Another DMD pipeline setback

In another setback for the Duchenne muscular dystrophy community, the Food & Drug Administration has refused to consider PTC Therapeutics’ New Drug Application for ataluren.

DMD is a rare, fatal disease caused by a mutation in the gene responsible for producing dystrophin, a protein that is critical for muscle strength. Ataluren is designed to restore functional protein in the 10–15% of boys whose DMD is caused by a “nonsense” mutation.

PTC had filed for U.S. approval despite a failed Phase III clinical trial and was banking on signs of efficacy in a subset of patients in an earlier Phase II trial. The results for that subset had won it conditional approval in Europe, where full approval is contingent on completion of a Phase III study.

Now, industry watchers wonder whther the drug will be pulled in Europe. “Logic would probably suggest that a regulatory agency would not want a drug that has failed to confirm its efficacy on the market,” RBC Capital Markets stock analyst Simos Simeonidis wrote in a note to investors. “We do, however, acknowledge the difficulty associated with removing the first drug approved for DMD from the market.”

The red light for ataluren is the latest in a string of disappointments for the DMD community. Last month FDA rejected BioMarin’s New Drug Application for drisapersen, an oligonucleotide-based therapeutic that addresses boys whose DMD is caused by a deletion in exon 51 of the dystrophin gene. The agency then delayed its review of Sarepta Therapeutics’ eteplirsen, a similar oligonucleotide.

And a study of Akashi Therapeutics’ HT-100, which treats inflammation and fibrosis associated with DMD, was suspended after a patient taking the highest dose of the drug died. The company is investigating whether the death is linked to its treatment.