FDA advisory committee votes against approving Exondys (eteplirsen) for Duchenne muscular dystrophy amenable to exon 51 skipping- Sarepta Therapeutics

Sarepta Therapeutics has announced that the FDA Peripheral and Central Nervous System Advisory Committee (PCNSC) met to review the new drug application for Exondys (eteplirsen) as a treatment for Duchenne muscular dystrophy amenable to exon 51 skipping. The advisory committee voted 6-7 against the finding of substantial evidence from adequate and well controlled studies that show that eteplirsen induces production of dystrophin to a level that is reasonably likely to predict clinical benefit. The advisory committee then voted 3 – 7, with three abstentions, against finding substantial evidence based on the clinical results of the single historically controlled study (Study 201/202) that eteplirsen is effective for treatment of DMD.

The fate of eteplirsen is being closely monitored as a litmus test for an ongoing battle between the patient groups and the FDA, with the former arguing that the agency should be more lenient on therapies for unmet medical needs. In the case of eteplirsen, patients are pinning their hopes on the FDA granting accelerated approval based on the fact that clinical trials have hinted at a benefit for those with DMD.

The FDA can grant accelerated approval to a drug based on preliminary data and wait for confirmation through additional trials. However the FDA raised doubts over the reliability of the 12-patient clinical trial that Sarepta used as evidence for approval, as well as the use of six-minute walking tests that trial participants too part in. The agency must decide by May 26 whether to follow the recommendation.

Comment: In January 2016, the FDA rejected BioMarin Pharmaceutical Inc's Kyndrisa, designed to address the same subset of patients as Sarepta’s drug. This subset - Duchenne muscular dystrophy amenable to exon 51 skipping - represents about 13 percent of all DMD patients, or roughly 1,500 patients in the US.