- One of the First Therapies to Address the Underlying Cause of Cystic
Fibrosis; Oral Drug May Represent New Treatment Paradigm -
SOUTH PLAINFIELD, N.J., Aug. 20 /PRNewswire/ -- New phase 2 data
published today in The Lancet show that the investigational oral drug
PTC124 demonstrates activity in nonsense-mutation cystic fibrosis (CF). The
data show that treatment with PTC124 results in statistically significant
improvements in the chloride channel function of patients with
nonsense-mutation CF. The study was conducted at the Hadassah Hebrew
University Hospital in Jerusalem, Israel and sponsored by PTC Therapeutics
(PTC).
(Logo: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO )
Patients with CF lack adequate levels of the cystic fibrosis
transmembrane conductance regulator (CFTR) protein, a chloride channel
which is required for normal function of the lung, pancreas, liver, and
other organs. Nonsense mutations are single-point alterations in the
genetic code that prematurely stop the translation process, preventing
production of a full-length, functional protein. Patients with
nonsense-mutation CF generally make virtually no CFTR protein and thus
often have a more severe form of CF. By inducing the production of
functional CFTR, PTC124 is addressing the underlying genetic defect
responsible for CF. Nonsense mutations are responsible for approximately 10
percent of the cases of cystic fibrosis worldwide. However, in Israel,
nonsense mutations are responsible for the majority of CF cases.
Study results: PTC124 Restored Functional Production of CFTR Protein in
Patients
This Phase 2 Israeli study enrolled 23 adult patients (median age 25
years) with nonsense-mutation CF. More than 90 percent of patients had
severe CF with compromised lung function, pulmonary infection with
Pseudomonas or other pathogenic bacteria, and pancreatic insufficiency.
Patients were assessed in two 14-day treatment courses of oral PTC124
therapy, the first given at a lower dose and the second given at a higher
dose. Results showed that at both dose levels, treatment with PTC124 was
associated with statistically significant improvements (p<0.05) in
CFTR-mediated chloride transport with over half of the patients entering
the normal range during at least one treatment course. PTC124 induced
chloride transport responses and normalization of CFTR activity across the
variety of patient genotypes tested. Improvements in lung function values
and body weight were also observed. PTC124 was generally well tolerated and
all patients had >90 percent treatment compliance.
"This study demonstrates the potential for personalized medicine,
combining selection of patients with a specific type of genetic mutation
and a drug treatment that has been specifically designed to overcome that
mutation," said Eitan Kerem, MD, head of pediatrics and the CF center at
the Hadassah University Hospital in Mount Scopus, Jerusalem and the lead
author of the study. "The publication of these ground-breaking results in
the Lancet offers new hope to those patients with CF due to a nonsense
mutation in the CFTR gene and establishes a path forward for evaluating the
efficacy and long-term safety of PTC124."
"We are very pleased by this positive outcome from our ongoing
collaboration with PTC," noted Preston Campbell, III, M.D., Executive Vice
President of Medical Affairs at the Cystic Fibrosis Foundation. "The
development of PTC124 fits well with our strategic goal of supporting
approaches that have the potential to modify the course of CF. We are
continuing to work together with PTC and the broader CF medical community
to support the next steps in the evaluation of PTC124 for the clinical
benefit for the treatment of nonsense-mutation CF."
"The publication of these data provides clinical proof of concept in CF
for the PTC124 mechanism of action in overcoming nonsense mutations as the
basis for treating genetic disease," said Stuart W. Peltz, Ph.D., President
and Chief Executive Officer of PTC Therapeutics. "Based on these results,
we intend to initiate a Phase 2b study later this year to evaluate the
clinical benefit of PTC124 in adults and children with
nonsense-mutation-mediated CF. Given the potential applicability of PTC124
to multiple genetic disorders, we have a pivotal study of PTC124 for
nonsense-mutation Duchenne/Becker muscular dystrophy ongoing and are
planning proof-of-concept studies in additional genetic disorders."
The paper entitled "Effectiveness of PTC124 treatment of cystic
fibrosis caused by nonsense mutations: a prospective phase II trial" is
available in an advanced online publication of Lancet on Thursday, August
21st (http://www.lancet.com).
About Cystic Fibrosis
Cystic fibrosis (CF) is a life-threatening genetic disease that causes
serious lung infections and digestive complications. According to the
Cystic Fibrosis Foundation, CF affects approximately 30,000 adults and
children in the United States and nearly 70,000 people worldwide. There is
a commercially available genetic test to determine if a patient's CF is
caused by a nonsense mutation, and it is estimated that nonsense mutations
are the cause of CF in approximately 10 percent of patients in the United
States and Europe and over 50 percent of patients in Israel. There is
currently no available therapy to correct defective CFTR production and
function. Instead, available treatments for CF are designed to alleviate
the symptoms of the disease. These treatments include chest physical
therapy to clear the thick mucus from the lungs, antibiotics to treat lung
infections, and a mucus-thinning drug designed to reduce the number of lung
infections and improve lung function. In addition, the majority of cystic
fibrosis patients take pancreatic enzyme supplements to assist with food
absorption in digestion. There is a significant unmet medical need for
treatments that address the underlying cause of CF. More information
regarding CF is available through the Cystic Fibrosis Foundation
(http://www.cff.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 CF and DMD due to nonsense mutations. The
FDA has also granted PTC124 Subpart E designation for expedited
development, evaluation, and marketing.
PTC has an exclusive collaboration with Genzyme Corporation 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.cff.org
http://www.lancet.com http://www.ptcbio.com
Photo Notes:http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO
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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