PTC Therapeutics, Inc.,a global biopharmaceutical company, announced that the Ataluren Confirmatory Trial (ACT CF) in nonsense mutation cystic fibrosis (nmCF) did not achieve its primary or secondary endpoints.
Ataluren was generally well tolerated and ACT CF confirmed a favorable safety profile for ataluren, which has now been used by more than 1,000 patients across multiple indications. PTC plans to discontinue current clinical development of ataluren in cystic fibrosis, close ongoing extension studies and withdraw its application for marketing authorization in cystic fibrosis in Europe.
"We are disappointed with the outcome of this trial as there are no treatments that target the underlying cause of nonsense mutation cystic fibrosis, one of the most difficult forms to treat," said Stuart W. Peltz, Ph.D., chief executive officer of PTC Therapeutics. "We are particularly grateful to patients and investigators who participated in our trials. We remain committed to patients receiving ataluren in other indications."
ACT CF was a double-blind, placebo-controlled, 48-week clinical trial comparing ataluren to placebo in nmCF patients six years of age or older not receiving chronic inhaled aminoglycosides. The phase 3 study, conducted in 16 countries, enrolled 279 patients who were randomized to receive either ataluren or placebo. In the intent-to-treat population, the primary endpoint of lung function as measured by absolute change in percent-predicted FEV1 (forced expiratory volume in one second), over 48 weeks from baseline, there was a 0.6% difference in favor of ataluren versus placebo (-1.4% change on ataluren versus -2.0% change on placebo; p=0.534). For the secondary endpoint of rate of pulmonary exacerbations, there was a trend in favor of ataluren, with the rate in the ataluren group being 14% lower than the placebo group (p=0.401). The results were not statistically significant.
The safety profile of ataluren in the ACT CF study was consistent with previous studies and no new safety signals were identified.
Ataluren (brand name: Translarna), discovered and developed by PTC Therapeutics, Inc., is a protein restoration therapy designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation. A nonsense mutation is an alteration in the genetic code that prematurely halts the synthesis of an essential protein. The resulting disorder is determined by which protein cannot be expressed in its entirety and is no longer functional, such as dystrophin in Duchenne muscular dystrophy. Ataluren is licensed in the European Economic Area for the treatment of nonsense mutation Duchenne muscular dystrophy in ambulatory patients aged five years and older. Ataluren is an investigational new drug in the United States. The development of ataluren has been supported by grants from Cystic Fibrosis Foundation Therapeutics Inc. (the nonprofit affiliate of the Cystic Fibrosis Foundation); Muscular Dystrophy Association; FDA's Office of Orphan Products Development; National Center for Research Resources; National Heart, Lung, and Blood Institute; and Parent Project Muscular Dystrophy.
PTC is a global biopharmaceutical company focused on the discovery, development and commercialization of orally administered, proprietary small molecule drugs targeting an area of RNA biology.