PTC
Therapeutics Announces Additional Positive Interim Phase 2 Results
of PTC124 in Duchenne Muscular Dystrophy
Data
Presented at 59th
BOSTON,
MA and SOUTH PLAINFIELD, NJ – May 4, 2007
- 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 creatine kinase values in at least
50 percent of evaluable patients. These data were presented today at the
59th
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
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
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 (www.mdausa.org) and the Parent Project Muscular Dystrophy
(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
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.
For more information
Jane
Baj PTC
Therapeutics, Inc. (908)
222-7000, x167 jbaj@ptcbio.com |
Sheryl
Seapy Pure
Communications (949)
608-0841 |