Sarepta Therapeutics announced on Mar. 19 that it will move forward with a request for traditional approval from the Food and Drug Administration (FDA) for its Duchenne muscular dystrophy exon skipping therapies, Amondys 45 and Vyondys 53. The company said it received the agency’s agreement to submit additional data from a confirmatory trial that did not meet its primary endpoint.
The decision is significant because Sarepta’s therapies were previously granted accelerated approval, which required successful confirmatory trials to demonstrate clinical benefit. If the FDA does not accept the new data as sufficient for full approval, Amondys 45 and Vyondys 53 could be withdrawn from the market.
Sarepta was granted accelerated approval for Amondys 45 in 2021 and Vyondys 53 in 2019, contingent on positive results from follow-up studies. However, last year’s ESSENCE trial showed neither therapy improved motor function. After these results, Sarepta met with the FDA to discuss converting the accelerated approvals into traditional ones by presenting data from ESSENCE, real-world evidence, and safety information suggesting a favorable profile.
The FDA agreed to review this supplemental information but stated that “the adequacy of the data to support conversion to traditional approval will be a matter of review,” according to Sarepta. Louise Rodino‑Klapac, president of research & development and technical operations at Sarepta, said in a statement: “In rare diseases like Duchenne, where progression varies widely and meaningful functional changes unfold over years—not months—incorporating real-world data alongside clinical findings can help us better understand long-term outcomes. This is especially true for therapies targeting ultra-rare, genetically defined subgroups, where confirmatory studies are inherently complex.”
Sarepta plans to submit its revised application by the end of April. The company noted that the ESSENCE study took place during the COVID-19 pandemic and excluded some participants whose step data was collected during this period when reassessing results. Real-world data includes outcomes from more than 1,800 patients treated with one of the exon skippers; reported benefits include delayed need for nighttime ventilation with Vyondys 53 and slowed lung function decline with Amondys 45.
This regulatory effort comes amid broader challenges for Sarepta. CEO Doug Ingram recently announced he will step down at year’s end as the company faces declining sales of its gene therapy Elevidys following multiple deaths linked to its products.
