PTC, after multiple FDA rejections, will try again with Translarna

Despite Translarna's troubled history at the FDA—and a recent regulatory stumble in Europe—PTC Therapeutics once again hopes to convince U.S. regulators of the value of its Duchenne muscular dystrophy (DMD) therapy.

Tuesday, the company revealed that it plans to resubmit Translarna to the FDA for the treatment of nonsense mutation DMD by the middle of the year. The decision is based on "recent feedback" and comes after FDA rejections of the drug in 2016 and 2017.

In its first rejection of the drug, the FDA told the company the application wasn't sufficiently complete. In the second rejection, the agency raised flags about a lack of clinical evidence and other shortfalls in PTC's filing.

More recently, European regulators in January issued a negative opinion on renewing the DMD drug's authorization nearly a decade after its debut there. That decision came after a negative recommendation in September 2023 and a multi-month appeal process.

At the time of the latest decision, PTC CEO Matthew Klein said the developments "will result in the withdrawal" of Translarna in Europe.

In deciding against renewing the drug's authorization, Europe's Committee for Medicinal Products for Human Use looked at Translarna’s data from the placebo-controlled Study 041, plus other trials. In Study 041, the PTC drug failed to meet statistical significance on its primary endpoint in a selected patient subgroup, but it did turn in "nominally statistically significant results on several key endpoints," the company argued.

The study's primary endpoint looked at changes from baseline in a six-minute walking distance test. Even as PTC stood behind the medicine, the European Medicines Agency stated bluntly that the study "failed to confirm Translarna's effectiveness."

After the Study 041 results dropped, the FDA told the company that the new trial doesn't provide enough evidence of benefit to support a resubmission, according to a PTC quarterly filing from last year. In response, PTC said it would request a meeting with the agency "to review the “totality of data collected to date."

On a recent conference call, Klein said the company had a meeting scheduled for this month with the agency.

Besides the Translarna development, PTC on Tuesday said it has submitted a biologics license application for Upstaza to treat aromatic L-amino acid decarboxylase deficiency to the FDA.