Two Sarepta Therapeutics drugs for treating different genetic subsets of patients with Duchenne muscular dystrophy failed the confirmatory study required of their accelerated FDA approvals. Sarepta executives say there’s still a path for traditional FDA approval, but it might rely on regulatory flexibility that the agency has shown toward the company and other developers of therapies for rare diseases.
Sarepta’s Vyondys 53, approved in 2019, and Amondys 45, approved in 2021, both received their speedy regulatory nods based on clinical trial results showing treatment led to higher levels of dystrophin, a key muscle protein that Duchenne patients lack. But these antisense oligonucleotide drugs were still required to undergo testing in a longer and larger confirmatory study designed to assess patients on a range of muscle function measures.
After Monday’s market close, Sarepta reported preliminary Phase 3 results showing treatment with the Duchenne drugs led to numerically better but not statistically significant improvement on the main goal measuring the time it takes for a patient to climb four steps. Sarepta said the negative outcome of the nine-year study was due to the Covid-19 pandemic, during which 43% of impacted participants had consecutive missed doses of the once-weekly infused drugs. On average, study participants missed eight consecutive doses.
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Excluding data from the 57 participants whose double-blind dosing period overlapped with the pandemic, Sarepta said results show a 30% reduction in disease progression compared to placebo over two years as measured according to the four-step test. Speaking during a Monday evening conference call, Sarepta CEO Doug Ingram acknowledged that excluding the 57 Covid-impacted study participants reduces the power of the study. But he said the change for the remaining 168 patients is clinically meaningful. Ingram added that it’s important to take a long view of the Duchenne drugs.
“One of the nice things about having these therapies commercially available for so long is that we get to see what happens over the long term,” Ingram said. “You look at [Vyondys] for six years, and these kids are seeing literally almost three years of delay in being in a wheelchair and the time to ventilation is significantly different.”
Drugs that fails confirmatory studies can have their marketing authorization revoked. Ingram does not see that happening to Vyondys and Amondys based on Sarepta’s prior discussions with the FDA. According to Ingram, the agency said the standard for withdrawing marketing authorization is “only in a scenario where no relevant analyses would confirm clinical benefit.” He added that the clinical trial and real world evidence continue to support patient benefit. The company plans to discuss with the FDA transitioning the Duchenne drugs’ status to traditional regulatory approvals.
Sarepta did not disclose results for the trial’s secondary goals. But Louise Rodino-Klapac, the company’s president, R&D and technical operations, said that these goals, which encompass additional measures of muscle function as well as biological endpoints, will be presented at a future medical meeting.
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Sarepta has had a rough year. Three patients who received Sarepta gene therapies died in 2025. Two of these patients received Sarepta’s Elevidys, a Duchenne gene therapy that controversially converted its accelerated approval to a traditional one last year despite failing its confirmatory clinical trial. All three fatalities were attributed to acute liver failure. Elevidys remains available to Duchenne patients who can still walk, but not for those whose disease has progressed to the point where they are non-ambulatory. Discussions with the FDA are ongoing regarding changes to the Elevidys immunosuppression regimen to reduce the liver injury risk.
Sarepta’s financial report for the third quarter of 2025 shows $399.4 million in revenue, down 14.5% compared to the same period in the prior year. The company attributed the lower revenue to the reduction in Elevidys shipments. That puts more pressure on Sarepta’s chronically administered Duchenne therapies to generate revenue, but financial analysts don’t share the company’s optimism about these drugs. In a note sent to investors Tuesday, William Blair analyst Sami Corwin said the Phase 3 study’s failure to meet its main goal is a negative development.
“Despite management’s confidence that Vyondys 53 and Amondys 45 will not lose marketing authorization as a result, we are more skeptical, and think the stock’s reaction (down 37% after hours) suggests investors are also concerned about the future of these two products,” Corwin wrote.
Photo: Dina Mariani, Getty Images