Data Presented at the World Muscle Society International Congress
SOUTH PLAINFIELD, N.J., Oct. 18 /PRNewswire/ -- PTC Therapeutics, Inc.
(PTC), a biopharmaceutical company focused on the discovery, development,
and commercialization of small-molecule drugs targeting
post-transcriptional control mechanisms, today announced additional data
from a Phase 2 clinical trial of PTC124 in patients with Duchenne muscular
dystrophy (DMD) due to a nonsense mutation. The results, which include data
from all three cohorts of the study, show that administration of PTC124 is
associated with qualitative increases in muscle dystrophin expression and
with reductions in serum creatine kinase values. These data were presented
today at the World Muscle Society (WMS) International Congress in Taormina,
Italy.
(Logo: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO )
Patients with DMD are boys and young men who 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 enrolled 38 boys with
loss of dystrophin due to a nonsense mutation in the dystrophin gene.
Participants also had substantially elevated serum creatine kinase levels
due to the disease, and symptoms associated with DMD. Boys enrolled in the
trial received 28 days of PTC124 treatment at one of three dose levels,
with the primary endpoint of the trial being an increase in dystrophin
expression in muscle. Pre- and post-treatment muscle biopsies and blood
analyses to assess muscle-derived creatine kinase were available from all
38 patients.
An in vitro analysis demonstrated PTC124-induced dystrophin expression
in cultured muscle cells from all 35 (100%) of the boys with samples
evaluable in this analysis. The in vivo data indicated that, across all
three dose levels of PTC124, 18/38 (47%) of patients demonstrated visible
improvement in the staining for dystrophin from muscle biopsies. Response
did not appear to be dependent on type of nonsense mutation.
Blood levels of muscle-derived creatine kinase were also measured as
assessments of muscle integrity. Statistically significant reductions in
the concentrations of muscle-derived creatine kinase were observed during
PTC124 treatment. In addition, several parents and teachers reported that
boys participating in the study had improvements in terms of greater
activity level and increased endurance during the study duration.
"We are very encouraged by these results, which show improvements in
critical biomarkers of DMD," said presenter and study investigator, Carsten
Bonnemann, M.D., Assistant Professor Neurology and Pediatrics, Children's
Hospital of Philadelphia and University of Pennsylvania School of Medicine
and Co-Director of the Neuromuscular Program, Children's Hospital of
Philadelphia. "The combined in vitro and in vivo evidence of enhanced
dystrophin expression and reduced muscle fragility offer signals of
pharmacological activity that we hope to translate into potential clinical
benefit for patients with DMD."
"Coupled with the emerging safety profile of PTC124, these data provide
the impetus for moving forward rapidly to initiate longer-term studies for
boys with DMD," said Langdon Miller, M.D., Chief Medical Officer of PTC.
"We are actively working with our clinical investigators and the regulatory
agencies to finalize plans for additional clinical trials and we look
forward to commencing these studies in the coming months."
Stuart W. Peltz, Ph.D., President and Chief Executive Officer of PTC
Therapeutics added, "These results, combined with the data presented
earlier this month at the Child Neurology Society meeting and North
American Cystic Fibrosis Conference, further support our belief that PTC124
represents a paradigm shift in the treatment of genetic disorders. Our
future plans for PTC124 include the initiation of longer-term studies in
DMD and cystic fibrosis (CF) as well as additional proof of concept studies
in other indications. We hope that PTC124 will one day offer an improved
treatment option for patients with nonsense-mediated DMD, CF, and a broad
range of 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 European Commission. 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,
development and commercialization 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, Celgene, 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:
NewsCom: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO
AP Archive: http://photoarchive.ap.org
PRN Photo Desk, photodesk@prnewswire.com
CONTACT:
Jane Baj of PTC Therapeutics, Inc.,
+1-908-222-7000, x167, jbaj@ptcbio.com; or Sheryl Seapy of Pure
Communications, +1-949-608-0841,
sheryl@purecommunicationsinc.com, for PTC Therapeutics, Inc.
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