- Data Presented at the 31st European Cystic Fibrosis Conference -
SOUTH PLAINFIELD, N.J. and PRAGUE, Czech Republic, June 12 /PRNewswire/
-- PTC Therapeutics, Inc. (PTC) today announced promising new data from two
studies of PTC124 in cystic fibrosis (CF). Results from an Israeli Phase 2a
extension study evaluating three months of oral PTC124 treatment in adult
patients with nonsense-mutation-mediated CF demonstrated statistically
significant improvements in the function of the cystic fibrosis
transmembrane conductance regulator (CFTR) protein and a statistically
significant mean [28%] decrease in the frequency of cough, one of the most
prominent and burdensome CF-related symptoms. Results from the Hadassah
University Hospital in Israel were presented today by Michael Wilschanski,
M.D., Director, Pediatric Gastroenterology, and by Eitan Kerem, M.D.,
principal investigator and head of the Department of Pediatrics and Cystic
Fibrosis Center. Separately, results from a European study evaluating
14-day courses of PTC124 in pediatric patients with
nonsense-mutation-mediated CF confirmed the CFTR activity observed in
previous short-term studies in adult patients. Data from the European study
were presented today by Isabelle Sermet-Gaudelus, M.D., Ph.D., principal
investigator at l'Hopital Necker-Enfants Malade.
(Logo: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO )
Patients with CF lack adequate levels of the CFTR protein, a chloride
channel that maintains proper hydration of epithelial surfaces in the lung,
pancreas, and liver. Patients with nonsense-mutation-mediated CF generally
have a severe form of CF because virtually no CFTR protein is produced.
Previous studies of PTC124 adult patients with CF evaluated nasal
transepithelial potential difference (TEPD) as a surrogate for the presence
and activity of the CFTR protein. Across the short- and long-term clinical
trials at high and low doses of PTC124, TEPD assessments showed
statistically significant improvements of mean CFTR-dependent chloride
secretion in the airways.
The Phase 2a extension study in Israel assessed 3 months of oral PTC124
therapy at two different dose levels in 19 adult men and women with
nonsense- mutation-mediated CF who had participated in a prior short-term
PTC124 Phase 2a study. More than 90% of the patients had chronic CF-related
lung infection and also had CF-induced pancreatic insufficiency. Results
from the study showed that treatment with PTC124 resulted in statistically
significant (p< 0.001) improvements in CFTR function as measured by TEPD in
both dose groups. The proportion of patients showing improvement in TEPD
chloride secretion increased over time in the extension study. Trends
towards improvements in mean FEV1 and FVC values were observed. Baseline
data showed that CF patients cough a remarkable 643 times per day on
average, with a range of 324 to 1,569 coughs per day. In comparison,
healthy individuals generally cough fewer than 16 times per day, according
to the European Respiratory Journal (Hsu 1994). Patients receiving PTC124
experienced a mean [28%] decrease in cough frequency by the end of three
months of therapy (p< 0.01). PTC124 was generally well tolerated, resulting
in excellent mean compliance with the treatment regimen ( >90%).
"Three months of treatment with PTC124 in nonsense-mutation-mediated CF
patients was associated with time-dependent improvements in nasal TEPD
chloride conductance, pulmonary function and cough -- important markers
suggesting the potential for benefit in patients with CF," stated Dr.
Wilschanski. "PTC124 increases CFTR-mediated chloride secretion in patients
with a variety of nonsense mutation types, which suggests a broad spectrum
of activity across one of the major subpopulations in CF."
Dr. Kerem added, "The impact on cough that we observed in this study by
objective measurement is particularly notable given that cough is one of
the major symptomatic manifestations of the underlying disease process in
CF. The reduction in cough achieved with PTC124 in this three-month study
suggests secondary clinical effects of drug activity. Based on these
findings, we believe that objective measurement of cough may offer a
meaningful new way to evaluate drug efficacy in future CF clinical trials."
In a separate Phase 2a study in Europe, data are currently available
from 21 children who received two 14-day treatment courses of oral PTC124
therapy at two different dose levels. Patients ranged in age from six to 18
years. All had nonsense-mutation-mediated disease, pathological lung
infection, and pancreatic insufficiency. Statistically significant (p<
0.05) increases in the proportion of epithelial cells showing surface
staining with the CFTR protein were observed. In addition, statistically
significant (p< 0.05) improvements in CFTR-mediated chloride conductance as
measured by TEPD were evident. PTC124 was generally well tolerated in
pediatric patients and mean compliance with treatment was excellent (
>95%).
"We are encouraged to see the activity of PTC124 observed in adults
reproduced in a pediatric population in France and Belgium," commented Dr.
Sermet-Gaudelus. "PTC124 causes the missing protein to be made, to be
located in the right place in the cell, and to have functional effect.
Combined with the generally well-tolerated profile of PTC124, we believe
these data support inclusion of pediatric patients in future clinical
trials."
"We are gratified by these results from our Israeli, French, and
Belgian investigators, which demonstrated the activity of PTC124 in
patients across a variety of age ranges, geographies, and nonsense mutation
types," stated Langdon Miller, M.D., Chief Medical Officer of PTC. "These
data offer the basis for initiating a randomized, controlled Phase 2b study
later this year to evaluate the clinical benefit of PTC124 in adults and
children with nonsense-mutation-mediated 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. 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 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 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, preventing production of a functional
protein. In Phase 2a clinical trials in nonsense-mutation-mediated cystic
fibrosis (CF) and in nonsense-mutation-mediated Duchenne muscular dystrophy
(DMD), PTC124 has demonstrated the ability to produce functional protein
across a variety of nonsense mutation types. Across all clinical studies to
date, PTC124 has been generally well tolerated and has achieved target
plasma concentrations that have been associated with activity in
preclinical models. PTC124 is currently in Phase 2b development with the
goal of demonstrating that increasing functional protein levels in patients
with nonsense-mediated genetic disorders may provide clinical benefits.
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. For more information, visit the company's website,
http://www.ptcbio.com.
SOURCE PTC Therapeutics, Inc.
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CONTACT:
Investors and Media, 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, for PTC Therapeutics, Inc.; or
Patients, Patients' Families, and Patient Organizations, Diane
Goetz of PTC Therapeutics, Inc., +1-908-912-9256,
patientinfo@ptcbio.com
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