Data Presented at 59th American Academy of Neurology Annual Meeting
BOSTON and SOUTH PLAINFIELD, N.J., May 4 /PRNewswire/ -- PTC
Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the
discovery and development of small-molecule drugs targeting
post-transcriptional control processes, today announced positive interim
data from a Phase 2 clinical trial of PTC124 in patients with Duchenne
muscular dystrophy (DMD) due to a nonsense mutation. The results from the
first two cohorts of the three-cohort study show that treatment with PTC124
was associated with increases in muscle dystrophin expression and
reductions in serum creatinine kinase values in at least 50 percent of
evaluable patients. These data were presented today at the 59th American
Academy of Neurology (AAN) Annual Meeting.
(Logo: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO )
Patients with DMD lack dystrophin, a protein that is critical to the
structural stability of muscle fibers. This Phase 2 multi-site, open-label,
dose-ranging clinical trial is evaluating muscle dystrophin expression in
patients with nonsense-mutation-mediated DMD. Blood levels of
muscle-derived creatine kinase are being measured as assessments of muscle
integrity. PTC124 safety, compliance, and pharmacokinetics are also being
evaluated.
"These data provide clinical evidence that PTC124 treatment may address
the underlying cause of DMD," said Dr. Richard Finkel, Director of the
Neuromuscular Program, Children's Hospital of Philadelphia, PA, who
presented these results today at AAN as one of the trial's lead
investigators. "Development of PTC124 offers the potential for a new
therapeutic option for patients with DMD due to a nonsense mutation."
Langdon Miller, M.D., Chief Medical Officer of PTC, added, "We are very
pleased with these additional pharmacologic proof-of-concept data from our
short-term Phase 2 clinical trial of PTC124 in patients with DMD. Based on
the growing body of Phase 2 clinical data, we plan to initiate longer-term
clinical trials to evaluate the clinical benefit of PTC124 in patients with
DMD."
The Phase 2 clinical trial is being conducted at three sites in the
United States: Children's Hospital of Philadelphia, Philadelphia,
Pennsylvania; Cincinnati Children's Hospital Medical Center, Cincinnati,
Ohio; and the University of Utah, Salt Lake City, Utah. In the study,
patients have received 28 days of PTC124 treatment at one of three dose
levels. All clinical trial participants are boys with a nonsense mutation
in the dystrophin gene, substantially elevated serum creatine kinase
levels, and symptoms associated with DMD. The analysis presented today
includes data from 26 patients with DMD who received PTC124 at the low-dose
and medium-dose levels. Completion of accrual and analysis of data from a
higher dose level are ongoing.
The primary endpoint of the trial has been the proportion of patients
having an increase in dystrophin expression in muscle during 28 days of
treatment with PTC124. Pre- and post-treatment muscle biopsies were
available from all 26 patients for analysis. In vitro treatment of patient
muscle cells with PTC124 showed evidence of a dose-dependent increase in
dystrophin expression in all of the evaluable patients. Preliminary review
of the data indicate that, at both dose levels evaluated in this analysis,
approximately half of the patients demonstrated visible improvement in the
staining for muscle dystrophin in vivo. Overall, four of the six, or 67
percent, of patients treated at the lower dose level and 10 of the 20, or
50 percent, of patients treated at the medium dose level demonstrated an
increase in the expression of dystrophin post-treatment. Response did not
appear to be dependent on type of nonsense mutation.
Additionally, statistically significant reductions in the
concentrations of muscle-derived creatine kinase levels in the blood were
observed during PTC124 treatment. Several parents and teachers reported
that boys participating in the study had improvements in terms of greater
activity level and increased endurance during treatment. Individual
subjects at both dose levels demonstrated some improvements in upper and
lower muscle strength however in the overall analysis the magnitude of
change was not statistically significant.
PTC124 was well tolerated among the 26 patients included in the study.
Adverse events were infrequent, mild to moderate in severity, and did not
result in therapy interruptions or discontinuations. There were no safety
concerns based on physical examinations, vital sign measurements,
electrocardiograms or laboratory parameters. Compliance with PTC124
treatment was excellent at both dose levels.
Stuart W. Peltz, Ph.D., President and Chief Executive Officer of PTC
Therapeutics, stated, "In addition to the clinical proof-of-concept data we
disclosed late last year, these new insights provide us with further
evidence supporting the potential of PTC124 in genetic disorders due to a
nonsense mutation. The findings in the DMD trials are consistent with the
results observed in Phase 2 clinical trials of PTC124 in patients with
cystic fibrosis and with preclinical results in the DMD mouse model that
were recently published in Nature. We are eager to extend testing of this
concept into other nonsense-mediated genetic disorders."
About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a progressive muscle disorder that
causes the loss of both muscle function and independence. DMD is perhaps
the most prevalent of the muscular dystrophies and is the most common
lethal genetic disorder diagnosed during childhood today. Each year,
approximately 20,000 children worldwide are born with DMD (one of every
3,500 male children). More information regarding DMD is available through
the Muscular Dystrophy Association (http://www.mdausa.org) and the Parent Project
Muscular Dystrophy (http://www.parentprojectmd.org).
About PTC124
PTC124 is an orally delivered investigational new drug in Phase 2
clinical development for the treatment of genetic disorders due to nonsense
mutations. Nonsense mutations are single-point alterations in the genetic
code that prematurely halt the translation process, producing a shortened,
non- functional protein. PTC124 has restored production of full-length,
functional proteins in preclinical genetic disease models harboring
nonsense mutations. In Phase 1 clinical trials, PTC124 was generally well
tolerated, achieved target plasma concentrations that have been associated
with activity in preclinical models and did not induce ribosomal read
through of normal stop codons. PTC is currently conducting Phase 2 clinical
trials of PTC124 in nonsense-mutation-mediated cystic fibrosis (CF) and
Duchenne muscular dystrophy (DMD).
It is estimated that 10% of the cases of CF and 13% of the cases of DMD
are due to nonsense mutations. PTC believes that PTC124 is potentially
applicable to a broad range of other genetic disorders in which a nonsense
mutation is the cause of the disease. The FDA has granted PTC124 Fast-Track
designations and Orphan Drug designations for the treatment of CF and DMD
due to nonsense mutations. PTC124 has also been granted orphan drug status
for the treatment of CF and DMD by the Committee for Orphan Medicinal
Products (COMP) of the European Medicines Agency (EMEA). PTC124's
development is supported by grants from the Muscular Dystrophy Association
(MDA), Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), Parent Project
Muscular Dystrophy (PPMD), FDA's Office of Orphan Products Development
(OOPD) and by General Clinical Research Center grants from the National
Center for Research Resources (NCRR).
About PTC Therapeutics, Inc.
PTC is a biopharmaceutical company focused on the discovery and
development of orally administered, proprietary, small-molecule drugs that
target post-transcriptional control processes. Post-transcriptional control
processes regulate the rate and timing of protein production and are of
central importance to proper cellular function. PTC's internally-discovered
pipeline addresses multiple therapeutic areas, including genetic disorders,
oncology and infectious diseases. In addition, PTC has developed
proprietary technologies and extensive knowledge of post-transcriptional
control processes that it applies in its drug discovery and development
activities, including the Gene Expression Modulation by Small-molecules
(GEMS) technology platform, which has been the basis for collaborations
with leading pharmaceutical and biotechnology companies such as Pfizer, CV
Therapeutics and Schering-Plough.
SOURCE PTC Therapeutics, Inc.
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Related links:
http://www.ptcbio.com
http://www.mdausa.org http://www.parentprojectmd.org
Photo Notes:http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO
CONTACT:
Jane Baj of PTC Therapeutics, Inc.,
+1-908-222-7000, x167, or jbaj@ptcbio.com, or Sheryl Seapy of
Pure Communications, +1-949-608-0841, or
sheryl@purecommunicationsinc.com, for PTC Therapeutics, Inc.
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