- Findings Suggest Clinically Meaningful Primary Endpoint for Clinical
Trials; Data Presented at the 13th International World Muscle Society
Congress -
SOUTH PLAINFIELD, N.J., Sept. 30 /PRNewswire/ -- PTC Therapeutics, Inc.
(PTC) today announced promising findings in patients with Duchenne/Becker
Muscular Dystrophy (DMD/BMD) at the 13th International World Muscle Society
(WMS) Congress. Results from an observational study assessing the utility
of the 6-minute walk test (6MWT) as a primary outcome measure in trials of
treatment for DMD/BMD showed that the 6MWT clearly differentiates boys with
DMD from healthy boys, especially when adjusted for age. The findings also
demonstrate that the 6MWT provides a reliable assessment of ambulatory
function in boys as young as five years of age, offering a practical and
clinically meaningful outcome measure for use in DMD/BMD
registration-directed clinical trials. Results from the study were
presented today by Craig McDonald, M.D., principal investigator and
director of the Rehabilitation Research and Training Center in
Neuromuscular Diseases, University of California Davis.
(Logo: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO )
There has been a strong interest in establishing clinically meaningful
outcomes measures to advance the development of new treatments for DMD/BMD.
The 6MWT is an accepted and standardized measure of ambulatory capacity
that was developed to provide an integrated assessment of cardiac,
respiratory, circulatory and muscular capacity. Until this study, it had
been unclear whether boys with DMD would have the stamina and mental focus
to successfully finish the test without injury. This study demonstrated
that ambulatory boys with DMD as young as five years old can complete the
6MWT safely and reliably with minimal interruption from falls. The study
found that the muscular deficits that are characteristic of boys with DMD
impair their stride length and cadence, resulting in shorter 6-minute walk
distances than healthy boys. The data correlate well with the known natural
history of DMD and suggest that the test should be able to detect treatment
effects on DMD-related muscular deficits.
"The 6MWT evaluates the critical human function of ambulation and is
highly relevant to patients with DMD, who progressively lose walking
ability during childhood," said Dr. McDonald. "Establishing a gold-standard
outcome measure for new therapies in DMD has long been a goal among
researchers. These findings allow us to confidently use changes in the
distance achieved during the 6MWT as a major efficacy endpoint in
therapeutic trials."
These findings directly support the design of an ongoing phase 2b,
double-blind, randomized trial of PTC124 in boys with DMD/BMD, in which the
6MWT is the primary outcome measure. Demographic and baseline data from
this study are also being presented at the WMS Congress today. This
multicenter, international study is enrolling 165 ambulatory boys who are
at least five years old. Today's presentation reports baseline data on the
first 43 subjects, who range in age from 5 to 17 years. Using the 6MWT,
subjects were tested and then retested up to six weeks later; the
correlation between test and retest was high (r=0.93), further
demonstrating the reliability of the 6MWT. In addition to the ongoing phase
2b study, PTC124 is being evaluated in an open-label, long-term extension
study open to boys who participated in an earlier phase 2a trial.
"The findings from these clinical trials contribute provide strong
underpinnings for the design of the PTC124 clinical trials program," said
Langdon Miller, M.D., Chief Medical Officer of PTC Therapeutics, Inc. "We
are hopeful that these data can benefit the entire field of DMD clinical
research and therapeutics development and can establish regulatory
precedent of use of the 6MWT in DMD/BMD"
The study was made possible due to funding provided by the Parent
Project Muscular Dystrophy (PPMD). In an effort to maximize the utility of
the study findings, the PPMD also sponsored the development of a video
demonstrating the 6MWT. The video demonstrates how to perform the test, and
will ensure consistency across clinical trials and will serve as a resource
for clinics using the 6MWT to follow the progress of boys with DMD/BMD.
"Identifying and promoting a clinically meaningful endpoint with proven
utility has been an important goal of our organization. We are thrilled to
be able to help disseminate information about the 6MWT widely, so it can be
quickly and readily integrated into clinical trial protocols," said Pat
Furlong, President and CEO of PPMD.
About DMD/BMD
Duchenne and Becker muscular dystrophy (DMD/BMD) are progressive muscle
disorders that cause the loss of both muscle function and independence.
DMD/BMD 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). It is estimated that one in 10 DMD patients
are likely to have a Becker presentation, a milder form of the disease that
is associated with later manifestation of symptoms. In essence, DMD and BMD
represent a continuum of the same disease. More information regarding DMD
and BMD is available through the Muscular Dystrophy Association
(http://www.mdausa.org), Parent Project Muscular Dystrophy
(http://www.parentprojectmd.org) and the Association Francaise contre les
Myopathies (http://www.afm-france.org).
About PTC124
PTC124 is an orally delivered, investigational new drug discovered by
PTC Therapeutics. The drug is being developed for the treatment of genetic
disorders due to nonsense mutations. Nonsense mutations are single-point
alterations in the genetic code that prematurely stop the translation
process, leading to production of truncated, non-functional proteins.
PTC124 induces the cellular translation machinery to read through nonsense
mutations, inducing production of full-length, functional proteins. PTC124
has demonstrated proof of concept in phase 2a clinical trials. Across all
clinical studies to date, PTC124 has been generally well tolerated. PTC124
is currently in phase 2b development with the goal of demonstrating that
increasing functional protein levels in patients with nonsense-mediated
genetic disorders will safely provide clinical benefits.
PTC124 has been granted orphan drug status by the FDA and the European
Commission for the treatment of cystic fibrosis and DMD due to nonsense
mutations. The FDA has also granted PTC124 Subpart E designation for
expedited development, evaluation, and marketing.
Genzyme Corporation has an exclusive collaboration with PTC to develop
and commercialize PTC124 outside the U.S. and Canada. The development of
PTC124 has also been supported by grants from the Muscular Dystrophy
Association, Parent Project Muscular Dystrophy, FDA's Office of Orphan
Products Development, the National Center for Research Resources and
notably, the Cystic Fibrosis Foundation Therapeutics Inc. (the nonprofit
affiliate of the Cystic Fibrosis Foundation), which recently expanded
support of PTC124 to include funding up to $25 million.
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. PTC has extensive knowledge of post-transcriptional control
processes and has developed proprietary technologies that it applies in its
drug discovery activities, including the Gene Expression Modulation by
Small-molecules (GEMS) technology, which has been the basis for
collaborations with leading biopharmaceutical companies such as Genzyme,
Pfizer, Celgene, CV Therapeutics and Schering-Plough. For more information,
visit the company's website http://www.ptcbio.com.
SOURCE PTC Therapeutics, Inc.
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Related links:
http://www.afm-france.org
http://www.mdausa.org http://www.parentprojectmd.org
http://www.ptcbio.com
Photo Notes: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.,
+1-908-912-9167, jbaj@ptcbio.com; or Sheryl Seapy of Pure
Communications, +1-949-608-0841, sheryl@purecommunicationsinc.com
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