients with JIA not treated with
biological therapies appear to have an elevated risk of cancer compared with the general population,"
said lead author of the study Dr. Julia Simard, Clinical Epidemiology Unit, Karolinska Institute,
Stockholm, Sweden. "The results of our study indicate that evaluation of cancer risks with biologics in
paediatric populations need to factor in differences in incidence of cancer between these patients and
the general population. From a clinical point of view, it should be remembered that although we noted
an increased risk in relative terms, the excess risks remain low in absolute terms."
The Swedish study assessed a national JIA cohort of 9,020 patients. For each JIA patient, up to five
general-population comparators were identified (n=44,858). In the biologics-naïve JIA cohort, 60
cancers were observed during 131,144 person-years compared to 266 cancers during 661,758
person-years in the population comparator. Researchers noted that sensitivity analyses did not reveal
an explanation for the differences seen between patients identified before and after 1987.
The results of the second study combined data on 1,721 patients treated with etanercept from three
prospective JIA registries in Germany, the UK and the US. Of the 1,641 patients who qualified for the
primary analysis, two cancers were reported. Whilst this yielded a rate higher than expected when
compared to the general population, it was not statistically significant (RR estimated using a
Standardized Incident Ratio (SIR) of 3.7 (0.5-13.4, 95%CI)). This is believed to be in part due to the
low event rate. The interpretation of these findings may be further limited by the fact that the
comparator rates were based on a general population and not a biologics-naïve JIA population, as per
the Swedish study, which suggests this may indicate an increased underlying risk of cancer.
Abstract Numbers: OP0086 & OP0274
Source:
Caroline Butt
European League Against Rheumatism
July 14, 2010 - Protalix BioTherapeutics Receives PDUFA Date For Taliglucerase Alfa -
Protalix BioTherapeutics, Inc. (NYSE-Amex: PLX), announced that the Company's New Drug
Application (NDA) for taliglucerase alfa has been accepted for review by the U.S. Food and Drug
Administration (FDA). The FDA granted taliglucerase alfa a standard review time of ten months,
assigning a Prescription Drug User Fee Act (PDUFA) action date of February 25, 2011. Taliglucerase
alfa is the Company's proprietary plant cell expressed recombinant form of human Glucocerebrosidase
(GCD) which is being developed for the treatment of Gaucher disease under a Special Protocol
Assessment (SPA) with the FDA. Following the completion of a phase III clinical trial of taliglucerase
alfa, the Company completed the submission of a rolling NDA with the FDA in April 2010.
"If approved, taliglucerase alfa will be an attractive and important therapeutic option for Gaucher
patients," said Dr. David Aviezer, President and Chief Executive Officer of Protalix. "We look forward
to working closely with the agency through this final stage of the review process."
Taliglucerase alfa has been granted orphan drug designation from the FDA in the United States. The
Company continues to make taliglucerase alfa available to Gaucher patients in the United States under
an Expanded Access protocol, as well as 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 1 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™ presents a proprietary method for the expression of
recombinant proteins that Protalix believes will allow for the cost-effective, 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. 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.
August 5, 2010 - Ease The Aftermath Of Breast Cancer With New Imaging Technique -
A new study of breast cancer survivors may help physicians ease a common side effect of cancer
treatments. The collaborative research by Eva Sevick, Ph.D., Director of the Center for Molecular
Imaging at the University of Texas Health Science Center in Houston (UTHSC), and Caroline Fife, M.
D., Director of the Memorial Herman Wound Care Clinic at UTHSC, could bring relief to millions.
Their paper appears in the inaugural issue of Biomedical Optics Express, an online, open-access
journal published by the Optical Society (OSA). The papers featured in the journal will encompass
theoretical modeling and simulations, technology development, biomedical studies and clinical
applications.
A substantial number of breast cancer survivors suffer from lymphedema in the aftermath of their cancer
surgeries. In lymphedema, fluids accumulate in the arms, potentially causing disfiguring and debilitating
swelling that can impact quality of life.
Treatments vary, but they generally consist of using manual and pneumatic therapies to "push" or
stimulate the body to remove excess fluid and reduce tissue swelling. Finding out whether a treatment is
working can take months. That's because the current method of assessing progress is to measure the
circumference or volume of a limb and check for changes in swelling - and a size change big enough to
be measured takes time.
During this time, the condition might improve - or it might worsen.
The UTHSC research team has developed what promises to be a more sensitive and more immediate
way to monitor the effectiveness of a treatment. Their new near-infrared fluorescence imaging technique
examines the root cause of lymphedema: blockages or damages in the lymphatic system that prevent
fluid from circulating through the body and cause it to pool in the limbs.
"The lymphatics are like the sewer system of your body," says Sevick. "If they get all plugged up, then
there's a flood."
Nine women - six with lymphedema and three controls - were injected with a near-infrared fluorescent
dye that has been used safely for 50 years at much higher dosages. The dye is taken up by the
lymphatic system. When tissue surfaces are exposed to a dim, near-infrared laser - harmless to the
human body - the dye within fluoresces, revealing its transit through the lymphatic system.
"This is the only method that can directly check for improvements in lymphatic function in one sitting,
before and after a treatment," says Sevick.
Physicians have several treatment options for controlling lymphedema. They may use compression
bandages and massage limbs to manually encourage fluids to drain from the arm. Pneumatic
compression devices, sleeves made of segmented chambers that inflate and squeeze, may provide a
similar benefit at home, but they may not always be covered by Medicare reimbursements because of
lacking direct evidence of their benefit.
"The problem is that there has been no good way to measure direct evidence of benefit," says Sevick.
"Hopefully we can use near-infrared fluorescence imaging technique to show improved lymphatic
function from these treatments."
The NIR fluorescence technique detected statistically significant improvements in fluid flow through the
lymphatic system immediately after the use of pneumatic compression devices. A larger follow-up study
will be needed to confirm the results of this pilot study, says Sevick.
The research was funded by the National Institutes of Health and by Tactile Systems Technology, Inc.,
which manufactures and markets the Flexitouch pneumatic compression devices tested in this research.
The paper:
"Direct evidence of lymphatic function improvement after advanced pneumatic compression device
treatment of lymphedema" by Kristen E. Adams et al.
Source:
Lyndsay Basista
Optical Society of America
August 12, 2010 - HemaQuest Pharmaceuticals Initiates Phase 2 Clinical Trial In EBV-Related
Malignancies -
HemaQuest Pharmaceuticals announced that it has initiated the Company's Phase 2 clinical trial
evaluating its proprietary HQK-1004 therapy for the treatment of lymphomas and related cancers
associated with Epstein-Barr virus (EBV) infection. These EBV-related cancers have poor prognoses
and short patient survival. Currently available cancer therapies are typically much less effective in
patients with EBV-related lymphoid malignancies than in patients who have similar cancers not infected
with the virus.
In a Phase 1 clinical trial previously conducted by HemaQuest's scientific founders, 15 patients with
relapsed or refractory EBV-related lymphomas were treated with a 3-week infusion of our proprietary
therapy, HQK-1004 and the anti-viral drug, Ganciclovir (GCV). Ten patients (67% response rate)
demonstrated objective tumor responses, including several patients with complete tumor responses.
This study provided support for previous laboratory studies demonstrating that HQK 1004 makes
EBV infected cancers susceptible to antiviral therapy.
HQK-1004 acts by inducing the expression of a gene for a viral protein that is the target of several
common anti-viral drugs, including GCV, which eradicate virally infected cells. The gene that makes this
target protein is present in EBV infected tumor cells, but it is not expressed, thus rendering these cells
resistant to anti-viral therapeutics. To overcome this problem, HemaQuest has developed a proprietary
therapeutic approach using HQK-1004, which enables the expression of the viral protein that is the
target of anti-viral drugs. Combining HQK-1004 with anti-viral therapeutics now enables the killing of
viral-infected tumor cells, while uninfected cells should not be affected.
In the current Company-sponsored Phase 2 clinical trial, up to 40 patients with advanced EBV-related
lymphoid malignancies will be treated with HQK-1004 and GCV at several clinical sites in the US and
abroad. The trial will test whether a shorter, 5-day infusion of HQK-1004 can reproduce the promising
results documented in the first clinical trial. With positive clinical results, the Company plans additional
studies to obtain FDA approval for this clinical indication. In addition, HemaQuest intends to test this
therapeutic approach to treat other viral-related cancers.
"This trial represents an important step forward in the development of our HQK-1004 therapy and
builds on the existing clinical safety and efficacy data," commented Susan Perrine, MD, Chief Scientific
Officer and VP of Clinical Affairs at HemaQuest. "Our targeted therapy represents a novel approach to
treating viral-related cancers, which include up to 20% of malignancies. By targeting the virus
associated with the tumor cells, the toxic side effects that commonly occur with traditional
chemotherapy are potentially avoided."
Added Ronald Berenson, MD, President and Chief Executive Officer of HemaQuest, "We are very
pleased to announce the start of this global Phase 2 trial. HQK-1004 has the potential to improve the
outcome of patients with EBV lymphoid malignancies, most of whom have poor responses and limited
survival with current therapies. If this trial is successful, it could lead to a new approach to treating viral-
related cancers, including other hematologic malignancies as well as solid tumors."
Source: HemaQuest Pharmaceuticals
August 24, 2010 - Two-Year Data From Phase 2 Trial Of Genzyme's Eliglustat Tartrate For Gaucher
Disease To Be Published In The Journal Blood -
Genzyme Corporation (NASDAQ: GENZ) announced that the two-year follow-up results from the
phase 2 clinical trial of its investigational therapy known as eliglustat tartrate have been accepted for
publication in the journal Blood. The results have been pre-published on the journal's website and are
available to subscribers.
Eliglustat tartrate, a capsule taken orally, is being developed to provide a convenient treatment
alternative for adult patients with Gaucher disease type 1, and to offer a broader range of treatment
options for patients and physicians to achieve individual therapeutic goals. Current treatments, including
Genzyme's Cerezyme® (imiglucerase for injection), the standard of care for patients with Gaucher
disease type 1, are administered through intravenous infusions.
Genzyme reported last year that the 52-week phase 2 trial of eliglustat tartrate had met its primary
composite endpoint: a clinically meaningful response in at least two of three endpoints (improvements in
spleen size, hemoglobin and platelet levels) in individual patients. The two-year data to be published in
Blood indicate continued improvements across all endpoints. After two years, most patients (85%) had
met at least three of the four hematologic and visceral therapeutic goals established for enzyme
replacement therapy. These data also suggest that eliglustat tartrate may positively impact two
indicators of bone disease, bone mineral density and the presence of dark marrow.
The most common adverse events reported in greater than 10 percent of patients included viral
infections (six patients), urinary tract infections, increased blood pressure, and abdominal pain (three
patients each). Eight drug-related adverse events, including one serious event, were reported in six
patients. All were mild in severity.
These two-year results were presented at the Lysosomal Disease Network WORLD Symposium
earlier this year.
Phase 3 Program
Genzyme is currently enrolling patients in three global, multi-center, phase 3 trials of eliglustat tartrate.
Combined, more than 450 patients are expected to participate, making this the largest clinical program
ever focused on Gaucher disease. Over 50 sites in more than 25 countries are currently participating,
with additional centers planned.
The first phase 3 trial, ENCORE, is a randomized, open-label study for adult patients with Gaucher
disease type 1, designed to compare eliglustat tartrate to Cerezyme. Adult patients who have
previously received enzyme replacement therapy for at least three years and have reached their
therapeutic goals may qualify for this trial. The second trial, ENGAGE, is a randomized, double-blind,
placebo-controlled study for patients with a confirmed diagnosis of Gaucher disease type 1. Patients
who have not received enzyme replacement therapy within 9 months or substrate reduction therapy
within 6 months of participation may qualify for this study. Genzyme recently launched a third trial,
known as EDGE, to compare once-daily dosing of eliglustat tartrate with twice-daily dosing.
Breast Cancer Survivors Don't Need To Be Afraid Of Air Travel: U Of A Study - 21 August 2010
University of Alberta researcher Margie McNeely says results from an international study she was part
of indicates certain precautions about the risk of lymphedema for breast cancer survivors are outdated.
McNeely, from the Faculty of Rehabilitation Medicine, says women who've had breast cancer surgery
are often warned that pressure changes in an airplane cabin could trigger lymphedema, chronic swelling
in the arm. But the study she did with an Australian research team showed that only five per cent of
these women are likely at risk of developing any arm swelling when flying.
The caution about lymphedema risk is for women who have had lymph nodes removed from the
armpit, a common procedure during cancer treatment. McNeely says because these lymph nodes help
drain fluid when they are removed there is the potential for chronic swelling.
McNeely teamed up with Australian researcher Sharon Kilbreath to study the effect of air travel on 60
Canadian breast cancer survivors who were flying to Australia for an International Dragon Boat
Festival. Seventeen of these women were from Edmonton. The study also involved a group of 12
women who were travelling to the festival from different areas of Australia.
The researchers compared both of the participants' arms, the arm where lymph nodes were removed
from the armpit and the opposite unaffected arm, with a device that can detect subtle changes in fluid
difference between the arms. The measurements were done in Canada before they left and again in
Australia when they arrived.
Findings indicate that 95 per cent of the women had no arm swelling. Four women had a slight increase
but at a follow-up test, done six weeks after the women returned to Canada, three were back to
normal and only one woman was found at possible risk for chronic swelling.
McNeely says that, until now, information about air travel and lymphedema risk has not been based on
solid evidence, but says this research shows that while there is a risk of developing lymphedema during
flight, that risk is very low.
McNeely's research was published in the journal Breast Cancer Research and Treatment.
August 27, 2010 - Shire Announces European Approval Of VPRIV(R) (velaglucerase Alfa) For The
Treatment Of Type 1 Gaucher Disease –
Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company,
announced that the European Commission has granted marketing authorisation for VPRIV(R)
(velaglucerase alfa), a human cell line derived enzyme replacement therapy (ERT) for the long-term
treatment of type 1 Gaucher disease. VPRIV has been authorized as an orphan medicine through the
Centralised Procedure, making it available in 30 countries across Europe.
This approval was based on data from Shire's velaglucerase alfa clinical development programme
which represents the largest and most comprehensive clinical data set supporting registration for an
ERT for type 1 Gaucher disease. In total, over 100 Gaucher patients at 24 sites in 10 countries around
the world participated in the clinical studies, all of which met their primary endpoints.
"Gaucher disease is a rare and often debilitating condition," said Professor Tim Cox from the
Department of Medicine, University of Cambridge, and founder of the largest U.K. Gaucher clinic at
Addenbrooke's Hospital. "The European approval of VPRIV is important in that we now have an
alternative, licensed therapeutic enzyme. For type 1 patients the availability of VPRIV provides further
opportunities to individualise treatment options for this complex disorder."
Across Europe, hundreds of type 1 Gaucher patients have been receiving velaglucerase alfa through
early access programmes, developed in partnership with national authorities, Gaucher expert physicians
and patient associations. Globally there are over 850 patients on velaglucerase alfa and demand
continues to be strong. As a result, Shire has implemented a program to carefully monitor demand and
manage requests from physicians and patients in order to ensure long-term, uninterrupted treatment
with VPRIV.
"The Marketing Authorisation for VPRIV in the EU is an important milestone for Shire," said Sylvie
Gregoire, President, Shire Human Genetic Therapies. "Our efforts to accelerate our manufacturing,
clinical and regulatory timelines have resulted in VPRIV's approval in Europe and the US months ahead
of schedule."
Important Safety Information
The most serious adverse reactions in patients treated 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. Other commonly observed
adverse reactions in >10% of patients were: abdominal pain, back pain, joint pain, upper respiratory
tract infection, and activated partial thromboplastin time prolonged. Adverse reactions more commonly
seen in paediatric patients (>10% difference) included upper respiratory tract infection, rash, activated
partial thromboplastin time prolonged, and pyrexia. In clinical trials one patient developed neutralizing
antibodies.
September 1, 2010 - BioMarin Receives Orphan Drug Designation From The FDA For BMN-701
For The Treatment Of Pompe Disease -
BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) announced that it has received orphan drug
designation from the U.S. Food and Drug Administration (FDA) for BMN-701, a novel fusion of
insulin-like growth factor 2 and alpha glucosidase (IGF2-GAA) in development for the treatment of
Pompe disease. An investigational new drug application (IND) for BMN-701 has been submitted,
investigational material has been manufactured and a Phase I/II study is expected to start in the first
quarter of 2011.
"Receiving orphan drug designation from the FDA for BMN-701 is a significant milestone for our
Pompe program. As part of their assessment for designation, the FDA determined that BMN-701 is
sufficiently different from alglusidase alfa (Myozyme/Lumizyme) to allow for a unique orphan
designation. For this reason, clinical superiority over alglusidase alfa will not be necessary to secure
orphan exclusivity for BMN-701," said Jean-Jacques Bienaime, Chief Executive Officer of BioMarin.
"This emphasizes our mission of developing innovative, products for orphan diseases with an unmet
medical need. We believe BMN-701 has the potential to possibly deliver more enzyme to lysosomes
compared to traditional mannose-6-phosphate targeted approaches using the recently acquired GILT
technology."
About Pompe Disease
Pompe disease, a lysosomal storage disorder, is a progressive degenerative disease of the heart
muscle, diaphragm and skeletal muscle. It is caused by a deficiency in the lysosomal enzyme acid alpha
glucosidase which leads to the accumulation of glycogen in myocyte lysosomes and results in cell death.
The incidence is one in 40,000 births. There are two main forms of Pompe disease: adult onset with an
incidence of one in 57,000 births and infantile onset with an incidence of one in 138,000 births. The
current standard of care is Genzyme's Myozyme and Lumizyme. Prognosis with standard of care is
stabilization of the disease or minor improvements for the majority of adult onset patients.
About BioMarin
BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical
conditions. The company's product portfolio comprises four approved products and multiple clinical
and pre-clinical product candidates. Approved products include Naglazyme® (galsulfase) for
mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin;
Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed
through a 50/50 joint venture with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride)
Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck
KGaA of Darmstadt, Germany; and Firdapse™ (amifampridine phosphate), which has been approved
by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS).
Other product candidates include GALNS (N-acetylgalactosamine 6-sulfatase), which is currently in
clinical development for the treatment of MPS IVA and PEG-PAL (PEGylated recombinant
phenylalanine ammonia lyase), which is currently in Phase II clinical development for the treatment of
PKU.
A Century-Old Puzzle Comes Together, Scientists ID Potential Protein Trigger In Lung Disease
Sarcoidosis - 04 May 2010
Lung researchers at Johns Hopkins have identified a possible protein trigger responsible for
sarcoidosis, a potentially fatal inflammatory disease marked by tiny clumps of inflammatory cells that
each year leave deep, grainy scars on the lungs, lymph nodes, skin and almost all major organs in
hundreds of thousands of Americans.
The disorder, whose cause has been a persistent mystery for nearly a century, strikes mostly young
adults and disproportionately affects African Americans.
The link between sarcoidosis and overproduction of the suspected protein trigger, called serum amyloid
A, was revealed after a six-year investigation encompassing more than two dozen laboratory
experiments, including some on diseased lung tissue samples from 86 patients in the Baltimore area.
"The increase in production of serum amyloid A explains for the first time how inflammation can persist
in the lungs without being triggered by an active infection," says study senior investigator and
pulmonologist David Moller, M.D., a professor at the Johns Hopkins University School of Medicine.
Moller is also director of the sarcoidosis clinic at The Johns Hopkins Hospital.
Study lead investigator Edward Chen, M.D., says the new findings also clear the path for developing
drug treatments or vaccines that can block serum amyloid A from binding to cell receptors and kicking
off inflammation.
In the short term, however, Moller says his team has plans to use the study results to create diagnostic
tests that could better predict which people with the disease are likely to heal on their own or are more
likely to suffer persistent inflammation, which can lead to scarring, difficulty breathing, and heart failure
that can only be fixed by lung transplantation.
In a report published in February in the American Journal of Respiratory and Critical Care Medicine,
the Johns Hopkins scientists described their research on what was behind the microscopic clusters of
inflamed tissue and white blood cells, or granulomas, which are a defining feature of sarcoidosis.
Such lung lesions are not unique to sarcoidosis and can be triggered by infections, such as in
tuberculosis, which is often confused with sarcoidosis. But unlike tuberculosis, sarcoidosis is not an
infectious disease, does not yield to antibiotics, and is not limited to any particular organ, occurring as
well in the eyes, skin, brain, heart and liver.
Of particular interest to researchers was the role played by so-called amyloids, a set of proteins known
to cause other persistent inflammatory conditions, such as amyloidosis. Indeed, a different kind of
amyloid has been tied to plaques in the brain tissue of people with Alzheimer's disease.
Key among the researchers' findings in sarcoidosis patients was that serum amyloid A stood out
because it was heavily concentrated within the granulomas in diseased and scarred lung tissue.
Researchers found the protein a hundred to a thousand times more widespread in sarcoidosis tissue
samples than in samples from people with tuberculosis, another granuloma-forming lung disease.
Similarly elevated amyloid levels were seen in comparison tests with tissue samples from people with
lung cancer and Crohn's disease.
Further tests in patients' lung cell cultures showed that adding serum amyloid A spiked production of at
least a half-dozen key inflammatory chemicals known to be involved in damaging tissue.
In another series of experiments in mice, the team discovered that granuloma formation in the lungs
sped up when the mice were given injections of synthetic serum amyloid A. Mice had previously been
injected with specially coated plastic beads designed to trigger sarcoidosis-like lesions. Adding the
synthetic protein led to the same biochemical reactions in the mice as observed in humans, suggesting to
the researchers that serum amyloid A played a key role in triggering sarcoidosis.
To better understand how serum amyloid A might be driving granuloma formation, the team used
special antibodies to block various cell surface receptor sites where the protein would bind to the white
blood cells and spur inflammation. Tests in human lung cells showed that blocking one particular
receptor, toll-like receptor-2 (TLR2), inhibited the sustained inflammatory reaction typically associated
with sarcoidosis. But when left to bind on its own, without an antibody blocking TLR2, the open
receptor could attach to serum amyloid A, and raised production of inflammatory chemicals would
ensue.
"Not only have we shown that serum amyloid A is a key protein trigger in sarcoidosis, but we also have
evidence that the resulting inflammation is dependent on binding the protein at toll-like receptor-2,
which opens up a host of possibilities that drugs blocking this binding site could prove an effective
treatment for this disease," says Chen, an assistant professor at Johns Hopkins.
Funding support for the report and research was provided by the National Institutes of Health, the
American Thoracic Society, the Foundation for Sarcoidosis Research, the Life and Breath Foundation,
and the Hospital for the Consumptives of Maryland (Eudowood.)
In addition to Moller and Chen, other Johns Hopkins researchers involved in this study were Zhimin
Song, M.D.; Matthew Willett, B.S.; Shannon Heine, B.S.; Rex Yung, M.D.; Mark Liu, M.D.; Steve
Groshong, M.D., Ph.D.; Ying Zhang, M.D., Ph.D.; and Rubin Tuder, M.D.
Source: Johns Hopkins Medicine
------------
June 25, 2010 - Decongestive Physiotherapy Helps Patients With Painful Leg Swelling –
For patients with painful swelling of the legs caused by chronic venous insufficiency (CVI), a
combination treatment approach called "complete decongestive physiotherapy" improves symptoms,
walking ability, and quality of life, reports a study in Topics in Geriatric Rehabilitation. The journal is
published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of
information and business intelligence for students, professionals, and institutions in medicine, nursing,
allied health, and pharmacy.
Complete (or "complex") decongestive physiotherapy (CDP) can greatly reduce leg swelling and pain
in patients with CVI, according to the new study, led by Yesim Bakar, Ph.D., P.T., of Abant Izzet
Baysal University in Bolu, Turkey. Another paper in the same issue of TGR shows similar benefits of
CDP in a patient with lymphatic obstruction (lymphedema) related to the skin condition psoriasis.
Complete Decongestive Physiotherapy Brings Good Results
Dr Bakar and coauthors evaluated the effects of CDP in 62 older adults (average age 65 years) with
CVI. Patients with CVI have poor blood flow in the veins of the leg, leading to fluid buildup. This
results in painful swelling, making it difficult for patients to walk and perform other activities. Usually
only one leg is affected.
All patients were treated using the CDP approach, which combines four types of physical therapy
treatments:
-- Manual lymph drainage massage to promote drainage of the lymph nodes.
-- Skin care moisturizers and other treatments for skin changes caused by poor circulation.
-- Compression bandages are applied to prevent fluid from reaccumulating.
-- Exercise simple leg exercises to improve blood flow and leg motion.
For the first month, patients met with a physical therapist five days a week for treatment. They also
received education in performing each of the four types of therapy for themselves. The goal was to
keep fluid buildup under control through lifelong, daily self-care.
The CDP treatment program dramatically reduced leg swelling on average, fluid buildup in the affected
leg decreased by the equivalent of nearly half a liter. Pain was also decreased, from an average score of
67 to 18 on a 100-point scale. Patients had improved walking ability, less pain when walking, and
improved ability to perform daily activities. The authors believe that including exercise in the treatment
program was a key factor in improving walking ability.
Dr. Bakar is also a co-author of the other paper, which reports on the use of CDP in a woman with
lymphedema related to the chronic skin condition psoriasis. In patients with lymphedema, obstruction of
the lymph nodes causes similar symptoms of leg pain and swelling. In both the short and long term,
CDP brought significant improvement in pain, swelling, and activity.
Inconclusive Results From Research Into Biologics-Associated Cancer Risk - 18 June 2010
Biologics-naive Juvenile Idiopathic Arthritis (JIA) patients may have an increased risk of cancer
compared with the general Swedish population, according to research presented at EULAR 2010, the
Annual Congress of the European League Against Rheumatism in Rome, Italy. Results of an additional
study, which researched a small cohort of patients showed an increased frequency of cancer in those
receiving the biologic etanercept, however, results were deemed not statistically significant by
researchers.
The results of a population-based Swedish cohort study found that the incidence of cancer among
paediatric patients with JIA identified during the last 40 years was comparable to that seen in the
general population, (0.5 vs. 0.4 cases per 1000 person years, Relative Risk (RR)=1.1, 95%CI 0.9-
1.5). Subset analyses however indicated that subjects diagnosed with JIA since 1987 (the year that the
Swedish patient registry attained nationwide coverage) were at elevated risk of developing cancer
(RR=2.3, 95%CI 1.2-4.4, 13 JIA cancers vs. 30 in comparator), attributed to an increased
occurrence of cancers of the lymphatic system (RR=4.2, 95%CI 1.7-10.7, 8 cancers in JIA vs. 10 in
comparator).
"These results are intriguing and suggest that in the past 20 years, patients with JIA not treated with
biological therapies appear to have an elevated risk of cancer compared with the general population,"
said lead author of the study Dr. Julia Simard, Clinical Epidemiology Unit, Karolinska Institute,
Stockholm, Sweden. "The results of our study indicate that evaluation of cancer risks with biologics in
paediatric populations need to factor in differences in incidence of cancer between these patients and
the general population. From a clinical point of view, it should be remembered that although we noted
an increased risk in relative terms, the excess risks remain low in absolute terms."
The Swedish study assessed a national JIA cohort of 9,020 patients. For each JIA patient, up to five
general-population comparators were identified (n=44,858). In the biologics-naïve JIA cohort, 60
cancers were observed during 131,144 person-years compared to 266 cancers during 661,758
person-years in the population comparator. Researchers noted that sensitivity analyses did not reveal
an explanation for the differences seen between patients identified before and after 1987.
The results of the second study combined data on 1,721 patients treated with etanercept from three
prospective JIA registries in Germany, the UK and the US. Of the 1,641 patients who qualified for the
primary analysis, two cancers were reported. Whilst this yielded a rate higher than expected when
compared to the general population, it was not statistically significant (RR estimated using a
Standardized Incident Ratio (SIR) of 3.7 (0.5-13.4, 95%CI)). This is believed to be in part due to the
low event rate. The interpretation of these findings may be further limited by the fact that the
comparator rates were based on a general population and not a biologics-naïve JIA population, as per
the Swedish study, which suggests this may indicate an increased underlying risk of cancer.
Abstract Numbers: OP0086 & OP0274
Source:
Caroline Butt
European League Against Rheumatism
July 14, 2010 - Protalix BioTherapeutics Receives PDUFA Date For Taliglucerase Alfa -
Protalix BioTherapeutics, Inc. (NYSE-Amex: PLX), announced that the Company's New Drug
Application (NDA) for taliglucerase alfa has been accepted for review by the U.S. Food and Drug
Administration (FDA). The FDA granted taliglucerase alfa a standard review time of ten months,
assigning a Prescription Drug User Fee Act (PDUFA) action date of February 25, 2011. Taliglucerase
alfa is the Company's proprietary plant cell expressed recombinant form of human Glucocerebrosidase
(GCD) which is being developed for the treatment of Gaucher disease under a Special Protocol
Assessment (SPA) with the FDA. Following the completion of a phase III clinical trial of taliglucerase
alfa, the Company completed the submission of a rolling NDA with the FDA in April 2010.
"If approved, taliglucerase alfa will be an attractive and important therapeutic option for Gaucher
patients," said Dr. David Aviezer, President and Chief Executive Officer of Protalix. "We look forward
to working closely with the agency through this final stage of the review process."
Taliglucerase alfa has been granted orphan drug designation from the FDA in the United States. The
Company continues to make taliglucerase alfa available to Gaucher patients in the United States under
an Expanded Access protocol, as well as 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 1 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™ presents a proprietary method for the expression of
recombinant proteins that Protalix believes will allow for the cost-effective, 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. 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.
August 5, 2010 - Ease The Aftermath Of Breast Cancer With New Imaging Technique -
A new study of breast cancer survivors may help physicians ease a common side effect of cancer
treatments. The collaborative research by Eva Sevick, Ph.D., Director of the Center for Molecular
Imaging at the University of Texas Health Science Center in Houston (UTHSC), and Caroline Fife, M.
D., Director of the Memorial Herman Wound Care Clinic at UTHSC, could bring relief to millions.
Their paper appears in the inaugural issue of Biomedical Optics Express, an online, open-access
journal published by the Optical Society (OSA). The papers featured in the journal will encompass
theoretical modeling and simulations, technology development, biomedical studies and clinical
applications.
A substantial number of breast cancer survivors suffer from lymphedema in the aftermath of their cancer
surgeries. In lymphedema, fluids accumulate in the arms, potentially causing disfiguring and debilitating
swelling that can impact quality of life.
Treatments vary, but they generally consist of using manual and pneumatic therapies to "push" or
stimulate the body to remove excess fluid and reduce tissue swelling. Finding out whether a treatment is
working can take months. That's because the current method of assessing progress is to measure the
circumference or volume of a limb and check for changes in swelling - and a size change big enough to
be measured takes time.
During this time, the condition might improve - or it might worsen.
The UTHSC research team has developed what promises to be a more sensitive and more immediate
way to monitor the effectiveness of a treatment. Their new near-infrared fluorescence imaging technique
examines the root cause of lymphedema: blockages or damages in the lymphatic system that prevent
fluid from circulating through the body and cause it to pool in the limbs.
"The lymphatics are like the sewer system of your body," says Sevick. "If they get all plugged up, then
there's a flood."
Nine women - six with lymphedema and three controls - were injected with a near-infrared fluorescent
dye that has been used safely for 50 years at much higher dosages. The dye is taken up by the
lymphatic system. When tissue surfaces are exposed to a dim, near-infrared laser - harmless to the
human body - the dye within fluoresces, revealing its transit through the lymphatic system.
"This is the only method that can directly check for improvements in lymphatic function in one sitting,
before and after a treatment," says Sevick.
Physicians have several treatment options for controlling lymphedema. They may use compression
bandages and massage limbs to manually encourage fluids to drain from the arm. Pneumatic
compression devices, sleeves made of segmented chambers that inflate and squeeze, may provide a
similar benefit at home, but they may not always be covered by Medicare reimbursements because of
lacking direct evidence of their benefit.
"The problem is that there has been no good way to measure direct evidence of benefit," says Sevick.
"Hopefully we can use near-infrared fluorescence imaging technique to show improved lymphatic
function from these treatments."
The NIR fluorescence technique detected statistically significant improvements in fluid flow through the
lymphatic system immediately after the use of pneumatic compression devices. A larger follow-up study
will be needed to confirm the results of this pilot study, says Sevick.
The research was funded by the National Institutes of Health and by Tactile Systems Technology, Inc.,
which manufactures and markets the Flexitouch pneumatic compression devices tested in this research.
The paper:
"Direct evidence of lymphatic function improvement after advanced pneumatic compression device
treatment of lymphedema" by Kristen E. Adams et al.
Source:
Lyndsay Basista
Optical Society of America
August 12, 2010 - HemaQuest Pharmaceuticals Initiates Phase 2 Clinical Trial In EBV-Related
Malignancies -
HemaQuest Pharmaceuticals announced that it has initiated the Company's Phase 2 clinical trial
evaluating its proprietary HQK-1004 therapy for the treatment of lymphomas and related cancers
associated with Epstein-Barr virus (EBV) infection. These EBV-related cancers have poor prognoses
and short patient survival. Currently available cancer therapies are typically much less effective in
patients with EBV-related lymphoid malignancies than in patients who have similar cancers not infected
with the virus.
In a Phase 1 clinical trial previously conducted by HemaQuest's scientific founders, 15 patients with
relapsed or refractory EBV-related lymphomas were treated with a 3-week infusion of our proprietary
therapy, HQK-1004 and the anti-viral drug, Ganciclovir (GCV). Ten patients (67% response rate)
demonstrated objective tumor responses, including several patients with complete tumor responses.
This study provided support for previous laboratory studies demonstrating that HQK 1004 makes
EBV infected cancers susceptible to antiviral therapy.
HQK-1004 acts by inducing the expression of a gene for a viral protein that is the target of several
common anti-viral drugs, including GCV, which eradicate virally infected cells. The gene that makes this
target protein is present in EBV infected tumor cells, but it is not expressed, thus rendering these cells
resistant to anti-viral therapeutics. To overcome this problem, HemaQuest has developed a proprietary
therapeutic approach using HQK-1004, which enables the expression of the viral protein that is the
target of anti-viral drugs. Combining HQK-1004 with anti-viral therapeutics now enables the killing of
viral-infected tumor cells, while uninfected cells should not be affected.
In the current Company-sponsored Phase 2 clinical trial, up to 40 patients with advanced EBV-related
lymphoid malignancies will be treated with HQK-1004 and GCV at several clinical sites in the US and
abroad. The trial will test whether a shorter, 5-day infusion of HQK-1004 can reproduce the promising
results documented in the first clinical trial. With positive clinical results, the Company plans additional
studies to obtain FDA approval for this clinical indication. In addition, HemaQuest intends to test this
therapeutic approach to treat other viral-related cancers.
"This trial represents an important step forward in the development of our HQK-1004 therapy and
builds on the existing clinical safety and efficacy data," commented Susan Perrine, MD, Chief Scientific
Officer and VP of Clinical Affairs at HemaQuest. "Our targeted therapy represents a novel approach to
treating viral-related cancers, which include up to 20% of malignancies. By targeting the virus
associated with the tumor cells, the toxic side effects that commonly occur with traditional
chemotherapy are potentially avoided."
Added Ronald Berenson, MD, President and Chief Executive Officer of HemaQuest, "We are very
pleased to announce the start of this global Phase 2 trial. HQK-1004 has the potential to improve the
outcome of patients with EBV lymphoid malignancies, most of whom have poor responses and limited
survival with current therapies. If this trial is successful, it could lead to a new approach to treating viral-
related cancers, including other hematologic malignancies as well as solid tumors."
Source: HemaQuest Pharmaceuticals
August 24, 2010 - Two-Year Data From Phase 2 Trial Of Genzyme's Eliglustat Tartrate For Gaucher
Disease To Be Published In The Journal Blood -
Genzyme Corporation (NASDAQ: GENZ) announced that the two-year follow-up results from the
phase 2 clinical trial of its investigational therapy known as eliglustat tartrate have been accepted for
publication in the journal Blood. The results have been pre-published on the journal's website and are
available to subscribers.
Eliglustat tartrate, a capsule taken orally, is being developed to provide a convenient treatment
alternative for adult patients with Gaucher disease type 1, and to offer a broader range of treatment
options for patients and physicians to achieve individual therapeutic goals. Current treatments, including
Genzyme's Cerezyme® (imiglucerase for injection), the standard of care for patients with Gaucher
disease type 1, are administered through intravenous infusions.
Genzyme reported last year that the 52-week phase 2 trial of eliglustat tartrate had met its primary
composite endpoint: a clinically meaningful response in at least two of three endpoints (improvements in
spleen size, hemoglobin and platelet levels) in individual patients. The two-year data to be published in
Blood indicate continued improvements across all endpoints. After two years, most patients (85%) had
met at least three of the four hematologic and visceral therapeutic goals established for enzyme
replacement therapy. These data also suggest that eliglustat tartrate may positively impact two
indicators of bone disease, bone mineral density and the presence of dark marrow.
The most common adverse events reported in greater than 10 percent of patients included viral
infections (six patients), urinary tract infections, increased blood pressure, and abdominal pain (three
patients each). Eight drug-related adverse events, including one serious event, were reported in six
patients. All were mild in severity.
These two-year results were presented at the Lysosomal Disease Network WORLD Symposium
earlier this year.
Phase 3 Program
Genzyme is currently enrolling patients in three global, multi-center, phase 3 trials of eliglustat tartrate.
Combined, more than 450 patients are expected to participate, making this the largest clinical program
ever focused on Gaucher disease. Over 50 sites in more than 25 countries are currently participating,
with additional centers planned.
The first phase 3 trial, ENCORE, is a randomized, open-label study for adult patients with Gaucher
disease type 1, designed to compare eliglustat tartrate to Cerezyme. Adult patients who have
previously received enzyme replacement therapy for at least three years and have reached their
therapeutic goals may qualify for this trial. The second trial, ENGAGE, is a randomized, double-blind,
placebo-controlled study for patients with a confirmed diagnosis of Gaucher disease type 1. Patients
who have not received enzyme replacement therapy within 9 months or substrate reduction therapy
within 6 months of participation may qualify for this study. Genzyme recently launched a third trial,
known as EDGE, to compare once-daily dosing of eliglustat tartrate with twice-daily dosing.
Breast Cancer Survivors Don't Need To Be Afraid Of Air Travel: U Of A Study - 21 August 2010
University of Alberta researcher Margie McNeely says results from an international study she was part
of indicates certain precautions about the risk of lymphedema for breast cancer survivors are outdated.
McNeely, from the Faculty of Rehabilitation Medicine, says women who've had breast cancer surgery
are often warned that pressure changes in an airplane cabin could trigger lymphedema, chronic swelling
in the arm. But the study she did with an Australian research team showed that only five per cent of
these women are likely at risk of developing any arm swelling when flying.
The caution about lymphedema risk is for women who have had lymph nodes removed from the
armpit, a common procedure during cancer treatment. McNeely says because these lymph nodes help
drain fluid when they are removed there is the potential for chronic swelling.
McNeely teamed up with Australian researcher Sharon Kilbreath to study the effect of air travel on 60
Canadian breast cancer survivors who were flying to Australia for an International Dragon Boat
Festival. Seventeen of these women were from Edmonton. The study also involved a group of 12
women who were travelling to the festival from different areas of Australia.
The researchers compared both of the participants' arms, the arm where lymph nodes were removed
from the armpit and the opposite unaffected arm, with a device that can detect subtle changes in fluid
difference between the arms. The measurements were done in Canada before they left and again in
Australia when they arrived.
Findings indicate that 95 per cent of the women had no arm swelling. Four women had a slight increase
but at a follow-up test, done six weeks after the women returned to Canada, three were back to
normal and only one woman was found at possible risk for chronic swelling.
McNeely says that, until now, information about air travel and lymphedema risk has not been based on
solid evidence, but says this research shows that while there is a risk of developing lymphedema during
flight, that risk is very low.
McNeely's research was published in the journal Breast Cancer Research and Treatment.
August 27, 2010 - Shire Announces European Approval Of VPRIV(R) (velaglucerase Alfa) For The
Treatment Of Type 1 Gaucher Disease –
Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company,
announced that the European Commission has granted marketing authorisation for VPRIV(R)
(velaglucerase alfa), a human cell line derived enzyme replacement therapy (ERT) for the long-term
treatment of type 1 Gaucher disease. VPRIV has been authorized as an orphan medicine through the
Centralised Procedure, making it available in 30 countries across Europe.
This approval was based on data from Shire's velaglucerase alfa clinical development programme
which represents the largest and most comprehensive clinical data set supporting registration for an
ERT for type 1 Gaucher disease. In total, over 100 Gaucher patients at 24 sites in 10 countries around
the world participated in the clinical studies, all of which met their primary endpoints.
"Gaucher disease is a rare and often debilitating condition," said Professor Tim Cox from the
Department of Medicine, University of Cambridge, and founder of the largest U.K. Gaucher clinic at
Addenbrooke's Hospital. "The European approval of VPRIV is important in that we now have an
alternative, licensed therapeutic enzyme. For type 1 patients the availability of VPRIV provides further
opportunities to individualise treatment options for this complex disorder."
Across Europe, hundreds of type 1 Gaucher patients have been receiving velaglucerase alfa through
early access programmes, developed in partnership with national authorities, Gaucher expert physicians
and patient associations. Globally there are over 850 patients on velaglucerase alfa and demand
continues to be strong. As a result, Shire has implemented a program to carefully monitor demand and
manage requests from physicians and patients in order to ensure long-term, uninterrupted treatment
with VPRIV.
"The Marketing Authorisation for VPRIV in the EU is an important milestone for Shire," said Sylvie
Gregoire, President, Shire Human Genetic Therapies. "Our efforts to accelerate our manufacturing,
clinical and regulatory timelines have resulted in VPRIV's approval in Europe and the US months ahead
of schedule."
Important Safety Information
The most serious adverse reactions in patients treated 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. Other commonly observed
adverse reactions in >10% of patients were: abdominal pain, back pain, joint pain, upper respiratory
tract infection, and activated partial thromboplastin time prolonged. Adverse reactions more commonly
seen in paediatric patients (>10% difference) included upper respiratory tract infection, rash, activated
partial thromboplastin time prolonged, and pyrexia. In clinical trials one patient developed neutralizing
antibodies.
September 1, 2010 - BioMarin Receives Orphan Drug Designation From The FDA For BMN-701
For The Treatment Of Pompe Disease -
BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) announced that it has received orphan drug
designation from the U.S. Food and Drug Administration (FDA) for BMN-701, a novel fusion of
insulin-like growth factor 2 and alpha glucosidase (IGF2-GAA) in development for the treatment of
Pompe disease. An investigational new drug application (IND) for BMN-701 has been submitted,
investigational material has been manufactured and a Phase I/II study is expected to start in the first
quarter of 2011.
"Receiving orphan drug designation from the FDA for BMN-701 is a significant milestone for our
Pompe program. As part of their assessment for designation, the FDA determined that BMN-701 is
sufficiently different from alglusidase alfa (Myozyme/Lumizyme) to allow for a unique orphan
designation. For this reason, clinical superiority over alglusidase alfa will not be necessary to secure
orphan exclusivity for BMN-701," said Jean-Jacques Bienaime, Chief Executive Officer of BioMarin.
"This emphasizes our mission of developing innovative, products for orphan diseases with an unmet
medical need. We believe BMN-701 has the potential to possibly deliver more enzyme to lysosomes
compared to traditional mannose-6-phosphate targeted approaches using the recently acquired GILT
technology."
About Pompe Disease
Pompe disease, a lysosomal storage disorder, is a progressive degenerative disease of the heart
muscle, diaphragm and skeletal muscle. It is caused by a deficiency in the lysosomal enzyme acid alpha
glucosidase which leads to the accumulation of glycogen in myocyte lysosomes and results in cell death.
The incidence is one in 40,000 births. There are two main forms of Pompe disease: adult onset with an
incidence of one in 57,000 births and infantile onset with an incidence of one in 138,000 births. The
current standard of care is Genzyme's Myozyme and Lumizyme. Prognosis with standard of care is
stabilization of the disease or minor improvements for the majority of adult onset patients.
About BioMarin
BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical
conditions. The company's product portfolio comprises four approved products and multiple clinical
and pre-clinical product candidates. Approved products include Naglazyme® (galsulfase) for
mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin;
Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed
through a 50/50 joint venture with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride)
Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck
KGaA of Darmstadt, Germany; and Firdapse™ (amifampridine phosphate), which has been approved
by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS).
Other product candidates include GALNS (N-acetylgalactosamine 6-sulfatase), which is currently in
clinical development for the treatment of MPS IVA and PEG-PAL (PEGylated recombinant
phenylalanine ammonia lyase), which is currently in Phase II clinical development for the treatment of
PKU.
Thursday, April 1, 2010
ScienceDaily (Apr. 3, 2010) — In addition to our network of blood vessels, humans have a network
of vessels known as lymphatic vessels. These vessels have a role in many processes in the body,
including regulating fluid levels in tissues and immune surveillance.
Although dysfunction in the lymphatic system contributes to human diseases such as the spread of
cancer to other sites and lymphademas (localized fluid retention and tissue swelling), little is known
about the molecules that regulate the formation of new lymphatic vessels, a process known as
lymphangiogenesis.
However, a team of researchers, led by Sophia Tsai and Ming-Jer Tsai, at Baylor College of Medicine,
Houston, has now identified a role for the gene regulatory protein COUP-TFII in lymphangiogenesis in
mouse embryonic development and tumor lymphangiogenesis in adult mice.
The authors therefore suggest that COUP-TFII might be an effective molecular target in pro-
lymphangiogenic treatment of lymphedemas or in antilymphangiogenic therapy targeting tumor
spreading via the lymphatic vessels.
The research appears in the Journal of Clinical Investigation
---------------------------------------------------
Alt.Health
What the nodes know
Lymphatic drainage unplugs fluid flow and eases acne
By Elizabeth Bromstein
“Ooh, half-price lymphatic drainage massage!” My friend said, checking an email offer from a spa.
“Wow,” I said. Then, “Wait a sec – what exactly does that do?”
“I don’t know. Drains your lymphs?” Sounded about right.
Your lymphatic system is a network of organs, lymph nodes, lymph ducts and lymph vessels that
carries a clear fluid called lymph.
Lymphatic massage, it turns out, is touted for everything from cellulite treatment to post-cancer care
and everything – and I mean everything – in between.
One thing it definitely works for is the treatment of lymphedema, fluid retention and swelling caused by
a compromised lymphatic system. This can be hereditary or (there are many possible causes) the result
of injury to the lymphatic vessels, lymph node dissection, surgery or radiation therapy.
People with lymphedema should be vigilant about where they go for treatment, as I’m told
“certification” can be achieved in a weekend. I’m guessing that if the place also offers facials and
eyebrow threading, you want to check the credentials.
Its other uses are the subject of some discussion.
What the experts say
“Any time we bring nutrients to our cells or clear away their waste, the lymphatic system is involved. It’
s part of our immune response. I work when the system has been disrupted, which can result in
swelling, failure to heal or lack of movement in a joint. I deal with post-cancer patients, especially
breast. The massage is good for injuries or sinus trouble, any kind of congestion in the tissue. The
consumer has to ask the practitioner: ‘How many hours of post-grad training do you have?’ If it’s post-
cancer treatment, the right answer is 135 hours. For a strain, it’s 80.”
JANET McFARLAND, physiotherapist, Toronto
“We have a ‘lymphomaniac facial’ that incorporates massage into a facial. It’s not just for aesthetics,
but for total body health. When you’re prone to water retention and puffiness, that’s an accumulation of
excess lymphatic fluid. We follow the Ayurvedic view that lymphatic stagnation leads to other
accumulation and dysfunction of the body. We also do breast massage. There is a lot of stagnation in
that area because we don’t touch it a lot. The main site of lymph is in the underarm, so we do that, too.”
KRISTEN MA, author, Beauty: Pure + Simple, Toronto
“Lymphatic drainage is effective when the lymphatic system is not responding physiologically. The
studies have not been done on healthy people, but I would suspect that the same intervention will not
increase lymphatic flow beyond what the body requires. The system auto-regulates and is very efficient
when not diseased. Cellulite is not fluid. It’s stored fat. No amount of stimulation is going to change
that. I understand that this treatment is offered in ‘health spas’ for otherwise healthy individuals, but it’s
unlikely that somebody who went through the 180 hours of additional training to get this certification
would use it to treat healthy people.”
STANLEY ROCKSON, Lymphatic Research Foundation advisory board, Stanford, California
“We use the Vodder method of manual lymph drainage (MLD). We lightly manoeuvre the skin to
motivate the fluid to move toward the nearest lymph nodes. Normally, the system does this by itself, but
we help increase the speed of drainage. In a medical setting, the method is used for lymphedema
management, venous congestion, burn patients, ulceration. It’s also used for sprains and strains,
fractures or chronic pain, as with fibromyalgia, migraines, whiplash or tension headaches. It can be
helpful for acne, rosacea, eczema.”
ROBERT HARRIS, director, Dr. Vodder School, Victoria, BC
“Lymphatic drainage is helpful for edema as well as skin issues like scars and acne. When we have
acne, the hair follicles are filled with oil and bacteria. A lymphatic massage decreases pain and swelling.
There are contraindications. These are malignant disease, acute inflammation with infection – because
you can spread that around – and acute allergic reactions. It’s very relaxing, because it’s totally
different from Swedish or deep tissue massage. It’s very gentle.”
THERESA CROLLY, registered massage therapist, Toronto
http://www.nowtoronto.com/lifestyle/story.cfm?content=174399
-----------
A Century-Old Puzzle Comes Together, Scientists ID Potential Protein Trigger In Lung Disease
Sarcoidosis - 04 May 2010
Lung researchers at Johns Hopkins have identified a possible protein trigger responsible for
sarcoidosis, a potentially fatal inflammatory disease marked by tiny clumps of inflammatory cells that
each year leave deep, grainy scars on the lungs, lymph nodes, skin and almost all major organs in
hundreds of thousands of Americans.
The disorder, whose cause has been a persistent mystery for nearly a century, strikes mostly young
adults and disproportionately affects African Americans.
The link between sarcoidosis and overproduction of the suspected protein trigger, called serum amyloid
A, was revealed after a six-year investigation encompassing more than two dozen laboratory
experiments, including some on diseased lung tissue samples from 86 patients in the Baltimore area.
"The increase in production of serum amyloid A explains for the first time how inflammation can persist
in the lungs without being triggered by an active infection," says study senior investigator and
pulmonologist David Moller, M.D., a professor at the Johns Hopkins University School of Medicine.
Moller is also director of the sarcoidosis clinic at The Johns Hopkins Hospital.
Study lead investigator Edward Chen, M.D., says the new findings also clear the path for developing
drug treatments or vaccines that can block serum amyloid A from binding to cell receptors and kicking
off inflammation.
In the short term, however, Moller says his team has plans to use the study results to create diagnostic
tests that could better predict which people with the disease are likely to heal on their own or are more
likely to suffer persistent inflammation, which can lead to scarring, difficulty breathing, and heart failure
that can only be fixed by lung transplantation.
In a report published in February in the American Journal of Respiratory and Critical Care Medicine,
the Johns Hopkins scientists described their research on what was behind the microscopic clusters of
inflamed tissue and white blood cells, or granulomas, which are a defining feature of sarcoidosis.
Such lung lesions are not unique to sarcoidosis and can be triggered by infections, such as in
tuberculosis, which is often confused with sarcoidosis. But unlike tuberculosis, sarcoidosis is not an
infectious disease, does not yield to antibiotics, and is not limited to any particular organ, occurring as
well in the eyes, skin, brain, heart and liver.
Of particular interest to researchers was the role played by so-called amyloids, a set of proteins known
to cause other persistent inflammatory conditions, such as amyloidosis. Indeed, a different kind of
amyloid has been tied to plaques in the brain tissue of people with Alzheimer's disease.
Key among the researchers' findings in sarcoidosis patients was that serum amyloid A stood out
because it was heavily concentrated within the granulomas in diseased and scarred lung tissue.
Researchers found the protein a hundred to a thousand times more widespread in sarcoidosis tissue
samples than in samples from people with tuberculosis, another granuloma-forming lung disease.
Similarly elevated amyloid levels were seen in comparison tests with tissue samples from people with
lung cancer and Crohn's disease.
Further tests in patients' lung cell cultures showed that adding serum amyloid A spiked production of at
least a half-dozen key inflammatory chemicals known to be involved in damaging tissue.
In another series of experiments in mice, the team discovered that granuloma formation in the lungs
sped up when the mice were given injections of synthetic serum amyloid A. Mice had previously been
injected with specially coated plastic beads designed to trigger sarcoidosis-like lesions. Adding the
synthetic protein led to the same biochemical reactions in the mice as observed in humans, suggesting to
the researchers that serum amyloid A played a key role in triggering sarcoidosis.
To better understand how serum amyloid A might be driving granuloma formation, the team used
special antibodies to block various cell surface receptor sites where the protein would bind to the white
blood cells and spur inflammation. Tests in human lung cells showed that blocking one particular
receptor, toll-like receptor-2 (TLR2), inhibited the sustained inflammatory reaction typically associated
with sarcoidosis. But when left to bind on its own, without an antibody blocking TLR2, the open
receptor could attach to serum amyloid A, and raised production of inflammatory chemicals would
ensue.
"Not only have we shown that serum amyloid A is a key protein trigger in sarcoidosis, but we also have
evidence that the resulting inflammation is dependent on binding the protein at toll-like receptor-2,
which opens up a host of possibilities that drugs blocking this binding site could prove an effective
treatment for this disease," says Chen, an assistant professor at Johns Hopkins.
Funding support for the report and research was provided by the National Institutes of Health, the
American Thoracic Society, the Foundation for Sarcoidosis Research, the Life and Breath Foundation,
and the Hospital for the Consumptives of Maryland (Eudowood.)
In addition to Moller and Chen, other Johns Hopkins researchers involved in this study were Zhimin
Song, M.D.; Matthew Willett, B.S.; Shannon Heine, B.S.; Rex Yung, M.D.; Mark Liu, M.D.; Steve
Groshong, M.D., Ph.D.; Ying Zhang, M.D., Ph.D.; and Rubin Tuder, M.D.
Source: Johns Hopkins Medicine
------------
June 25, 2010 - Decongestive Physiotherapy Helps Patients With Painful Leg Swelling –
For patients with painful swelling of the legs caused by chronic venous insufficiency (CVI), a
combination treatment approach called "complete decongestive physiotherapy" improves symptoms,
walking ability, and quality of life, reports a study in Topics in Geriatric Rehabilitation. The journal is
published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of
information and business intelligence for students, professionals, and institutions in medicine, nursing,
allied health, and pharmacy.
Complete (or "complex") decongestive physiotherapy (CDP) can greatly reduce leg swelling and pain
in patients with CVI, according to the new study, led by Yesim Bakar, Ph.D., P.T., of Abant Izzet
Baysal University in Bolu, Turkey. Another paper in the same issue of TGR shows similar benefits of
CDP in a patient with lymphatic obstruction (lymphedema) related to the skin condition psoriasis.
Complete Decongestive Physiotherapy Brings Good Results
Dr Bakar and coauthors evaluated the effects of CDP in 62 older adults (average age 65 years) with
CVI. Patients with CVI have poor blood flow in the veins of the leg, leading to fluid buildup. This
results in painful swelling, making it difficult for patients to walk and perform other activities. Usually
only one leg is affected.
All patients were treated using the CDP approach, which combines four types of physical therapy
treatments:
-- Manual lymph drainage massage to promote drainage of the lymph nodes.
-- Skin care moisturizers and other treatments for skin changes caused by poor circulation.
-- Compression bandages are applied to prevent fluid from reaccumulating.
-- Exercise simple leg exercises to improve blood flow and leg motion.
For the first month, patients met with a physical therapist five days a week for treatment. They also
received education in performing each of the four types of therapy for themselves. The goal was to
keep fluid buildup under control through lifelong, daily self-care.
The CDP treatment program dramatically reduced leg swelling on average, fluid buildup in the affected
leg decreased by the equivalent of nearly half a liter. Pain was also decreased, from an average score of
67 to 18 on a 100-point scale. Patients had improved walking ability, less pain when walking, and
improved ability to perform daily activities. The authors believe that including exercise in the treatment
program was a key factor in improving walking ability.
Dr. Bakar is also a co-author of the other paper, which reports on the use of CDP in a woman with
lymphedema related to the chronic skin condition psoriasis. In patients with lymphedema, obstruction of
the lymph nodes causes similar symptoms of leg pain and swelling. In both the short and long term,
CDP brought significant improvement in pain, swelling, and activity.
Inconclusive Results From Research Into Biologics-Associated Cancer Risk - 18 June 2010
Biologics-naive Juvenile Idiopathic Arthritis (JIA) patients may have an increased risk of cancer
compared with the general Swedish population, according to research presented at EULAR 2010, the
Annual Congress of the European League Against Rheumatism in Rome, Italy. Results of an additional
study, which researched a small cohort of patients showed an increased frequency of cancer in those
receiving the biologic etanercept, however, results were deemed not statistically significant by
researchers.
The results of a population-based Swedish cohort study found that the incidence of cancer among
paediatric patients with JIA identified during the last 40 years was comparable to that seen in the
general population, (0.5 vs. 0.4 cases per 1000 person years, Relative Risk (RR)=1.1, 95%CI 0.9-
1.5). Subset analyses however indicated that subjects diagnosed with JIA since 1987 (the year that the
Swedish patient registry attained nationwide coverage) were at elevated risk of developing cancer
(RR=2.3, 95%CI 1.2-4.4, 13 JIA cancers vs. 30 in comparator), attributed to an increased
occurrence of cancers of the lymphatic system (RR=4.2, 95%CI 1.7-10.7, 8 cancers in JIA vs. 10 in
comparator).
"These results are intriguing and suggest that in the past 20 years, patients with JIA not treated with
biological therapies appear to have an elevated risk of cancer compared with the general population,"
said lead author of the study Dr. Julia Simard, Clinical Epidemiology Unit, Karolinska Institute,
Stockholm, Sweden. "The results of our study indicate that evaluation of cancer risks with biologics in
paediatric populations need to factor in differences in incidence of cancer between these patients and
the general population. From a clinical point of view, it should be remembered that although we noted
an increased risk in relative terms, the excess risks remain low in absolute terms."
The Swedish study assessed a national JIA cohort of 9,020 patients. For each JIA patient, up to five
general-population comparators were identified (n=44,858). In the biologics-naïve JIA cohort, 60
cancers were observed during 131,144 person-years compared to 266 cancers during 661,758
person-years in the population comparator. Researchers noted that sensitivity analyses did not reveal
an explanation for the differences seen between patients identified before and after 1987.
The results of the second study combined data on 1,721 patients treated with etanercept from three
prospective JIA registries in Germany, the UK and the US. Of the 1,641 patients who qualified for the
primary analysis, two cancers were reported. Whilst this yielded a rate higher than expected when
compared to the general population, it was not statistically significant (RR estimated using a
Standardized Incident Ratio (SIR) of 3.7 (0.5-13.4, 95%CI)). This is believed to be in part due to the
low event rate. The interpretation of these findings may be further limited by the fact that the
comparator rates were based on a general population and not a biologics-naïve JIA population, as per
the Swedish study, which suggests this may indicate an increased underlying risk of cancer.
Abstract Numbers: OP0086 & OP0274
Source:
Caroline Butt
European League Against Rheumatism
July 14, 2010 - Protalix BioTherapeutics Receives PDUFA Date For Taliglucerase Alfa -
Protalix BioTherapeutics, Inc. (NYSE-Amex: PLX), announced that the Company's New Drug
Application (NDA) for taliglucerase alfa has been accepted for review by the U.S. Food and Drug
Administration (FDA). The FDA granted taliglucerase alfa a standard review time of ten months,
assigning a Prescription Drug User Fee Act (PDUFA) action date of February 25, 2011. Taliglucerase
alfa is the Company's proprietary plant cell expressed recombinant form of human Glucocerebrosidase
(GCD) which is being developed for the treatment of Gaucher disease under a Special Protocol
Assessment (SPA) with the FDA. Following the completion of a phase III clinical trial of taliglucerase
alfa, the Company completed the submission of a rolling NDA with the FDA in April 2010.
"If approved, taliglucerase alfa will be an attractive and important therapeutic option for Gaucher
patients," said Dr. David Aviezer, President and Chief Executive Officer of Protalix. "We look forward
to working closely with the agency through this final stage of the review process."
Taliglucerase alfa has been granted orphan drug designation from the FDA in the United States. The
Company continues to make taliglucerase alfa available to Gaucher patients in the United States under
an Expanded Access protocol, as well as 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 1 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™ presents a proprietary method for the expression of
recombinant proteins that Protalix believes will allow for the cost-effective, 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. 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.
August 5, 2010 - Ease The Aftermath Of Breast Cancer With New Imaging Technique -
A new study of breast cancer survivors may help physicians ease a common side effect of cancer
treatments. The collaborative research by Eva Sevick, Ph.D., Director of the Center for Molecular
Imaging at the University of Texas Health Science Center in Houston (UTHSC), and Caroline Fife, M.
D., Director of the Memorial Herman Wound Care Clinic at UTHSC, could bring relief to millions.
Their paper appears in the inaugural issue of Biomedical Optics Express, an online, open-access
journal published by the Optical Society (OSA). The papers featured in the journal will encompass
theoretical modeling and simulations, technology development, biomedical studies and clinical
applications.
A substantial number of breast cancer survivors suffer from lymphedema in the aftermath of their cancer
surgeries. In lymphedema, fluids accumulate in the arms, potentially causing disfiguring and debilitating
swelling that can impact quality of life.
Treatments vary, but they generally consist of using manual and pneumatic therapies to "push" or
stimulate the body to remove excess fluid and reduce tissue swelling. Finding out whether a treatment is
working can take months. That's because the current method of assessing progress is to measure the
circumference or volume of a limb and check for changes in swelling - and a size change big enough to
be measured takes time.
During this time, the condition might improve - or it might worsen.
The UTHSC research team has developed what promises to be a more sensitive and more immediate
way to monitor the effectiveness of a treatment. Their new near-infrared fluorescence imaging technique
examines the root cause of lymphedema: blockages or damages in the lymphatic system that prevent
fluid from circulating through the body and cause it to pool in the limbs.
"The lymphatics are like the sewer system of your body," says Sevick. "If they get all plugged up, then
there's a flood."
Nine women - six with lymphedema and three controls - were injected with a near-infrared fluorescent
dye that has been used safely for 50 years at much higher dosages. The dye is taken up by the
lymphatic system. When tissue surfaces are exposed to a dim, near-infrared laser - harmless to the
human body - the dye within fluoresces, revealing its transit through the lymphatic system.
"This is the only method that can directly check for improvements in lymphatic function in one sitting,
before and after a treatment," says Sevick.
Physicians have several treatment options for controlling lymphedema. They may use compression
bandages and massage limbs to manually encourage fluids to drain from the arm. Pneumatic
compression devices, sleeves made of segmented chambers that inflate and squeeze, may provide a
similar benefit at home, but they may not always be covered by Medicare reimbursements because of
lacking direct evidence of their benefit.
"The problem is that there has been no good way to measure direct evidence of benefit," says Sevick.
"Hopefully we can use near-infrared fluorescence imaging technique to show improved lymphatic
function from these treatments."
The NIR fluorescence technique detected statistically significant improvements in fluid flow through the
lymphatic system immediately after the use of pneumatic compression devices. A larger follow-up study
will be needed to confirm the results of this pilot study, says Sevick.
The research was funded by the National Institutes of Health and by Tactile Systems Technology, Inc.,
which manufactures and markets the Flexitouch pneumatic compression devices tested in this research.
The paper:
"Direct evidence of lymphatic function improvement after advanced pneumatic compression device
treatment of lymphedema" by Kristen E. Adams et al.
Source:
Lyndsay Basista
Optical Society of America
August 12, 2010 - HemaQuest Pharmaceuticals Initiates Phase 2 Clinical Trial In EBV-Related
Malignancies -
HemaQuest Pharmaceuticals announced that it has initiated the Company's Phase 2 clinical trial
evaluating its proprietary HQK-1004 therapy for the treatment of lymphomas and related cancers
associated with Epstein-Barr virus (EBV) infection. These EBV-related cancers have poor prognoses
and short patient survival. Currently available cancer therapies are typically much less effective in
patients with EBV-related lymphoid malignancies than in patients who have similar cancers not infected
with the virus.
In a Phase 1 clinical trial previously conducted by HemaQuest's scientific founders, 15 patients with
relapsed or refractory EBV-related lymphomas were treated with a 3-week infusion of our proprietary
therapy, HQK-1004 and the anti-viral drug, Ganciclovir (GCV). Ten patients (67% response rate)
demonstrated objective tumor responses, including several patients with complete tumor responses.
This study provided support for previous laboratory studies demonstrating that HQK 1004 makes
EBV infected cancers susceptible to antiviral therapy.
HQK-1004 acts by inducing the expression of a gene for a viral protein that is the target of several
common anti-viral drugs, including GCV, which eradicate virally infected cells. The gene that makes this
target protein is present in EBV infected tumor cells, but it is not expressed, thus rendering these cells
resistant to anti-viral therapeutics. To overcome this problem, HemaQuest has developed a proprietary
therapeutic approach using HQK-1004, which enables the expression of the viral protein that is the
target of anti-viral drugs. Combining HQK-1004 with anti-viral therapeutics now enables the killing of
viral-infected tumor cells, while uninfected cells should not be affected.
In the current Company-sponsored Phase 2 clinical trial, up to 40 patients with advanced EBV-related
lymphoid malignancies will be treated with HQK-1004 and GCV at several clinical sites in the US and
abroad. The trial will test whether a shorter, 5-day infusion of HQK-1004 can reproduce the promising
results documented in the first clinical trial. With positive clinical results, the Company plans additional
studies to obtain FDA approval for this clinical indication. In addition, HemaQuest intends to test this
therapeutic approach to treat other viral-related cancers.
"This trial represents an important step forward in the development of our HQK-1004 therapy and
builds on the existing clinical safety and efficacy data," commented Susan Perrine, MD, Chief Scientific
Officer and VP of Clinical Affairs at HemaQuest. "Our targeted therapy represents a novel approach to
treating viral-related cancers, which include up to 20% of malignancies. By targeting the virus
associated with the tumor cells, the toxic side effects that commonly occur with traditional
chemotherapy are potentially avoided."
Added Ronald Berenson, MD, President and Chief Executive Officer of HemaQuest, "We are very
pleased to announce the start of this global Phase 2 trial. HQK-1004 has the potential to improve the
outcome of patients with EBV lymphoid malignancies, most of whom have poor responses and limited
survival with current therapies. If this trial is successful, it could lead to a new approach to treating viral-
related cancers, including other hematologic malignancies as well as solid tumors."
Source: HemaQuest Pharmaceuticals
August 24, 2010 - Two-Year Data From Phase 2 Trial Of Genzyme's Eliglustat Tartrate For Gaucher
Disease To Be Published In The Journal Blood -
Genzyme Corporation (NASDAQ: GENZ) announced that the two-year follow-up results from the
phase 2 clinical trial of its investigational therapy known as eliglustat tartrate have been accepted for
publication in the journal Blood. The results have been pre-published on the journal's website and are
available to subscribers.
Eliglustat tartrate, a capsule taken orally, is being developed to provide a convenient treatment
alternative for adult patients with Gaucher disease type 1, and to offer a broader range of treatment
options for patients and physicians to achieve individual therapeutic goals. Current treatments, including
Genzyme's Cerezyme® (imiglucerase for injection), the standard of care for patients with Gaucher
disease type 1, are administered through intravenous infusions.
Genzyme reported last year that the 52-week phase 2 trial of eliglustat tartrate had met its primary
composite endpoint: a clinically meaningful response in at least two of three endpoints (improvements in
spleen size, hemoglobin and platelet levels) in individual patients. The two-year data to be published in
Blood indicate continued improvements across all endpoints. After two years, most patients (85%) had
met at least three of the four hematologic and visceral therapeutic goals established for enzyme
replacement therapy. These data also suggest that eliglustat tartrate may positively impact two
indicators of bone disease, bone mineral density and the presence of dark marrow.
The most common adverse events reported in greater than 10 percent of patients included viral
infections (six patients), urinary tract infections, increased blood pressure, and abdominal pain (three
patients each). Eight drug-related adverse events, including one serious event, were reported in six
patients. All were mild in severity.
These two-year results were presented at the Lysosomal Disease Network WORLD Symposium
earlier this year.
Phase 3 Program
Genzyme is currently enrolling patients in three global, multi-center, phase 3 trials of eliglustat tartrate.
Combined, more than 450 patients are expected to participate, making this the largest clinical program
ever focused on Gaucher disease. Over 50 sites in more than 25 countries are currently participating,
with additional centers planned.
The first phase 3 trial, ENCORE, is a randomized, open-label study for adult patients with Gaucher
disease type 1, designed to compare eliglustat tartrate to Cerezyme. Adult patients who have
previously received enzyme replacement therapy for at least three years and have reached their
therapeutic goals may qualify for this trial. The second trial, ENGAGE, is a randomized, double-blind,
placebo-controlled study for patients with a confirmed diagnosis of Gaucher disease type 1. Patients
who have not received enzyme replacement therapy within 9 months or substrate reduction therapy
within 6 months of participation may qualify for this study. Genzyme recently launched a third trial,
known as EDGE, to compare once-daily dosing of eliglustat tartrate with twice-daily dosing.
Breast Cancer Survivors Don't Need To Be Afraid Of Air Travel: U Of A Study - 21 August 2010
University of Alberta researcher Margie McNeely says results from an international study she was part
of indicates certain precautions about the risk of lymphedema for breast cancer survivors are outdated.
McNeely, from the Faculty of Rehabilitation Medicine, says women who've had breast cancer surgery
are often warned that pressure changes in an airplane cabin could trigger lymphedema, chronic swelling
in the arm. But the study she did with an Australian research team showed that only five per cent of
these women are likely at risk of developing any arm swelling when flying.
The caution about lymphedema risk is for women who have had lymph nodes removed from the
armpit, a common procedure during cancer treatment. McNeely says because these lymph nodes help
drain fluid when they are removed there is the potential for chronic swelling.
McNeely teamed up with Australian researcher Sharon Kilbreath to study the effect of air travel on 60
Canadian breast cancer survivors who were flying to Australia for an International Dragon Boat
Festival. Seventeen of these women were from Edmonton. The study also involved a group of 12
women who were travelling to the festival from different areas of Australia.
The researchers compared both of the participants' arms, the arm where lymph nodes were removed
from the armpit and the opposite unaffected arm, with a device that can detect subtle changes in fluid
difference between the arms. The measurements were done in Canada before they left and again in
Australia when they arrived.
Findings indicate that 95 per cent of the women had no arm swelling. Four women had a slight increase
but at a follow-up test, done six weeks after the women returned to Canada, three were back to
normal and only one woman was found at possible risk for chronic swelling.
McNeely says that, until now, information about air travel and lymphedema risk has not been based on
solid evidence, but says this research shows that while there is a risk of developing lymphedema during
flight, that risk is very low.
McNeely's research was published in the journal Breast Cancer Research and Treatment.
August 27, 2010 - Shire Announces European Approval Of VPRIV(R) (velaglucerase Alfa) For The
Treatment Of Type 1 Gaucher Disease –
Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company,
announced that the European Commission has granted marketing authorisation for VPRIV(R)
(velaglucerase alfa), a human cell line derived enzyme replacement therapy (ERT) for the long-term
treatment of type 1 Gaucher disease. VPRIV has been authorized as an orphan medicine through the
Centralised Procedure, making it available in 30 countries across Europe.
This approval was based on data from Shire's velaglucerase alfa clinical development programme
which represents the largest and most comprehensive clinical data set supporting registration for an
ERT for type 1 Gaucher disease. In total, over 100 Gaucher patients at 24 sites in 10 countries around
the world participated in the clinical studies, all of which met their primary endpoints.
"Gaucher disease is a rare and often debilitating condition," said Professor Tim Cox from the
Department of Medicine, University of Cambridge, and founder of the largest U.K. Gaucher clinic at
Addenbrooke's Hospital. "The European approval of VPRIV is important in that we now have an
alternative, licensed therapeutic enzyme. For type 1 patients the availability of VPRIV provides further
opportunities to individualise treatment options for this complex disorder."
Across Europe, hundreds of type 1 Gaucher patients have been receiving velaglucerase alfa through
early access programmes, developed in partnership with national authorities, Gaucher expert physicians
and patient associations. Globally there are over 850 patients on velaglucerase alfa and demand
continues to be strong. As a result, Shire has implemented a program to carefully monitor demand and
manage requests from physicians and patients in order to ensure long-term, uninterrupted treatment
with VPRIV.
"The Marketing Authorisation for VPRIV in the EU is an important milestone for Shire," said Sylvie
Gregoire, President, Shire Human Genetic Therapies. "Our efforts to accelerate our manufacturing,
clinical and regulatory timelines have resulted in VPRIV's approval in Europe and the US months ahead
of schedule."
Important Safety Information
The most serious adverse reactions in patients treated 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. Other commonly observed
adverse reactions in >10% of patients were: abdominal pain, back pain, joint pain, upper respiratory
tract infection, and activated partial thromboplastin time prolonged. Adverse reactions more commonly
seen in paediatric patients (>10% difference) included upper respiratory tract infection, rash, activated
partial thromboplastin time prolonged, and pyrexia. In clinical trials one patient developed neutralizing
antibodies.
September 1, 2010 - BioMarin Receives Orphan Drug Designation From The FDA For BMN-701
For The Treatment Of Pompe Disease -
BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) announced that it has received orphan drug
designation from the U.S. Food and Drug Administration (FDA) for BMN-701, a novel fusion of
insulin-like growth factor 2 and alpha glucosidase (IGF2-GAA) in development for the treatment of
Pompe disease. An investigational new drug application (IND) for BMN-701 has been submitted,
investigational material has been manufactured and a Phase I/II study is expected to start in the first
quarter of 2011.
"Receiving orphan drug designation from the FDA for BMN-701 is a significant milestone for our
Pompe program. As part of their assessment for designation, the FDA determined that BMN-701 is
sufficiently different from alglusidase alfa (Myozyme/Lumizyme) to allow for a unique orphan
designation. For this reason, clinical superiority over alglusidase alfa will not be necessary to secure
orphan exclusivity for BMN-701," said Jean-Jacques Bienaime, Chief Executive Officer of BioMarin.
"This emphasizes our mission of developing innovative, products for orphan diseases with an unmet
medical need. We believe BMN-701 has the potential to possibly deliver more enzyme to lysosomes
compared to traditional mannose-6-phosphate targeted approaches using the recently acquired GILT
technology."
About Pompe Disease
Pompe disease, a lysosomal storage disorder, is a progressive degenerative disease of the heart
muscle, diaphragm and skeletal muscle. It is caused by a deficiency in the lysosomal enzyme acid alpha
glucosidase which leads to the accumulation of glycogen in myocyte lysosomes and results in cell death.
The incidence is one in 40,000 births. There are two main forms of Pompe disease: adult onset with an
incidence of one in 57,000 births and infantile onset with an incidence of one in 138,000 births. The
current standard of care is Genzyme's Myozyme and Lumizyme. Prognosis with standard of care is
stabilization of the disease or minor improvements for the majority of adult onset patients.
About BioMarin
BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical
conditions. The company's product portfolio comprises four approved products and multiple clinical
and pre-clinical product candidates. Approved products include Naglazyme® (galsulfase) for
mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin;
Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed
through a 50/50 joint venture with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride)
Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck
KGaA of Darmstadt, Germany; and Firdapse™ (amifampridine phosphate), which has been approved
by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS).
Other product candidates include GALNS (N-acetylgalactosamine 6-sulfatase), which is currently in
clinical development for the treatment of MPS IVA and PEG-PAL (PEGylated recombinant
phenylalanine ammonia lyase), which is currently in Phase II clinical development for the treatment of
PKU.
A Century-Old Puzzle Comes Together, Scientists ID Potential Protein Trigger In Lung Disease
Sarcoidosis - 04 May 2010
Lung researchers at Johns Hopkins have identified a possible protein trigger responsible for
sarcoidosis, a potentially fatal inflammatory disease marked by tiny clumps of inflammatory cells that
each year leave deep, grainy scars on the lungs, lymph nodes, skin and almost all major organs in
hundreds of thousands of Americans.
The disorder, whose cause has been a persistent mystery for nearly a century, strikes mostly young
adults and disproportionately affects African Americans.
The link between sarcoidosis and overproduction of the suspected protein trigger, called serum amyloid
A, was revealed after a six-year investigation encompassing more than two dozen laboratory
experiments, including some on diseased lung tissue samples from 86 patients in the Baltimore area.
"The increase in production of serum amyloid A explains for the first time how inflammation can persist
in the lungs without being triggered by an active infection," says study senior investigator and
pulmonologist David Moller, M.D., a professor at the Johns Hopkins University School of Medicine.
Moller is also director of the sarcoidosis clinic at The Johns Hopkins Hospital.
Study lead investigator Edward Chen, M.D., says the new findings also clear the path for developing
drug treatments or vaccines that can block serum amyloid A from binding to cell receptors and kicking
off inflammation.
In the short term, however, Moller says his team has plans to use the study results to create diagnostic
tests that could better predict which people with the disease are likely to heal on their own or are more
likely to suffer persistent inflammation, which can lead to scarring, difficulty breathing, and heart failure
that can only be fixed by lung transplantation.
In a report published in February in the American Journal of Respiratory and Critical Care Medicine,
the Johns Hopkins scientists described their research on what was behind the microscopic clusters of
inflamed tissue and white blood cells, or granulomas, which are a defining feature of sarcoidosis.
Such lung lesions are not unique to sarcoidosis and can be triggered by infections, such as in
tuberculosis, which is often confused with sarcoidosis. But unlike tuberculosis, sarcoidosis is not an
infectious disease, does not yield to antibiotics, and is not limited to any particular organ, occurring as
well in the eyes, skin, brain, heart and liver.
Of particular interest to researchers was the role played by so-called amyloids, a set of proteins known
to cause other persistent inflammatory conditions, such as amyloidosis. Indeed, a different kind of
amyloid has been tied to plaques in the brain tissue of people with Alzheimer's disease.
Key among the researchers' findings in sarcoidosis patients was that serum amyloid A stood out
because it was heavily concentrated within the granulomas in diseased and scarred lung tissue.
Researchers found the protein a hundred to a thousand times more widespread in sarcoidosis tissue
samples than in samples from people with tuberculosis, another granuloma-forming lung disease.
Similarly elevated amyloid levels were seen in comparison tests with tissue samples from people with
lung cancer and Crohn's disease.
Further tests in patients' lung cell cultures showed that adding serum amyloid A spiked production of at
least a half-dozen key inflammatory chemicals known to be involved in damaging tissue.
In another series of experiments in mice, the team discovered that granuloma formation in the lungs
sped up when the mice were given injections of synthetic serum amyloid A. Mice had previously been
injected with specially coated plastic beads designed to trigger sarcoidosis-like lesions. Adding the
synthetic protein led to the same biochemical reactions in the mice as observed in humans, suggesting to
the researchers that serum amyloid A played a key role in triggering sarcoidosis.
To better understand how serum amyloid A might be driving granuloma formation, the team used
special antibodies to block various cell surface receptor sites where the protein would bind to the white
blood cells and spur inflammation. Tests in human lung cells showed that blocking one particular
receptor, toll-like receptor-2 (TLR2), inhibited the sustained inflammatory reaction typically associated
with sarcoidosis. But when left to bind on its own, without an antibody blocking TLR2, the open
receptor could attach to serum amyloid A, and raised production of inflammatory chemicals would
ensue.
"Not only have we shown that serum amyloid A is a key protein trigger in sarcoidosis, but we also have
evidence that the resulting inflammation is dependent on binding the protein at toll-like receptor-2,
which opens up a host of possibilities that drugs blocking this binding site could prove an effective
treatment for this disease," says Chen, an assistant professor at Johns Hopkins.
Funding support for the report and research was provided by the National Institutes of Health, the
American Thoracic Society, the Foundation for Sarcoidosis Research, the Life and Breath Foundation,
and the Hospital for the Consumptives of Maryland (Eudowood.)
In addition to Moller and Chen, other Johns Hopkins researchers involved in this study were Zhimin
Song, M.D.; Matthew Willett, B.S.; Shannon Heine, B.S.; Rex Yung, M.D.; Mark Liu, M.D.; Steve
Groshong, M.D., Ph.D.; Ying Zhang, M.D., Ph.D.; and Rubin Tuder, M.D.
Source: Johns Hopkins Medicine
------------
June 25, 2010 - Decongestive Physiotherapy Helps Patients With Painful Leg Swelling –
For patients with painful swelling of the legs caused by chronic venous insufficiency (CVI), a
combination treatment approach called "complete decongestive physiotherapy" improves symptoms,
walking ability, and quality of life, reports a study in Topics in Geriatric Rehabilitation. The journal is
published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of
information and business intelligence for students, professionals, and institutions in medicine, nursing,
allied health, and pharmacy.
Complete (or "complex") decongestive physiotherapy (CDP) can greatly reduce leg swelling and pain
in patients with CVI, according to the new study, led by Yesim Bakar, Ph.D., P.T., of Abant Izzet
Baysal University in Bolu, Turkey. Another paper in the same issue of TGR shows similar benefits of
CDP in a patient with lymphatic obstruction (lymphedema) related to the skin condition psoriasis.
Complete Decongestive Physiotherapy Brings Good Results
Dr Bakar and coauthors evaluated the effects of CDP in 62 older adults (average age 65 years) with
CVI. Patients with CVI have poor blood flow in the veins of the leg, leading to fluid buildup. This
results in painful swelling, making it difficult for patients to walk and perform other activities. Usually
only one leg is affected.
All patients were treated using the CDP approach, which combines four types of physical therapy
treatments:
-- Manual lymph drainage massage to promote drainage of the lymph nodes.
-- Skin care moisturizers and other treatments for skin changes caused by poor circulation.
-- Compression bandages are applied to prevent fluid from reaccumulating.
-- Exercise simple leg exercises to improve blood flow and leg motion.
For the first month, patients met with a physical therapist five days a week for treatment. They also
received education in performing each of the four types of therapy for themselves. The goal was to
keep fluid buildup under control through lifelong, daily self-care.
The CDP treatment program dramatically reduced leg swelling on average, fluid buildup in the affected
leg decreased by the equivalent of nearly half a liter. Pain was also decreased, from an average score of
67 to 18 on a 100-point scale. Patients had improved walking ability, less pain when walking, and
improved ability to perform daily activities. The authors believe that including exercise in the treatment
program was a key factor in improving walking ability.
Dr. Bakar is also a co-author of the other paper, which reports on the use of CDP in a woman with
lymphedema related to the chronic skin condition psoriasis. In patients with lymphedema, obstruction of
the lymph nodes causes similar symptoms of leg pain and swelling. In both the short and long term,
CDP brought significant improvement in pain, swelling, and activity.
Inconclusive Results From Research Into Biologics-Associated Cancer Risk - 18 June 2010
Biologics-naive Juvenile Idiopathic Arthritis (JIA) patients may have an increased risk of cancer
compared with the general Swedish population, according to research presented at EULAR 2010, the
Annual Congress of the European League Against Rheumatism in Rome, Italy. Results of an additional
study, which researched a small cohort of patients showed an increased frequency of cancer in those
receiving the biologic etanercept, however, results were deemed not statistically significant by
researchers.
The results of a population-based Swedish cohort study found that the incidence of cancer among
paediatric patients with JIA identified during the last 40 years was comparable to that seen in the
general population, (0.5 vs. 0.4 cases per 1000 person years, Relative Risk (RR)=1.1, 95%CI 0.9-
1.5). Subset analyses however indicated that subjects diagnosed with JIA since 1987 (the year that the
Swedish patient registry attained nationwide coverage) were at elevated risk of developing cancer
(RR=2.3, 95%CI 1.2-4.4, 13 JIA cancers vs. 30 in comparator), attributed to an increased
occurrence of cancers of the lymphatic system (RR=4.2, 95%CI 1.7-10.7, 8 cancers in JIA vs. 10 in
comparator).
"These results are intriguing and suggest that in the past 20 years, patients with JIA not treated with
biological therapies appear to have an elevated risk of cancer compared with the general population,"
said lead author of the study Dr. Julia Simard, Clinical Epidemiology Unit, Karolinska Institute,
Stockholm, Sweden. "The results of our study indicate that evaluation of cancer risks with biologics in
paediatric populations need to factor in differences in incidence of cancer between these patients and
the general population. From a clinical point of view, it should be remembered that although we noted
an increased risk in relative terms, the excess risks remain low in absolute terms."
The Swedish study assessed a national JIA cohort of 9,020 patients. For each JIA patient, up to five
general-population comparators were identified (n=44,858). In the biologics-naïve JIA cohort, 60
cancers were observed during 131,144 person-years compared to 266 cancers during 661,758
person-years in the population comparator. Researchers noted that sensitivity analyses did not reveal
an explanation for the differences seen between patients identified before and after 1987.
The results of the second study combined data on 1,721 patients treated with etanercept from three
prospective JIA registries in Germany, the UK and the US. Of the 1,641 patients who qualified for the
primary analysis, two cancers were reported. Whilst this yielded a rate higher than expected when
compared to the general population, it was not statistically significant (RR estimated using a
Standardized Incident Ratio (SIR) of 3.7 (0.5-13.4, 95%CI)). This is believed to be in part due to the
low event rate. The interpretation of these findings may be further limited by the fact that the
comparator rates were based on a general population and not a biologics-naïve JIA population, as per
the Swedish study, which suggests this may indicate an increased underlying risk of cancer.
Abstract Numbers: OP0086 & OP0274
Source:
Caroline Butt
European League Against Rheumatism
July 14, 2010 - Protalix BioTherapeutics Receives PDUFA Date For Taliglucerase Alfa -
Protalix BioTherapeutics, Inc. (NYSE-Amex: PLX), announced that the Company's New Drug
Application (NDA) for taliglucerase alfa has been accepted for review by the U.S. Food and Drug
Administration (FDA). The FDA granted taliglucerase alfa a standard review time of ten months,
assigning a Prescription Drug User Fee Act (PDUFA) action date of February 25, 2011. Taliglucerase
alfa is the Company's proprietary plant cell expressed recombinant form of human Glucocerebrosidase
(GCD) which is being developed for the treatment of Gaucher disease under a Special Protocol
Assessment (SPA) with the FDA. Following the completion of a phase III clinical trial of taliglucerase
alfa, the Company completed the submission of a rolling NDA with the FDA in April 2010.
"If approved, taliglucerase alfa will be an attractive and important therapeutic option for Gaucher
patients," said Dr. David Aviezer, President and Chief Executive Officer of Protalix. "We look forward
to working closely with the agency through this final stage of the review process."
Taliglucerase alfa has been granted orphan drug designation from the FDA in the United States. The
Company continues to make taliglucerase alfa available to Gaucher patients in the United States under
an Expanded Access protocol, as well as 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 1 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™ presents a proprietary method for the expression of
recombinant proteins that Protalix believes will allow for the cost-effective, 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. 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.
August 5, 2010 - Ease The Aftermath Of Breast Cancer With New Imaging Technique -
A new study of breast cancer survivors may help physicians ease a common side effect of cancer
treatments. The collaborative research by Eva Sevick, Ph.D., Director of the Center for Molecular
Imaging at the University of Texas Health Science Center in Houston (UTHSC), and Caroline Fife, M.
D., Director of the Memorial Herman Wound Care Clinic at UTHSC, could bring relief to millions.
Their paper appears in the inaugural issue of Biomedical Optics Express, an online, open-access
journal published by the Optical Society (OSA). The papers featured in the journal will encompass
theoretical modeling and simulations, technology development, biomedical studies and clinical
applications.
A substantial number of breast cancer survivors suffer from lymphedema in the aftermath of their cancer
surgeries. In lymphedema, fluids accumulate in the arms, potentially causing disfiguring and debilitating
swelling that can impact quality of life.
Treatments vary, but they generally consist of using manual and pneumatic therapies to "push" or
stimulate the body to remove excess fluid and reduce tissue swelling. Finding out whether a treatment is
working can take months. That's because the current method of assessing progress is to measure the
circumference or volume of a limb and check for changes in swelling - and a size change big enough to
be measured takes time.
During this time, the condition might improve - or it might worsen.
The UTHSC research team has developed what promises to be a more sensitive and more immediate
way to monitor the effectiveness of a treatment. Their new near-infrared fluorescence imaging technique
examines the root cause of lymphedema: blockages or damages in the lymphatic system that prevent
fluid from circulating through the body and cause it to pool in the limbs.
"The lymphatics are like the sewer system of your body," says Sevick. "If they get all plugged up, then
there's a flood."
Nine women - six with lymphedema and three controls - were injected with a near-infrared fluorescent
dye that has been used safely for 50 years at much higher dosages. The dye is taken up by the
lymphatic system. When tissue surfaces are exposed to a dim, near-infrared laser - harmless to the
human body - the dye within fluoresces, revealing its transit through the lymphatic system.
"This is the only method that can directly check for improvements in lymphatic function in one sitting,
before and after a treatment," says Sevick.
Physicians have several treatment options for controlling lymphedema. They may use compression
bandages and massage limbs to manually encourage fluids to drain from the arm. Pneumatic
compression devices, sleeves made of segmented chambers that inflate and squeeze, may provide a
similar benefit at home, but they may not always be covered by Medicare reimbursements because of
lacking direct evidence of their benefit.
"The problem is that there has been no good way to measure direct evidence of benefit," says Sevick.
"Hopefully we can use near-infrared fluorescence imaging technique to show improved lymphatic
function from these treatments."
The NIR fluorescence technique detected statistically significant improvements in fluid flow through the
lymphatic system immediately after the use of pneumatic compression devices. A larger follow-up study
will be needed to confirm the results of this pilot study, says Sevick.
The research was funded by the National Institutes of Health and by Tactile Systems Technology, Inc.,
which manufactures and markets the Flexitouch pneumatic compression devices tested in this research.
The paper:
"Direct evidence of lymphatic function improvement after advanced pneumatic compression device
treatment of lymphedema" by Kristen E. Adams et al.
Source:
Lyndsay Basista
Optical Society of America
August 12, 2010 - HemaQuest Pharmaceuticals Initiates Phase 2 Clinical Trial In EBV-Related
Malignancies -
HemaQuest Pharmaceuticals announced that it has initiated the Company's Phase 2 clinical trial
evaluating its proprietary HQK-1004 therapy for the treatment of lymphomas and related cancers
associated with Epstein-Barr virus (EBV) infection. These EBV-related cancers have poor prognoses
and short patient survival. Currently available cancer therapies are typically much less effective in
patients with EBV-related lymphoid malignancies than in patients who have similar cancers not infected
with the virus.
In a Phase 1 clinical trial previously conducted by HemaQuest's scientific founders, 15 patients with
relapsed or refractory EBV-related lymphomas were treated with a 3-week infusion of our proprietary
therapy, HQK-1004 and the anti-viral drug, Ganciclovir (GCV). Ten patients (67% response rate)
demonstrated objective tumor responses, including several patients with complete tumor responses.
This study provided support for previous laboratory studies demonstrating that HQK 1004 makes
EBV infected cancers susceptible to antiviral therapy.
HQK-1004 acts by inducing the expression of a gene for a viral protein that is the target of several
common anti-viral drugs, including GCV, which eradicate virally infected cells. The gene that makes this
target protein is present in EBV infected tumor cells, but it is not expressed, thus rendering these cells
resistant to anti-viral therapeutics. To overcome this problem, HemaQuest has developed a proprietary
therapeutic approach using HQK-1004, which enables the expression of the viral protein that is the
target of anti-viral drugs. Combining HQK-1004 with anti-viral therapeutics now enables the killing of
viral-infected tumor cells, while uninfected cells should not be affected.
In the current Company-sponsored Phase 2 clinical trial, up to 40 patients with advanced EBV-related
lymphoid malignancies will be treated with HQK-1004 and GCV at several clinical sites in the US and
abroad. The trial will test whether a shorter, 5-day infusion of HQK-1004 can reproduce the promising
results documented in the first clinical trial. With positive clinical results, the Company plans additional
studies to obtain FDA approval for this clinical indication. In addition, HemaQuest intends to test this
therapeutic approach to treat other viral-related cancers.
"This trial represents an important step forward in the development of our HQK-1004 therapy and
builds on the existing clinical safety and efficacy data," commented Susan Perrine, MD, Chief Scientific
Officer and VP of Clinical Affairs at HemaQuest. "Our targeted therapy represents a novel approach to
treating viral-related cancers, which include up to 20% of malignancies. By targeting the virus
associated with the tumor cells, the toxic side effects that commonly occur with traditional
chemotherapy are potentially avoided."
Added Ronald Berenson, MD, President and Chief Executive Officer of HemaQuest, "We are very
pleased to announce the start of this global Phase 2 trial. HQK-1004 has the potential to improve the
outcome of patients with EBV lymphoid malignancies, most of whom have poor responses and limited
survival with current therapies. If this trial is successful, it could lead to a new approach to treating viral-
related cancers, including other hematologic malignancies as well as solid tumors."
Source: HemaQuest Pharmaceuticals
August 24, 2010 - Two-Year Data From Phase 2 Trial Of Genzyme's Eliglustat Tartrate For Gaucher
Disease To Be Published In The Journal Blood -
Genzyme Corporation (NASDAQ: GENZ) announced that the two-year follow-up results from the
phase 2 clinical trial of its investigational therapy known as eliglustat tartrate have been accepted for
publication in the journal Blood. The results have been pre-published on the journal's website and are
available to subscribers.
Eliglustat tartrate, a capsule taken orally, is being developed to provide a convenient treatment
alternative for adult patients with Gaucher disease type 1, and to offer a broader range of treatment
options for patients and physicians to achieve individual therapeutic goals. Current treatments, including
Genzyme's Cerezyme® (imiglucerase for injection), the standard of care for patients with Gaucher
disease type 1, are administered through intravenous infusions.
Genzyme reported last year that the 52-week phase 2 trial of eliglustat tartrate had met its primary
composite endpoint: a clinically meaningful response in at least two of three endpoints (improvements in
spleen size, hemoglobin and platelet levels) in individual patients. The two-year data to be published in
Blood indicate continued improvements across all endpoints. After two years, most patients (85%) had
met at least three of the four hematologic and visceral therapeutic goals established for enzyme
replacement therapy. These data also suggest that eliglustat tartrate may positively impact two
indicators of bone disease, bone mineral density and the presence of dark marrow.
The most common adverse events reported in greater than 10 percent of patients included viral
infections (six patients), urinary tract infections, increased blood pressure, and abdominal pain (three
patients each). Eight drug-related adverse events, including one serious event, were reported in six
patients. All were mild in severity.
These two-year results were presented at the Lysosomal Disease Network WORLD Symposium
earlier this year.
Phase 3 Program
Genzyme is currently enrolling patients in three global, multi-center, phase 3 trials of eliglustat tartrate.
Combined, more than 450 patients are expected to participate, making this the largest clinical program
ever focused on Gaucher disease. Over 50 sites in more than 25 countries are currently participating,
with additional centers planned.
The first phase 3 trial, ENCORE, is a randomized, open-label study for adult patients with Gaucher
disease type 1, designed to compare eliglustat tartrate to Cerezyme. Adult patients who have
previously received enzyme replacement therapy for at least three years and have reached their
therapeutic goals may qualify for this trial. The second trial, ENGAGE, is a randomized, double-blind,
placebo-controlled study for patients with a confirmed diagnosis of Gaucher disease type 1. Patients
who have not received enzyme replacement therapy within 9 months or substrate reduction therapy
within 6 months of participation may qualify for this study. Genzyme recently launched a third trial,
known as EDGE, to compare once-daily dosing of eliglustat tartrate with twice-daily dosing.
Breast Cancer Survivors Don't Need To Be Afraid Of Air Travel: U Of A Study - 21 August 2010
University of Alberta researcher Margie McNeely says results from an international study she was part
of indicates certain precautions about the risk of lymphedema for breast cancer survivors are outdated.
McNeely, from the Faculty of Rehabilitation Medicine, says women who've had breast cancer surgery
are often warned that pressure changes in an airplane cabin could trigger lymphedema, chronic swelling
in the arm. But the study she did with an Australian research team showed that only five per cent of
these women are likely at risk of developing any arm swelling when flying.
The caution about lymphedema risk is for women who have had lymph nodes removed from the
armpit, a common procedure during cancer treatment. McNeely says because these lymph nodes help
drain fluid when they are removed there is the potential for chronic swelling.
McNeely teamed up with Australian researcher Sharon Kilbreath to study the effect of air travel on 60
Canadian breast cancer survivors who were flying to Australia for an International Dragon Boat
Festival. Seventeen of these women were from Edmonton. The study also involved a group of 12
women who were travelling to the festival from different areas of Australia.
The researchers compared both of the participants' arms, the arm where lymph nodes were removed
from the armpit and the opposite unaffected arm, with a device that can detect subtle changes in fluid
difference between the arms. The measurements were done in Canada before they left and again in
Australia when they arrived.
Findings indicate that 95 per cent of the women had no arm swelling. Four women had a slight increase
but at a follow-up test, done six weeks after the women returned to Canada, three were back to
normal and only one woman was found at possible risk for chronic swelling.
McNeely says that, until now, information about air travel and lymphedema risk has not been based on
solid evidence, but says this research shows that while there is a risk of developing lymphedema during
flight, that risk is very low.
McNeely's research was published in the journal Breast Cancer Research and Treatment.
August 27, 2010 - Shire Announces European Approval Of VPRIV(R) (velaglucerase Alfa) For The
Treatment Of Type 1 Gaucher Disease –
Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company,
announced that the European Commission has granted marketing authorisation for VPRIV(R)
(velaglucerase alfa), a human cell line derived enzyme replacement therapy (ERT) for the long-term
treatment of type 1 Gaucher disease. VPRIV has been authorized as an orphan medicine through the
Centralised Procedure, making it available in 30 countries across Europe.
This approval was based on data from Shire's velaglucerase alfa clinical development programme
which represents the largest and most comprehensive clinical data set supporting registration for an
ERT for type 1 Gaucher disease. In total, over 100 Gaucher patients at 24 sites in 10 countries around
the world participated in the clinical studies, all of which met their primary endpoints.
"Gaucher disease is a rare and often debilitating condition," said Professor Tim Cox from the
Department of Medicine, University of Cambridge, and founder of the largest U.K. Gaucher clinic at
Addenbrooke's Hospital. "The European approval of VPRIV is important in that we now have an
alternative, licensed therapeutic enzyme. For type 1 patients the availability of VPRIV provides further
opportunities to individualise treatment options for this complex disorder."
Across Europe, hundreds of type 1 Gaucher patients have been receiving velaglucerase alfa through
early access programmes, developed in partnership with national authorities, Gaucher expert physicians
and patient associations. Globally there are over 850 patients on velaglucerase alfa and demand
continues to be strong. As a result, Shire has implemented a program to carefully monitor demand and
manage requests from physicians and patients in order to ensure long-term, uninterrupted treatment
with VPRIV.
"The Marketing Authorisation for VPRIV in the EU is an important milestone for Shire," said Sylvie
Gregoire, President, Shire Human Genetic Therapies. "Our efforts to accelerate our manufacturing,
clinical and regulatory timelines have resulted in VPRIV's approval in Europe and the US months ahead
of schedule."
Important Safety Information
The most serious adverse reactions in patients treated 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. Other commonly observed
adverse reactions in >10% of patients were: abdominal pain, back pain, joint pain, upper respiratory
tract infection, and activated partial thromboplastin time prolonged. Adverse reactions more commonly
seen in paediatric patients (>10% difference) included upper respiratory tract infection, rash, activated
partial thromboplastin time prolonged, and pyrexia. In clinical trials one patient developed neutralizing
antibodies.
September 1, 2010 - BioMarin Receives Orphan Drug Designation From The FDA For BMN-701
For The Treatment Of Pompe Disease -
BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) announced that it has received orphan drug
designation from the U.S. Food and Drug Administration (FDA) for BMN-701, a novel fusion of
insulin-like growth factor 2 and alpha glucosidase (IGF2-GAA) in development for the treatment of
Pompe disease. An investigational new drug application (IND) for BMN-701 has been submitted,
investigational material has been manufactured and a Phase I/II study is expected to start in the first
quarter of 2011.
"Receiving orphan drug designation from the FDA for BMN-701 is a significant milestone for our
Pompe program. As part of their assessment for designation, the FDA determined that BMN-701 is
sufficiently different from alglusidase alfa (Myozyme/Lumizyme) to allow for a unique orphan
designation. For this reason, clinical superiority over alglusidase alfa will not be necessary to secure
orphan exclusivity for BMN-701," said Jean-Jacques Bienaime, Chief Executive Officer of BioMarin.
"This emphasizes our mission of developing innovative, products for orphan diseases with an unmet
medical need. We believe BMN-701 has the potential to possibly deliver more enzyme to lysosomes
compared to traditional mannose-6-phosphate targeted approaches using the recently acquired GILT
technology."
About Pompe Disease
Pompe disease, a lysosomal storage disorder, is a progressive degenerative disease of the heart
muscle, diaphragm and skeletal muscle. It is caused by a deficiency in the lysosomal enzyme acid alpha
glucosidase which leads to the accumulation of glycogen in myocyte lysosomes and results in cell death.
The incidence is one in 40,000 births. There are two main forms of Pompe disease: adult onset with an
incidence of one in 57,000 births and infantile onset with an incidence of one in 138,000 births. The
current standard of care is Genzyme's Myozyme and Lumizyme. Prognosis with standard of care is
stabilization of the disease or minor improvements for the majority of adult onset patients.
About BioMarin
BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical
conditions. The company's product portfolio comprises four approved products and multiple clinical
and pre-clinical product candidates. Approved products include Naglazyme® (galsulfase) for
mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin;
Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed
through a 50/50 joint venture with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride)
Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck
KGaA of Darmstadt, Germany; and Firdapse™ (amifampridine phosphate), which has been approved
by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS).
Other product candidates include GALNS (N-acetylgalactosamine 6-sulfatase), which is currently in
clinical development for the treatment of MPS IVA and PEG-PAL (PEGylated recombinant
phenylalanine ammonia lyase), which is currently in Phase II clinical development for the treatment of
PKU.