Cystic Fibrosis Drug Translarna Fails Phase 3 Test

Company walks away from protein-restoration therapy

PTC Therapeutics has announced that its phase 3 Ataluren Confirmatory Trial (ACT) in patients with nonsense-mutation cystic fibrosis (nmCF) did not achieve its primary or secondary endpoints. PTC plans to discontinue clinical development of ataluren (Translarna) for CF; to close ongoing extension studies; and to withdraw its application for marketing authorization for CF in Europe.

The ACT trial was a 48-week, double-blind, placebo-controlled study comparing ataluren with placebo in nmCF patients 6 years of age or older who were not receiving chronic inhaled aminoglycosides. The study enrolled a total of 279 patients in 16 countries. The primary endpoint of lung function, as measured by the absolute change in percent-predicted forced expiratory volume in one second (FEV1) at 48 weeks from baseline, showed a 0.6% difference in favor of ataluren compared with placebo (–1.4% change vs. –2.0%, respectively; P = 0.534). For the secondary endpoint of the rate of pulmonary exacerbations, the rate in the ataluren group was 14% lower than that in the placebo group (P = 0.401).

Ataluren 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 an investigational new drug in the United States.

Source: PTC Therapeutics; March 2, 2017.