FDA Accepts Resubmission of Translarna NDA for Duchenne

The FDA has accepted the resubmission of the new drug application (NDA) for Translarna (ataluren) to treat nonsense mutation Duchenne muscular dystrophy (nmDMD). Duchenne muscular dystrophy is a rare and fatal genetic disorder that causes progressive muscle weakness, leading to premature death in the mid-20s due to heart and respiratory failure.

Developed by PTC Therapeutics, Translarna is designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation, which is an alteration in the genetic code that prematurely halts the synthesis of an essential protein.

The NDA resubmission is based on findings from the global placebo-controlled trial (Study 041) and the long-term STRIDE registry. In Study-041, the data demonstrated significant benefits of Translarna treatment on key endpoints, including six-minute walk distance, NorthStar Ambulatory Assessment, 10-meter walk/run, and 4-stair climb.

The primary analysis population of a subgroup of enrollees, which did not reach statistical significance on the primary endpoint of six-minute walk. However, significant benefit was recorded across six-minute walk and other key study endpoints in the overall enrolled (ITT) population.

The registry data also showed Translarna delayed loss of ambulation by 3.5 years and reaching a critical lung function threshold by 1.8 years.

Matthew B. Klein

“The NDA acceptance for review is a significant milestone that brings us one step closer to providing this important treatment to boys and young men living with nonsense mutation Duchenne muscular dystrophy in the United States,” Matthew B. Klein, CEO of PTC Therapeutics, said in a news release.

With an NDA resubmission, the FDA is not obligated to follow the standard Prescription Drug User Fee Act (PDUFA) review timeline, so an action date has not been provided.

The company has struggled to demonstrate to regulatory officials the efficacy of Translarna. The FDA had issued a complete response letter in 2017, saying additional clinical trials would be necessary to provide substantial evidence of effectiveness.

And earlier this month, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency issued a negative opinion — its second negative opinion — on the renewal of the conditional marketing authorization of Translarna. But the marketing authorization in Europe remains in effect until the European Commission issues a final decision, which is expected in about 67 days. In 2023, Translarna generated $356 million of revenue.