FDA CRL - Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc. received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA) 211970 for Vyondys 53 (golodirsen) injection. The application sought accelerated approval under the Federal Food, Drug, and Cosmetic Act, based on a surrogate marker, truncated dystrophin.The FDA determined that the application could not be approved due to significant concerns regarding both clinical efficacy and safety. While Study 4053-101 showed a modest mean increase of 0.92% in truncated dystrophin, the FDA concluded that any potential clinical benefit would be commensurately small. Furthermore, 6-minute walk test data indicated progressive loss of physical function with no correlation to dystrophin production, further questioning the drug's clinical effect.Crucially, the FDA identified two major safety issues: serious infections related to drug delivery and renal toxicity, both potentially life-threatening. The agency discovered multiple reports of severe infections, including bacteremia, sepsis, septic shock, and deaths, associated with eteplirsen (a related drug), which were not disclosed or discussed within the golodirsen NDA. This omission of critical safety information was a significant concern. To address these issues, Sarepta must resolve the efficacy concerns and thoroughly investigate and present all relevant safety data, particularly regarding the serious infections.