Two Sarepta Therapeutics medication for treating completely different genetic subsets of sufferers with Duchenne muscular dystrophy failed the confirmatory study required of their accelerated FDA approvals. Sarepta executives say there’s nonetheless a path for conventional FDA approval, however it may depend on regulatory flexibility that the company has proven towards the corporate and different builders of therapies for uncommon ailments.
Sarepta’s Vyondys 53, approved in 2019, and Amondys 45, approved in 2021, each obtained their speedy regulatory nods primarily based on scientific trial outcomes exhibiting remedy led to increased ranges of dystrophin, a key muscle protein that Duchenne sufferers lack. However these antisense oligonucleotide medication have been nonetheless required to bear testing in an extended and bigger confirmatory examine designed to evaluate sufferers on a variety of muscle perform measures.
After Monday’s market shut, Sarepta reported preliminary Section 3 outcomes exhibiting remedy with the Duchenne medication led to numerically higher however not statistically important enchancment on the primary objective measuring the time it takes for a affected person to climb 4 steps. Sarepta stated the detrimental final result of the nine-year examine was as a result of Covid-19 pandemic, throughout which 43% of impacted members had consecutive missed doses of the once-weekly infused medication. On common, examine members missed eight consecutive doses.
Excluding knowledge from the 57 members whose double-blind dosing interval overlapped with the pandemic, Sarepta stated outcomes present a 30% discount in illness development in comparison with placebo over two years as measured in response to the four-step take a look at. Talking throughout a Monday night convention name, Sarepta CEO Doug Ingram acknowledged that excluding the 57 Covid-impacted examine members reduces the ability of the examine. However he stated the change for the remaining 168 sufferers is clinically significant. Ingram added that it’s essential to take an extended view of the Duchenne medication.
“One of many good issues about having these therapies commercially obtainable for thus lengthy is that we get to see what occurs over the long run,” Ingram stated. “You have a look at [Vyondys] for six years, and these children are seeing actually nearly three years of delay in being in a wheelchair and the time to air flow is considerably completely different.”
Medication that fails confirmatory research can have their advertising and marketing authorization revoked. Ingram doesn’t see that occuring to Vyondys and Amondys primarily based on Sarepta’s prior discussions with the FDA. In response to Ingram, the company stated the usual for withdrawing advertising and marketing authorization is “solely in a situation the place no related analyses would affirm scientific profit.” He added that the scientific trial and actual world proof proceed to help affected person profit. The corporate plans to debate with the FDA transitioning the Duchenne medication’ standing to conventional regulatory approvals.
Sarepta didn’t disclose outcomes for the trial’s secondary objectives. However Louise Rodino-Klapac, the corporate’s president, R&D and technical operations, stated that these objectives, which embody further measures of muscle perform in addition to organic endpoints, can be introduced at a future medical assembly.
Sarepta has had a tough yr. Three patients who received Sarepta gene therapies died in 2025. Two of those sufferers received Sarepta’s Elevidys, a Duchenne gene remedy that controversially converted its accelerated approval to a traditional one final yr regardless of failing its confirmatory scientific trial. All three fatalities have been attributed to acute liver failure. Elevidys stays obtainable to Duchenne sufferers who can nonetheless stroll, however not for these whose illness has progressed to the purpose the place they’re non-ambulatory. Discussions with the FDA are ongoing concerning modifications to the Elevidys immunosuppression routine to cut back the liver harm threat.
Sarepta’s monetary report for the third quarter of 2025 reveals $399.4 million in income, down 14.5% in comparison with the identical interval within the prior yr. The corporate attributed the decrease income to the discount in Elevidys shipments. That places extra stress on Sarepta’s chronically administered Duchenne therapies to generate income, however monetary analysts don’t share the corporate’s optimism about these medication. In a word despatched to buyers Tuesday, William Blair analyst Sami Corwin stated the Section 3 examine’s failure to satisfy its essential objective is a detrimental improvement.
“Regardless of administration’s confidence that Vyondys 53 and Amondys 45 won’t lose advertising and marketing authorization consequently, we’re extra skeptical, and suppose the inventory’s response (down 37% after hours) suggests buyers are additionally involved about the way forward for these two merchandise,” Corwin wrote.
Photograph: Dina Mariani, Getty Photos
