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

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.


  1. Meredith Kates says:

    My husband participated in this study, and he was an outlier (significantly improved overall health, BMI and maintaining lung function). Why isn’t there compassionate care medicine provided to patients who benefited and complied with the study fully?

  2. Jacqueline Kates says:

    What about those patients who have been doing well, whose lung function improved, and whose overall health improved greatly on the drug? My son-in-law gained 15 pounds. He shouldn’t have to give up this medication when it has made such a difference in his life. There isn’t an alternative. It shouldn’t be taken away from him. What can we do so that he can stay on this drug?

    • Tim Bossie says:

      Hi Jacqueline, that is a very real concern for many people. The drug, while it is not passing through approval because of those it has failed to produce any type of success from, is working in others who are not part of the survey. We (CFNews) hope that your son in law does not have to lose access from this drug since he is doing well on it.

  3. Meredith Kates says:

    This drug did not “fizzle” for many patients. Some gained over 20 pounds in a year, showed improved overall health and lung function. LF numbers may not have improved statistically, but maintaining and improving overall health should have been considered as endpoints. Please provide a means for patients showing improvement to access this drug via compassionate care. We have been fighting and racing time, and the survival of some CF patients with less common mutations are dependent on access. Thank you!

  4. Mary Henderson says:

    Hello, this medicine works well for people with cystic fibrosis. Everyone I know and used has had a significant improvement in both the lung and the pancreas. Why do you think it does not work? This is the only cure for nonsense mutation. I think people are entitled to this medicine, just like my son.

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