Sarepta Therapeutics says the FDA has agreed to review a regulatory package for Amondys 45 and Vyondys 53 after they failed a confirmatory trial, but whether the agency will agree to approve them is still unknown.
Sarepta Therapeutics will forge on with a traditional approval request to the FDA for the Duchenne muscular dystrophy exon skippers Amondys 45 and Vyondys 53, after receiving the agency’s blessing to submit additional information from an unsuccessful confirmatory trial.
Whether the FDA will deem that additional data worthy of converting the existing accelerated approvals to full, traditional approvals, however, will be determined during the review, Sarepta said in a Thursday press release. If the FDA does not accept the exon skippers for full approval, they could be pulled from the market.
Sarepta received accelerated approval for Amondys 45 in 2021 and Vyondys 53 in 2019, contingent on conducting a confirmatory clinical trial to show clinical benefit of the Duchenne muscular dystrophy (DMD) therapies. The results of those studies came in last year, with neither improving motor function.
After receiving the results, Sarepta requested a meeting with the FDA to discuss the conversion of the accelerated approvals into traditional nods. The company brought data from the confirmatory trial, called ESSENCE, real-world data plus safety data suggesting the therapies have a favorable profile.
The FDA agreed to accept the data as part of the supplemental new drug application, however, “the adequacy of the data to support conversion to traditional approval will be a matter of review,” Sarepta said on Thursday.
“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,” Louise Rodino‑Klapac, president of research & development and technical operations at Sarepta, said in a statement.
The neuromuscular-focused company plans to submit the revised application by the end of April.
Sarepta noted that the ESSENCE study was conducted over a period of time that included the COVID-19 pandemic, which it said impacted the outcome. While the trial did not meet its primary endpoint of improvement in number of steps taken, the results did show “numerical trends” toward the therapies’ benefit.
Now, Sarepta has taken another look at the data and excluded 23 participants, or 10% of the population, whose step data was taken during the COVID-19 impact period.
The real-world data comes from the over 1,800 patients who have received one of the exon skippers, including patients as young as 7 months to adults in their 30s. The results for Vyondys 53 show a 7.5 year delay in the need for nighttime ventilation while Amondys 45 demonstrated a statistically significant slowing of lung function decline and a potential benefit in time to use of a cough assist device. These data also suggest a multi-year survival benefit and delay in the time to loss of ambulation of three to four years, among other potential benefits, according to Sarepta.
The plan to go ahead with the Amondys 45 and Vyondys 53 filings comes at a difficult and transitional time for Sarepta. CEO Doug Ingram announced his planned departure at the end of the year, as the company tries to come back from a brutal year of regulatory and clinical challenges.
Besides the exon skipper failures, multiple deaths were attributed to Sarepta’s gene therapy products, including the approved DMD therapy Elevidys. This led to weakening sales as reported during fourth quarter and full year earnings in February.
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