ENews Vol 1 No 17
May 2009
Welcome to the National
Information Centre for Metabolic Diseases
Research News Sheet - Vol 1 No 16.
The contents of this news sheet
has been gathered from around the globe during our
research to update our information on metabolic
diseases. The contents are general and not specific to
our vision.
Amicus Therapeutics Presents Positive
Results From Phase 2 Extension Study of Amigal(TM) for Fabry
Disease at ACMG 2009 Annual Meeting --Data provide support for
expected Phase 3 program
CRANBURY, N.J., March 28, 2009 /PRNewswire-FirstCall via
COMTEX News Network/ -- Amicus Therapeutics (Nasdaq: FOLD)
announced today positive results from its ongoing Phase 2
extension study of its investigational drug, Amigal(TM) (migalastat
HCL) for Fabry disease. The results will be presented at the
American College of Medical Genetics (ACMG) 2009 Annual Meeting
in Tampa, FL.
Phase 2 Extension Study Overview:
Twenty-six subjects completed either 12 or 24 weeks of
treatment during Phase 2 studies. Twenty-three of the 26
subjects continue to receive treatment in an ongoing extension
study designed to evaluate the long term safety and efficacy of
Amigal. Ten of the 23 subjects have been on treatment for at
least 2 years and 4 subjects have been on treatment for more
than 3 years.
Preliminary Results:
Treatment with Amigal was generally well-tolerated, with no
drug-related serious adverse events. The most common adverse
events were headache, arthralgia and diarrhea.
Subjects identified as responders to Amigal at the completion
of the Phase 2 studies continued to maintain elevated levels of
the target enzyme (a-Gal A), as measured in white blood cells,
and reduced levels of the target substrate (kidney GL-3), as
measured in urine.
A reduction of GL-3 levels was also observed in interstitial
capillary cells from kidney biopsies. Previously reported Phase
2 results indicated that little to no GL-3 was detected in these
cells in most subjects prior to treatment with Amigal. The new
data were obtained from the retesting of biopsies using an
improved methodology. Preliminary results from the evaluation of
modified doses and a new dosing regimen were also presented.
Derralynn Hughes, MA, DPhil, MRCPath, Senior Lecturer in the
Haematology Department Academic Haematology, Royal Free &
University College Medical School, London, UK, stated, "The data
with migalastat continue to be encouraging. I believe migalastat
has the potential to be an important new treatment option for
Fabry patients."
John F. Crowley, President and CEO of Amicus Therapeutics,
added, "We are very pleased with this additional set of Phase 2
data and are very confident we have a solid basis for a
successful Phase 3 program. We continue to work in collaboration
with the FDA and remain on track to finalize our protocol and
initiate the Phase 3 program in the second quarter of this
year."
In January 2009, Amicus announced that the FDA supports a
Phase 3 clinical trial comparing Amigal to placebo based on a
surrogate primary endpoint of the change in the amount of kidney
GL-3, the substrate that accumulates in the cells of Fabry
patients. The Company expects to finalize the protocol and
initiate Phase 3 development in the second quarter of this year.
Amicus is developing Amigal as part of a strategic
collaboration with Shire Human Genetic Therapies (HGT), a
business unit of Shire plc, to develop and commercialize Amicus'
three lead pharmacological chaperone compounds for lysosomal
storage disorders. Under the agreement, Shire received
commercial rights outside of the United States. Amicus retains
all U.S. rights.
About Fabry Disease
Fabry disease is a lysosomal storage disorder caused by
inherited genetic mutations in the GLA gene, which result in
deficient activity of the enzyme alpha-galactosidase A (a-Gal
A). Deficient a-Gal A activity leads to lysosomal accumulation
of globotriaosylceramide (GL-3), which is believed to cause the
various symptoms of Fabry disease, including pain, kidney
failure and increased risk of heart attack and stroke. Amigal is
designed to selectively bind to and stabilize a-Gal A, which
facilitates proper trafficking of the enzyme to the lysosomes,
where it is needed to break down GL-3.
Fabry disease is estimated to affect approximately 5,000 to
10,000 people in the developed world, but recent evidence
suggests that the disease may be significantly under-diagnosed.
The U.S. Food and Drug Administration's Office of Orphan
Products Development has granted orphan designation for Amigal
in the United States, and the European Commission has designated
Amigal as an orphan medicinal product in the European Union.
About Shire plc
Shire's strategic goal is to become the leading specialty
biopharmaceutical company that focuses on meeting the needs of
the specialist physician. Shire focuses its business on
attention deficit and hyperactivity disorder (ADHD), human
genetic therapies (HGT) and gastrointestinal (GI) diseases as
well as opportunities in other therapeutic areas to the extent
they arise through acquisitions. Shire's in-licensing, merger
and acquisition efforts are focused on products in specialist
markets with strong intellectual property protection and global
rights. Shire believes that a carefully selected and balanced
portfolio of products with strategically aligned and relatively
small-scale sales forces will deliver strong results.
For further information on Shire, please visit the Company's
website:
www.shire.com.
About Amicus Therapeutics
Amicus Therapeutics is a biopharmaceutical company developing
novel, oral therapeutics known as pharmacological chaperones for
the treatment of a range of human genetic diseases.
Pharmacological chaperone technology involves the use of small
molecules that selectively bind to and stabilize proteins in
cells, leading to improved protein folding and trafficking, and
increased activity. Amicus is initially targeting lysosomal
storage disorders, which are severe, chronic genetic diseases
with unmet medical needs.
Forward-Looking Statements
This press release contains "forward-looking statements"
within the meaning of the Private Securities Litigation Reform
Act of 1995. Words such as, but not limited to, "look forward
to," "believe," "expect," "anticipate," "estimate," "intend,"
"plan," "targets," "likely," "will," "would," "should" and
"could," and similar expressions or words identify
forward-looking statements. Such forward-looking statements are
based upon current expectations that involve risks, changes in
circumstances, assumptions and uncertainties. The inclusion of
forward-looking statements should not be regarded as a
representation by Amicus that any of its plans will be achieved.
Any or all of the forward-looking statements in this press
release may turn out to be wrong. They can be affected by
inaccurate assumptions Amicus might make or by known or unknown
risks and uncertainties. For example, with respect to statements
regarding the goals, progress, timing and outcomes of ongoing
discussions with regulatory authorities and the potential goals,
progress, timing and results of clinical trials, actual results
may differ materially from those set forth in this release due
to the risks and uncertainties inherent in the business of
Amicus, including, without limitation: the potential inability
to reach final agreement with regulatory agencies on the use of
a surrogate endpoint and phase 3 trial design for Amigal, the
potential that the interim results of the phase 2 extension
study may not be predictive of the final results of the study,
the potential that results of clinical or pre-clinical studies
indicate that the product candidates are unsafe or ineffective;
and, our dependence on third parties in the conduct of our
clinical studies. Further, the results of earlier clinical
trials may not be predictive of future results. Additionally,
all forward looking statements are subject to other risks
detailed in our Annual Report on Form 10-K for the year ended
December 31, 2008, and our other public filings with the
Securities and Exchange Commission. You are cautioned not to
place undue reliance on these forward-looking statements, which
speak only as of the date hereof. All forward-looking statements
are qualified in their entirety by this cautionary statement,
and Amicus undertakes no obligation to revise or update this
news release to reflect events or circumstances after the date
hereof. This caution is made under the safe harbor provisions of
Section 21E of the Private Securities Litigation Reform Act of
1995.
FOLD-G
SOURCE Amicus Therapeutics
http://www.amicustherapeutics.com/
BioMarin's Clinical Trial Application for
GALNS for Morquio A Syndrome Accepted by the MHRA
NOVATO, Calif., March 18 /PRNewswire-FirstCall/ -- BioMarin
Pharmaceutical Inc. (Nasdaq: BMRN) announced today that its
application for clinical trial authorization (CTA) for BMN 110
or N-acetylgalactosamine 6-sulfatase (GALNS), intended for the
treatment of the lysosomal storage disorder
Mucopolysaccharidosis Type IVA (MPS IVA), or Morquio A Syndrome,
has been accepted by the United Kingdom Medicines and Healthcare
Products Regulatory Agency (MHRA). BioMarin expects to initiate
a Phase 1/2 clinical trial in the next few weeks.
"There are a significant number of untreated Morquio patients
in clinics around the world who are very anxious to receive a
new treatment option. We are moving forward expeditiously with
our GALNS program in the hope of bringing those patients the
much-needed treatment they deserve. BioMarin has successfully
advanced two enzyme replacement therapies from IND filing to FDA
approval in approximately five years each and we plan to
leverage our clinical, manufacturing and regulatory expertise to
develop this treatment for Morquio A syndrome," said
Jean-Jacques Bienaime, Chief Executive Officer of BioMarin.
"Enrollment in the MorCAP study initiated last November is
continuing and we continue to add additional sites. We expect
that this survey study will yield valuable information on
Morquio patients and will aid in our scientific understanding of
the disorder as we further pursue this program."
The Phase 1/2 study is designed as an open-label,
within-patient dose escalation trial in approximately 20
patients followed by a treatment continuation phase. During the
dose escalation phase of the study, subjects will receive weekly
intravenous infusions of BMN 110 in 3 consecutive 12-week dosing
intervals. The objectives of the Phase 1/2 study will be to
evaluate safety, pharmacokinetics, pharacodynamics and to
identify the optimal dose of GALNS for future studies.
BioMarin has developed and manufactures two FDA-approved
enzyme replacement therapies, one for the treatment of MPS I and
one for the treatment of MPS VI. Naglazyme(R) (galsulfase) for
MPS VI is wholly developed and commercialized by BioMarin.
Aldurazyme(R) (laronidase) for MPS I is manufactured by BioMarin
and marketed by Genzyme Corporation.
About MPS IVA
Mucopolysaccharidosis IVA (MPS IVA, also known as Morquio A
Syndrome) is a disorder characterized by deficient activity of
N-acetylgalactosamine 6-sulfatase (GALNS) causing excessive
lysosomal storage of keratan sulfate (KS). This excessive
storage causes a systemic skeletal dysplasia, short stature, and
joint abnormalities, which limit mobility and endurance.
Malformation of the thorax as well as macrophage dysfunction in
the lung likely impairs respiratory function and contributes to
sinopulmonary infections. Odontoid dysplasia and ligamentous
laxity can commonly cause cervical spinal instability and
potentially spinal cord compression. Other symptoms may include
recurrent infections, hearing loss, corneal clouding, and heart
valvular disease. Initial symptoms often become evident in the
first five years of life. Depending on severity of the disorder,
age of diagnosis will vary. Many patients become wheelchair
dependent in their second decade of life and undergo numerous
surgeries to alleviate life-threatening conditions caused by the
underlying enzyme deficiency.
The incidence estimates for MPS IVA vary widely, between 1 in
200,000 live births to 1 in 300,000 live births. Approximately
400 patients worldwide have been identified and tracked through
an independent registry. Based on the number of identified
patients to date, the prevalence of patients with MPS IVA
appears similar to that with MPS I.
About BioMarin
BioMarin develops and commercializes innovative
biopharmaceuticals for serious diseases and medical conditions.
The company's product portfolio comprises three approved
products and multiple clinical and preclinical product
candidates. Approved products include Naglazyme(R) (galsulfase)
for mucopolysaccharidosis VI (MPS VI), a product wholly
developed and commercialized by BioMarin; Aldurazyme(R) (laronidase)
for mucopolysaccharidosis I (MPS I), a product which was
developed through a 50/50 joint venture with Genzyme
Corporation; and Kuvan(R) (sapropterin dihydrochloride) Tablets,
a product for the treatment of phenylketonuria (PKU), developed
in partnership with Merck Serono, a division of Merck KGaA of
Darmstadt, Germany. Other product candidates include PEG-PAL (PEGylated
recombinant phenylalanine ammonia lyase), which is currently in
Phase 1 clinical development for the treatment of PKU. For
additional information, please visit
www.BMRN.com.
Information on BioMarin's website is not incorporated by
reference into this press release.
Forward-Looking Statement
This press release contains forward-looking statements about
the business prospects of BioMarin Pharmaceutical Inc.,
including, without limitation, statements about: the development
of its program for MPS IVA, and particularly the timing and
conuct of clinical trials related thereto, and expectations
regarding filings with regulatory agencies. These
forward-looking statements are predictions and involve risks and
uncertainties such that actual results may differ materially
from these statements. These risks and uncertainties include,
among others: the results of current and planned pre-clinical
trials related to the enzyme replacement therapy for MPS IVA;
the content and timing of decisions by the U.S. Food and Drug
Administration, EMEA and other regulatory agencies, particularly
with respect to the enzyme replacement therapy for MPS IVA, and
those factors detailed in BioMarin's filings with the Securities
and Exchange Commission, including, without limitation, the
factors contained under the caption "Risk Factors" in BioMarin's
2008 Annual Report on Form 10-K. Stockholders are urged not to
place undue reliance on forward-looking statements, which speak
only as of the date hereof. BioMarin is under no obligation, and
expressly disclaims any obligation to update or alter any
forward-looking statement, whether as a result of new
information, future events or otherwise.
BioMarin(R), Naglazyme(R) and Kuvan(R) are registered
trademarks of BioMarin Pharmaceutical Inc.
Aldurazyme(R) is a registered trademark of BioMarin/Genzyme
LLC.
SOURCE BioMarin Pharmaceutical Inc. -0- 03/18/2009
CONTACT:
Investors, Eugenia Shen, +1-415-506-6570, or
Media, Susan Berg, +1-415-506-6594,
both of BioMarin Pharmaceutical Inc.
http://www.bmrn.com
FDA Grants Priority Review of a
Supplemental Biologics License Application for Cinryze(TM) C1
Inhibitor (Human) as Treatment for Acute Attacks of Hereditary
Angioedema (HAE)
- PDUFA Date for Cinryze for Acute HAE Indication is June 3,
2009 -
EXTON, Pa., Feb. 3 /PRNewswire-FirstCall/ -- ViroPharma
Incorporated (Nasdaq: VPHM) today announced that the U.S. Food
and Drug Administration (FDA) has granted priority review for
Cinryze C1 Inhibitor (human) as a treatment for acute attacks of
Hereditary Angioedema (HAE). The supplemental Biologics License
Application (sBLA), submitted to the FDA on December 1, 2008,
was based on a re-analysis and resubmission of data from a
pivotal Phase 3 acute treatment study of Cinryze and interim
data from an ongoing open label acute study of the drug.
Cinryze was approved on October 10, 2008 for routine
prophylaxis against angioedema attacks in adolescent and adult
patients with HAE.
Priority review is granted by the FDA for a treatment that
addresses an unmet medical need and demonstrates improvement
over existing therapies. The FDA expedites the approval process
for applications granted priority review from ten to six months.
The PDUFA date for the sBLA is June 3, 2009.
"The priority review designation marks a positive step in
bringing another use of Cinryze closer to the patients who
suffer acute attacks of hereditary angioedema," commented
Vincent Milano, ViroPharma's president and chief executive
officer. "We look forward to working with the FDA on approval so
that we can help this additional group of patients."
The administration of Cinryze produced beneficial effects in
treating acute HAE attacks in these studies. The safety profile
was similar to that observed with the use of Cinryze for routine
prophylaxis of angioedema attacks in patients with HAE, the
currently approved indication. Overall, more than 9,000 doses of
Cinryze have been administered to over 180 patients in all
controlled and open label clinical studies of Cinryze for both
acute treatment and routine prophylaxis against angioedema
attacks.
The Phase 3 acute treatment study was a randomized, double
blind, placebo controlled multi-center trial in 71 patients
evaluating the safety and efficacy profile of Cinryze for
treatment of HAE attacks. The primary efficacy measure in the
pivotal Phase 3 acute treatment study was the time from initial
treatment to the start of unequivocal relief of the defining
symptom. Based on the primary efficacy variable, in the All
Randomized (ITT) Dataset, the likelihood of a patient having the
start of unequivocal relief of the defining symptom was 2.048
times greater in the Cinryze treatment group than in the placebo
treatment group (p=0.048). The median time to the start of
unequivocal relief of the defining symptom was shorter in
subjects in the Cinryze treatment group (two hours) than in
subjects in the placebo treatment group (greater than four
hours).
In the open label study of Cinryze as treatment for acute
attacks of HAE, no patients who had acute laryngeal edema
attacks required hospitalization or intubation. Cinryze was
generally well tolerated. There were no deaths or serious
adverse reactions related to Cinryze administration, or
discontinuations due to treatment-emergent adverse events. In
the analysis of 447 acute attacks in 82 patients, open label
Cinryze administration provided substantial relief of the
defining symptom in 93.4 percent of the attacks within four
hours of injection, with a median time to onset of relief of 30
minutes. There was no observed loss of effectiveness over
multiple administrations of Cinryze for subsequent HAE attacks.
About Cinryze C1 Inhibitor (human)
Cinryze is a highly purified, pasteurized and nanofiltered
plasma-derived C1 inhibitor product that has been approved by
FDA for routine prophylaxis against angioedema attacks in
adolescent and adult patients with HAE. C1 inhibitor therapy has
been used acutely for more than 35 years in Europe to treat
patients with C1 inhibitor deficiency. Cinryze has not been
approved for acute treatment in the United States or any other
jurisdiction.
Cinryze has been generally well tolerated. The most common
adverse reactions observed have been upper respiratory
infection, sinusitis, rash and headache. No drug-related serious
adverse events (SAEs) have been observed in clinical trials.
Severe hypersensitivity reactions may occur. Thrombotic events
have occurred in patients receiving high dose off-label C1
inhibitor therapy well above the approved treatment dosage
regimen. With any blood or plasma derived product, there may be
a risk of transmission of infectious agents, e.g. viruses and,
theoretically, the CJD agent. The risk has been reduced by
screening patients for prior exposure to certain virus
infections and by manufacturing steps to reduce the risk of
viral transmission including pasteurization and nanofiltration.
Cinryze is for intravenous use only. A dose of 1000 Units of
Cinryze can be administered every 3 or 4 days for routine
prophylaxis against angioedema attacks in HAE patients. Cinryze
is administered at an injection rate of 1 mL per minute.
About Hereditary Angioedema
HAE is a rare, severely debilitating, life-threatening
genetic disorder caused by a deficiency of C1 inhibitor, a human
plasma protein. This condition is the result of a defect in the
gene controlling the synthesis of C1 inhibitor. C1 inhibitor
maintains the natural regulation of the contact, complement, and
fibrinolytic systems, that when left unrestricted, can initiate
or perpetuate an attack by consuming the already low levels of
endogenous C1 inhibitor in HAE patients. Patients with C1
inhibitor deficiency experience recurrent, unpredictable,
debilitating, and potentially life threatening attacks of
inflammation affecting the larynx, abdomen, face, extremities
and urogenital tract. Patients with HAE experience approximately
20 to 100 days of incapacitation per year. There are estimated
to be at least 4600 people with HAE in the United States.
For more information on HAE, visit the U.S. HAE Association's
website at:
www.haea.org.
About ViroPharma Incorporated
ViroPharma Incorporated is a biopharmaceutical company
dedicated to the development and commercialization of products
that address serious diseases treated by physician specialists
and in hospital settings. ViroPharma commercializes Vancocin(R)
(vancomycin hydrochloride capsules, USP), approved for oral
administration for treatment of antibiotic-associated
pseudomembranous colitis caused by Clostridium difficile and
enterocolitis caused by Staphylococcus aureus, including
methicillin-resistant strains, and Cinryze(TM) (C1 inhibitor
(human)) for routine prophylaxis against angioedema attacks in
adolescent and adult patients with hereditary angioedema (HAE),
also known as C1 inhibitor deficiency (for prescribing
information on ViroPharma's commercial products, please download
the package inserts at
http://www.viropharma.com/Products.aspx). ViroPharma
currently focuses its drug development activities in diseases
including cytomegalovirus (CMV), HAE and C. difficile.
ViroPharma routinely posts information, including press
releases, which may be important to investors in the investor
relations and media sections of our company's web site,
www.viropharma.com.
The company encourages investors to consult these sections for
more information on ViroPharma and our business.
Forward-Looking Statements
Certain statements in this press release contain
forward-looking statements that involve a number of risks and
uncertainties. Forward-looking statements provide the Company's
current expectations or forecasts of future events.
Forward-looking statements in this press release include
statements regarding ViroPharma's clinical development programs.
Our actual results could differ materially from those results
expressed in, or implied by, these forward-looking statements.
The development and commercialization of pharmaceutical products
is subject to risks and uncertainties. The data that were
submitted to the U.S. Food and Drug Administration includes data
from two separate studies including the pivotal Phase 3 study of
Cinryze in acute HAE attacks and the ongoing open-label study of
Cinryze for acute treatment of HAE, which includes partial data
from an ongoing open label study. There can be no assurance that
the complete data from the open label study will demonstrate
that Cinryze successfully treats all types of acute hereditary
angioedema (HAE) attacks and may not be predictive of the
results of any future testing. The FDA may view the data
regarding the use of Cinryze for acute treatment of HAE we have
submitted as a supplemental BLA as insufficient or inconclusive,
not accept our submission, request additional data, require
additional clinical studies, delay any decision past the time
frames anticipated by us, limit any approved indications, deny
the approval of Cinryze for acute treatment of HAE or approve a
competing product which has been granted orphan drug designation
thereby preventing Cinryze from reaching the market for acute
treatment of HAE. These factors, and other factors, including,
but not limited to those described in ViroPharma's annual report
on Form 10-K and quarterly reports on Form 10-Q filed with the
Securities and Exchange Commission during 2008, could cause
future results to differ materially from the expectations
expressed in this press release. The forward-looking statements
contained in this press release may become outdated over time.
ViroPharma does not assume any responsibility for updating any
forward-looking statements.
SOURCE ViroPharma Incorporated - 02/03/2009
CONTACT: Investors, Robert A. Doody Jr., Assistant Director,
Investor
Relations, +1-610-321-6290,
or Media, Kristina M. Broadbelt, Assistant
Director, PR & Advocacy, +1-610-321-2358, both of ViroPharma
Incorporated.
www.viropharma.com
Hyperion Therapeutics Announces Results
for Phase II Study in Urea Cycle Disorders
Company
preparing to initiate phase III trial
South San
Francisco, California - March 30, 2009
Hyperion Therapeutics, Inc. today announced top-line results
from their phase II study of HPN-100 for the treatment of urea
cycle disorders. The data was presented on March 27th at the
16th Annual Clinical Genetics Meeting of the American College of
Medical Genetics by Brendan Lee, M.D., Ph.D., Howard Hughes
Medical Institute Investigator and Professor Department of
Molecular and Human Genetics Baylor College of Medicine. The
abstract is entitled “Phase 2 Study of A Novel Ammonia
Scavenging Agent In Adults With Urea Cycle Disorders (UCDs).”
The phase II study was an open-label, fixed sequence,
switch-over study [BUPHENYL® (sodium phenylbutyrate) to HPN-100]
of ten adult subjects with UCDs. The primary endpoint was
safety; secondary outcome measures included pharmacokinetics (PK),
pharmacodynamics (PD), and exploratory efficacy as measured by
time-normalized area under the curve (TNAUC) for ammonia.
Patients were enrolled on their stable dose of BUPHENYL and
24-hour PK, ammonia measurements, amino acids, and urine
collections were completed in a study unit after seven days of
on-study treatment. Each patient was then switched to HPN-100 at
a dose providing the same amount of the active ingredient (PBA).
After seven days of HPN-100 dosing, patients were re-admitted
for the same battery of assessments that were completed at day
seven. Both BUPHENYL and HPN-100 were administered TID with
meals.
Twenty-one adverse events (AEs) occurred in seven subjects
during BUPHENYL treatment and fifteen AEs occurred in five
subjects with HPN-100. There were two SAEs related to
hyperammonemia; both occurred during 100% BUPHENYL treatment. No
SAEs occurred during 100% HPN-100 treatment. Ammonia values were
~30% lower on HPN-100 assessed as TNAUC over 24 hours [mean (SD)
= 38.4 (19.6) versus 26.1 (10.3) umol/L), Cmax = 79.1 (40.1)
versus 56.3 (27.9) umol/L, or the percentage of normal values:
58% vs. 72%]. Differences in ammonia values were not
statistically significant.
"We are very pleased with the study results and our recent
end of phase II meeting with the Food and Drug Administration,”
said Don Santel, Chief Executive Officer of Hyperion
Therapeutics. “We are currently finalizing our phase III study
protocol in consultation with the Agency and are eager to
further explore the potential of HPN-100 for the treatment of
urea cycle disorders."
About Urea Cycle Disorders
Urea cycle disorders are inherited, inborn errors of
metabolism present in an estimated 1 in 10,000 births in the
United States. Patients with urea cycle disorders are deficient
in one of the key enzymes that comprise the urea cycle, the
body’s primary vehicle for removing ammonia, a potent
neurotoxin, from the bloodstream. Onset may occur at any age
depending on the severity of the disorder. Left untreated, urea
cycle disorders can cause dangerously heightened levels of
ammonia in the bloodstream (hyperammonemia) resulting in brain
damage, coma, and/or death.
About HPN-100
HPN-100 is a pro-drug of phenylbutyrate and a pre-pro-drug of
phenylacetic acid, the active moiety of BUPHENYL®, the only
therapy currently FDA-approved as adjunctive therapy for the
chronic management of patients with the most prevalent urea
cycle deficiencies including those related to carbamylphosphate
synthetase, ornithine transcarbamylase and argininosuccinic acid
synthetase. HPN-100, which is dosed orally in liquid form,
provides an alternative pathway to the urea cycle for the
disposal of waste nitrogen through the renal excretion of
phenylacetylglutamine, which is formed from phenylacetic acid
and glutamine.
Hyperion and Ucyclyd Pharma, Inc., a subsidiary of Medicis
Pharmaceutical Corporation, entered into a collaboration
agreement for HPN-100 in August 2007. Under the terms of the
agreement, Hyperion is conducting ongoing research and
development of HPN-100 for urea cycle disorders, hepatic
encephalopathy, and other forms of hyperammonemia.
About BUPHENYL®
BUPHENYL® is indicated as adjunctive therapy in the chronic
management of patients with urea cycle disorders involving
deficiencies of carbamylphosphate synthetase (CPS), ornithine
transcarbamylase (OTC), or argininosuccinic acid synthetase
(AS). BUPHENYL® should not be administered to patients with
known hypersensitivity to sodium phenylbutyrate or any component
of this preparation. The most common adverse reactions
associated with BUPHENYL® were amenorrhea dysfunction, decreased
appetite, body odor (probably caused by its metabolite
phenylacetate) and bad taste or taste aversion. Patients with
urea cycle disorders should not take valproic acid, haloperidol,
or steroids as these drugs have been reported to increase blood
ammonia levels, and probenecid may affect the kidneys’
excretion. Use with great care, if at all, in patients with
congestive heart failure or severe renal insufficiency, and in
clinical states where there is sodium retention with edema. Use
caution when administering to patients with hepatic or renal
insufficiency or inborn errors of beta oxidation. The safety or
efficacy of doses in excess of 20 grams (40 tablets) per day has
not been established.
About Hyperion Therapeutics
Hyperion Therapeutics is a privately held specialty
therapeutics company focused on the development of therapies
that address critical unmet needs and underserved patient
populations in the areas of gastroenterology and hepatology.
Hyperion is headquartered in South San Francisco, CA. For
additional information, visit www.hyperiontx.com.
BUPHENYL® is exclusively licensed from Ucyclyd Pharma, Inc.
BUPHENYL® is a registered trademark of Ucyclyd Pharma, Inc.
Full Prescribing Information for BUPHENYL® is available at
www.Buphenyl.com or by
contacting Ucyclyd Pharma, Inc.
Press
contact:
Christine Nash
Hyperion Therapeutics, Inc.
650-745-7844
Zavesca®
(miglustat) receives EU approval for the treatment of
progressive neurological manifestations in patients with
Niemann-Pick type C disease
ALLSCHWIL/BASEL, SWITZERLAND - 29 January 2009 -
Actelion Ltd
(SIX: ATLN) announced today that Zavesca® (miglustat) has been
approved in the European Union for the treatment of progressive
neurological manifestations in adult patients and pediatric
patients with Niemann-Pick type C disease (NPC). Zavesca® is the
first treatment to be approved for patients with Niemann-Pick
type C disease, a very rare, invariably progressive and
eventually fatal neurodegenerative genetic disorder affecting
both children and adults.
Zavesca® (100 mg miglustat) is already indicated for the oral
treatment of adult patients with mild to moderate type 1 Gaucher
disease. Zavesca® may only be used in the treatment of type 1
Gaucher patients for whom enzyme replacement therapy is
unsuitable.
Jean-Paul Clozel, M.D. and Chief Executive Officer of
Actelion commented: "I am very proud that Actelion - together
with the scientific community - has been able to demonstrate the
role of Zavesca® in reducing the progression of clinically
relevant neurological symptoms in patients with NPC. I would
like to thank both the patients and their families who, over the
years, have been involved in our clinical program with so much
dedication, as well as all the clinical experts for their
continuous support. Actelion will continue to support the rare
disease community in its efforts to advance science and medicine
for the patient".
Ed Wraith, M.D., Royal Manchester Children's Hospital,
commented: "For the first time we have an approved therapy for
NPC. The data on the effects of treatment with Zavesca® obtained
in a clinical trial and in a retrospective cohort study
consistently showed a favorable clinical response. As a treating
physician I am acutely aware of the importance of reducing
progression of neurological symptoms."
Regulatory proceedings to extend the use of miglustat in
patients with NPC are ongoing in other territories worldwide.
About Niemann-Pick type C disease
NPC is a very rare, fatal, neurodegenerative, genetic
condition, primarily affecting children and teenagers but which
can strike at any age. The symptoms are caused by the storage of
some glycosphingolipids within certain cells in the body,
including the brain. It is invariably progressive and most
patients die within five to ten years of diagnosis; for the
majority the disease is fatal during childhood. Neurological
deterioration is the key feature of the disease, and can
manifest itself as clumsy body movements, balance problems, slow
and slurred speech, difficulty in swallowing, problems with eye
movements and seizures. Intellectual decline is also common. In
the final stages of the disease the child or young adult is
frequently bedridden, has little muscle control and is
intellectually impaired. Diagnosis of the disease can be
difficult and lengthy due to its rarity and heterogeneity. There
is currently no treatment option approved for this condition.
###
Notes to the editor
About Zavesca® and Niemann-Pick type C disease
Zavesca® is indicated for the treatment of progressive
neurological manifestations in adult patients and pediatric
patients with Niemann-Pick type C disease.
In order to gain approval for Zavesca® in Niemann-Pick type C
disease, a set of clinical data were obtained from one clinical
trial OGT918-007 and two multicenter retrospective cohort
studies in patients with NPC.
The usual dose of Zavesca® in adult NPC patients was 200 mg
miglustat three times a day, and was adjusted according to body
surface area in pediatric NPC patients.
In the clinical trial OGT918-007, adult and juvenile patients
with NPC (n=29, age >=12 years) were randomized to either
miglustat 200 mg t.i.d. (n=20) or standard of care (n=9) for 12
months [1]. In addition, 12 children aged 4-12 years received
miglustat at a dose adjusted for body surface area. All patients
were then given miglustat for another 12 months. Horizontal
saccadic eye movement (HSEM) velocity was the primary endpoint.
Other endpoints included swallowing, ambulation, neurological
examination, neuropsychological assessment, tremor and quality
of life. At 12 months, HSEM velocity had improved in patients
treated with miglustat versus those receiving standard care;
results were significant when patients taking benzodiazepines
were excluded (p=0.028) [1]. Children showed an improvement in
HSEM velocity of similar size at 12 months. Improvement in
swallowing capacity, stable auditory acuity, and a slower
deterioration in ambulatory index were also seen in treated
patients older than 12 years [1].
In an uncontrolled extension phase of the OGT918-007 trial,
data indicated that treatment with miglustat can provide disease
stabilization for important markers of neurological dysfunction
in NPC disease, both in the juvenile/adult and pediatric
cohorts, further strengthening the interpretation of a treatment
effect of miglustat observed at 12 months in the controlled
phase of the trial [2,3].
The safety and tolerability of miglustat 200 mg three times a
day in clinical trial participants was consistent with previous
trials in type 1 Gaucher disease, where half this dose was used
[1, 2, 3].
A first retrospective cohort study was performed in 25
centers in 12 countries to assess data on changes of
neurological status and overall utility of treatment with
miglustat in 66 NPC patients receiving miglustat outside of the
clinical trial OGT918-007 for a mean duration of 1.5 years. A
disease-specific disability scale was used to evaluate the
severity of dysphagia (swallowing), dystonia (manipulation),
ataxia (ambulation) and dysarthria (language articulation) at
diagnosis, treatment initiation and last visit [4]. A majority
of patients remained at least stable after treatment with regard
to the four parameters, indicating that miglustat provides
clinically relevant benefits on neurological disease progression
in patients with NPC [4].
A second retrospective cohort study was performed in 7
centers in 6 countries to assess data on changes in neurological
status in 57 patients not treated with miglustat during the
natural course of the disease for a mean duration of 5.5 years.
The same disease-specific disability scale was used to evaluate
the severity of dysphagia, dystonia, ataxia and dysarthria at
the time of diagnosis until the last visit. The results will be
presented in the first half of 2009.
The benefit of treatment with Zavesca® for neurological
manifestations in patients with Niemann-Pick type C disease
should be evaluated on a regular basis, e.g. every 6 months;
continuation of therapy should be re-appraised after at least 1
year of treatment with Zavesca®.
About Zavesca® and type 1 Gaucher disease
Zavesca® (100 mg miglustat capsule) is indicated for the oral
treatment of adult patients with mild to moderate type 1 Gaucher
disease. Zavesca® may only be used in the treatment of type 1
Gaucher patients for whom enzyme replacement therapy is
unsuitable. It is approved in the European Union, the United
States, Canada, Switzerland, Brazil, Australia, Turkey and
Israel.
Zavesca® safety information
Gastrointestinal events, mainly diarrhea, have been observed
in more than 80% of patients treated with Zavesca®, either at
the onset of treatment or intermittently during treatment. The
majority of cases are mild and are expected to resolve after the
first weeks on therapy. In clinical practice, diarrhea has been
observed to respond to diet modification (reduction of lactose
and other carbohydrate intake), to taking Zavesca® away from
meals, and/or to antidiarrheal medicinal products such as
loperamide. In some patients, temporary dose reduction may be
necessary. Patients with chronic diarrhea or other persistent
gastrointestinal events that do not respond to these
interventions should be investigated according to clinical
practice. Zavesca® has not been evaluated in patients with a
history of significant gastrointestinal disease, including
inflammatory bowel disease.
Cases of peripheral neuropathy have been reported in patients
treated with Zavesca®. Peripheral neuropathy seems to be more
common in patients with type 1 Gaucher disease compared to the
general population. All patients should undergo baseline and
repeat neurological evaluation. Patients who develop symptoms
such as numbness and tingling should have a careful
re-assessment of risk benefit.
Zavesca® may cause fetal harm if administered to a pregnant
woman and is contraindicated in women who are or who may become
pregnant; patients should be informed of the potential hazard to
the fetus. There is a risk of impaired fertility in men. Men
should maintain reliable contraceptive methods and not plan to
conceive while taking Zavesca® and for three months thereafter.
Reduced growth has been reported in some pediatric patients
with Niemann-Pick type C disease in the early phase of treatment
with Zavesca® where the initial reduced weight gain may be
accompanied or followed by reduced height gain. Growth should be
monitored in pediatric and adolescent patients during treatment
with Zavesca®; the benefit/risk balance should be re-assessed on
an individual basis for continuation of therapy.
Mild reductions in platelet counts without association to
bleeding were observed in some patients with Niemann-Pick type C
disease treated with Zavesca®. In patients included in the
clinical trial, 40%-50% of patients had platelet counts below
the lower limit of normal at baseline. Monitoring of platelet
counts is recommended in these patients.
References
1. Patterson MC, Vecchio D, Prady H, Abel L and Wraith
JE. Miglustat for treatment of Niemann-Pick C disease: a
randomised controlled study. Lancet Neurol 2007; 6:765-772.
2. Patterson MC, Vecchio D, Prady H, Abel L and Wraith
JE. Miglustat for treatment of Niemann-Pick C disease: results
of 24 month's treatment. Proceedings of 57th Annual meeting of
the American Society of Human Genetics, 2007; abstract # 2253.
3. Patterson MC, Vecchio D, Jacklin E and Wraith JE.
Miglustat in Niemann-Pick disease Type C (NPC): long-term data
from a clinical trial. Proceedings of 58th Annual meeting of the
American Society of Human Genetics, 2008; abstract # 766.
4. Pineda M, Wraith JE, Sedel F, et al. Miglustat in
patients with Niemann-Pick type C disease (NPC): a multicentre
retrospective survey. Journal of Inherited Metabolic Disease
2008; 31(Suppl 1) 98. Note: this abstract describes the results
of the survey with the first 44 cases collected.
Actelion Ltd
Actelion Ltd is a biopharmaceutical company with its
corporate headquarters in Allschwil/Basel, Switzerland.
Actelion's first drug Tracleer®, an orally available dual
endothelin receptor antagonist, has been approved as a therapy
for pulmonary arterial hypertension. Actelion markets Tracleer®
through its own subsidiaries in key markets worldwide, including
the United States (based in South San Francisco), the European
Union, Japan, Canada, Australia and Switzerland. Actelion,
founded in late 1997, is a leading player in innovative science
related to the endothelium - the single layer of cells
separating every blood vessel from the blood stream. Actelion's
over 1900 employees focus on the discovery, development and
marketing of innovative drugs for significant unmet medical
needs. Actelion shares are traded on the SIX Swiss Exchange
(ticker symbol: ATLN) as part of the Swiss blue-chip index SMI
(Swiss Market Index SMI® )
For further information please contact:
Roland Haefeli
Vice President, Head of Investor Relations & Public Affairs
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123
Allschwil
+41 61 565 62 62
+1 650 624 69 36
http://www.actelion.com
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