Ataluren Fails to Pass Muster as Treatment for Severe Form of Cystic Fibrosis

PTC Therapeutics’ ataluren has failed to significantly improve respiratory function in nonsense mutation cystic fibrosis (nmCF), a severe form of the disease, according to results of a Phase 3 clinical trial.

“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,” Stuart Peltz, PhD, PTC Therapeutics’s CEO, said in a news release. “We are particularly grateful to patients and investigators who participated in our trials. We remain committed to patients receiving ataluren in other indications.”

The company plans to abandon its effort to continue developing ataluren as a cystic fibrosis treatment. Ataluren will continue to be marketed in Europe for nonsense mutation Duchenne muscular dystrophy, however.

Nonsense mutation cystic fibrosis limits or prevents the production of the CFTR protein, which is involved in the proper functioning of the lungs.

The Phase 3 trial (ACT CF; NCT02139306) of ataluren, whose European brand name is Translarna, included 279 nmCF patients 6 years and older who were not receiving chronic inhaled aminoglycosides. Participants were randomized to receive ataluren three times a day for 48 weeks, or a placebo. Ataluren doses were 40 mg/kg/day.

The study’s primary endpoint, or yardstick, was improvement in lung function. It was measured by the change in patients’ percent-predicted FEV1 — or forced expiratory volume in one second — from the start of the study to the 48th week.

Secondary endpoints included rate of pulmonary exacerbations, or flare-ups; respiratory health-related quality of life; and measurements of body weight and body mass index (BMI) from baseline to week 48.

Ataluren offered only a 0.6 percent difference in FEV1. Although it decreased the rate of pulmonary exacerbations by 14 percent compared with a placebo, neither of the results was significant.

The treatment was well-tolerated, and its safety profile was consistent with that of previous studies of the drug. There were no reports of new side effects.

PTC plans to halt the clinical development of ataluren as a possible treatment for CF, halt its current extension studies of the treatment, and withdraw its application for European marketing authorization for the drug.

Ataluren is marketed in the European Economic Area to treat those 5 years and older with nonsense mutation Duchenne muscular dystrophy.

Its development has been supported by Cystic Fibrosis Foundation Therapeutics, the Muscular Dystrophy Association, and the U.S. Food and Drug Administration’s Office of Orphan Products Development.