Phase 3 trial of ataluren commences

Sep 11 2009

PTC Therapeutics, Inc. (PTC) today announced the initiation of a Phase 3 trial of ataluren (formerly PTC124(R)), an investigational protein restoration therapy in patients with nonsense mutation cystic fibrosis (nmCF). Patients with CF lack adequate levels of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride channel necessary for normal function of the lung, pancreas, liver, and other organs. In nmCF, an interruption in the genetic code -- known as a nonsense mutation -- prematurely halts the synthesis of CFTR, causing the protein to be short and non-functioning. Nonsense mutations are categorized as Class I mutations that result in little or no production of the CFTR protein. CF patients with Class I mutations typically experience more severe disease symptoms than those with low-risk genotypes, including a greater than twofold increased risk of death, a higher probability of end-stage lung disease, and a higher prevalence of pancreatic insufficiency. Ataluren is designed to promote restoration of the missing CFTR. Through advances in genetic analysis, a simple test can now determine if a patient's disease is caused by a nonsense mutation.

The primary objective of the registration-directed double-blind, placebo-controlled study is to evaluate whether ataluren can improve lung function, as measured by forced expiratory volume in one second (FEV1), in patients with nmCF. Other outcome measures will evaluate whether ataluren can reduce symptoms associated with nmCF, decrease lung infections, reduce the frequency of cough, and improve patient-reported quality of life. The 48-week trial is now enrolling patients at multiple research centers in North America, Europe, and Israel. Study candidates include patients who are at least six years of age and have CF due to a nonsense mutation.

"Promising Phase 2 clinical trial data show that patients treated with ataluren can produce functional CFTR protein, resulting in improvements in chloride channel activity," said Frank Accurso, M.D., Professor of Pediatrics and Section Head of Pulmonary Medicine of the University of Colorado, Denver and a leading ataluren investigator. "With the newly initiated Phase 3 study we hope to determine if the effects of ataluren on the underlying cause of the disease can result in clinical benefit for patients with nmCF."

"As an oral therapy that may address the underlying cause of the disease, ataluren has the potential to improve the management of nmCF for patients and their physicians," said Christiane DeBoeck, M.D., Ph.D., Principal Investigator for University Hospital Leuven. "It is our hope that this long-term clinical trial of ataluren will advance our knowledge of the disease and the standard of care for nmCF patients."

"The initiation of this Phase 3 trial represents an important step forward in our efforts to develop treatments for the underlying cause of cystic fibrosis," said Robert J. Beall, Ph.D., President and CEO of the Cystic Fibrosis Foundation. "Phase 2 studies of ataluren showed encouraging potential to restore CFTR protein production and we are pleased to be supporting this study." In July 2008, Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), the nonprofit affiliate of the Cystic Fibrosis Foundation, expanded its existing collaboration with PTC Therapeutics. PTC will receive up to $25 million from CFFT in support of the development of ataluren.

An orally administered therapy, ataluren is the first investigational new drug designed to enable the formation of a functioning protein in patients with genetic disorders due to a nonsense mutation. Restoring functional CFTR protein may enable ataluren to address the underlying cause of nmCF and change the course of the disease. Currently available therapies for CF focus only on the alleviation of symptoms.

"We are excited to expand the ataluren registration program to include nmCF, an area of significant unmet medical need," said Langdon Miller, M.D., Chief Medical Officer of PTC Therapeutics. "We are hopeful that this Phase 3 trial together with our ongoing studies in nmDMD/BMD, will add to a growing body of data demonstrating ataluren's potential for treatment of patients with nonsense mutation genetic disorders."

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