- New Pediatric Data Presented at 21st North American Cystic Fibrosis
Conference Confirm Previous Findings in Adult population -
SOUTH PLAINFIELD, N.J., Oct. 5 /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 encouraging data
from a Phase 2 clinical trial of PTC124 in pediatric patients with cystic
fibrosis (CF) due to a nonsense mutation. These pediatric results and
additional information emerging from long-term studies support the existing
data from prior short- term studies in adult CF patients. These studies
show that treatment with PTC124 results in statistically significant
improvements in a measure of the function of the cystic fibrosis
transmembrane conductance regulator (CFTR) protein. These data were
highlighted today in a plenary session entitled "CF Drug Development:
What's New?" given by Dr. Felix Ratjen, University of Toronto Professor of
Pediatrics and Respiratory Medicine Division Chief, at the 21st North
American Cystic Fibrosis Conference in Anaheim, California.
(Logo: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO )
Patients with CF lack the CFTR protein, a chloride channel that
maintains proper hydration of epithelial cells in the lung, pancreas, and
liver. PTC has completed multi-site, open-label, dose-ranging Phase 2
clinical trials in adult CF patients to determine whether PTC124 can induce
production of active CFTR protein. Studies in the U.S. and Israel evaluated
nasal transepithelial potential difference (TEPD) as a surrogate for CFTR
protein production in adult CF patients. Across the two studies, at both
PTC124 dose levels tested, TEPD assessments showed statistically
significant (p<0.03) improvements of mean CFTR-dependent chloride secretion
in the airways.
PTC is currently conducting a third, open-label, dose-ranging Phase 2
clinical trial in pediatric CF patients at l'Hopital Necker-Enfants Malade,
Paris, France to determine whether PTC124 can induce production of active
CFTR protein. In the trial, patients receive two sequential two-week
courses of treatment. Patients have been randomized to receive either a low
or high dose of PTC124 followed by two weeks of rest and then are crossed
over to the other dose level for an additional two weeks of therapy. Eleven
patients have completed the study and data from these patients were
available for inclusion in the initial analysis. Across both dose levels,
statistically significant improvements (p<0.05) were seen in CFTR
chloride-channel function as measured by TEPD.
"Our initial observations in a pediatric population confirm the
findings from the previous studies in older CF patients," said Isabelle
Sermet- Gaudelus, M.D., Ph.D., principal investigator at l'Hopital
Necker-Enfants Malade, Paris, France. "Normalization of CFTR-mediated
chloride secretion was observed in several of the children, indicating that
PTC124 continues to demonstrate significant potential as a treatment for
patients with CF. Based on the enthusiasm generated by these data, we have
recently added two new study sites in Belgium in order to expand the
evaluation of PTC124 across a larger pediatric population."
Eitan Kerem, M.D., Head of Pediatrics and the CF Center at the Hadassah
University Hospital in Mount Scopus, Jerusalem also commented on
longer-term studies that he has been leading in Israel. "Based on the
positive results we observed during our initial study with two-week
treatment periods, we have analyzed preliminary data from a three-month
extension study evaluating the longer-term effect of PTC124 in patients
with nonsense-mutation-mediated CF. We have seen encouraging evidence of
sustained CFTR chloride-channel function and improvements in symptoms of
CF, such as coughing, which we believe may be predictive of longer-term
clinical benefit. We look forward to presenting the full data from this
trial next year."
"We are very pleased to see the evidence of drug activity reported at
last year's North American Cystic Fibrosis Conference reproduced by
additional investigators in a pediatric population," said Langdon Miller,
M.D, Chief Medical Officer of PTC. "We are also encouraged by the findings
of the Israeli three-month study. We believe these confirmatory results,
coupled with supportive safety data in more than 50 patients participating
in the Phase 2 trial program, can lead to initiation of longer-term trials
to evaluate the clinical benefit of PTC124 in patients with CF."
About Cystic Fibrosis
Cystic fibrosis (CF) is among the most common life-threatening genetic
disorders worldwide. According to the Cystic Fibrosis Foundation, CF
affects approximately 30,000 adults and children in the United States and,
according to the European Cystic Fibrosis Foundation, it affects a similar
number of patients in Europe. CF occurs in approximately one of every 3,500
live births, with approximately 1,000 new cases diagnosed each year in the
United States. 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% of patients in
the United States. 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 a treatment for 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 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 Celgene, Pfizer, CV Therapeutics and
Schering- Plough.
SOURCE PTC Therapeutics, Inc.
 back to top
Related links:
http://www.ptcbio.com
http://www.cff.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, Ext. 167, jbaj@ptcbio.com; or Sheryl Seapy of
Pure Communications, +1-949-608-0841,
sheryl@purecommunicationsinc.com
|
