CAMBRIDGE, Mass. — Sarepta Therapeutics, Inc. said it plans to submit supplemental new drug applications to the U.S. Food and Drug Administration by the end of April 2026 seeking to convert the accelerated approvals of AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen) to traditional approvals for the treatment of Duchenne muscular dystrophy.
The company said its submission will be supported by data from the ESSENCE confirmatory study, along with published real-world evidence and established safety profiles for both therapies. Sarepta reported that the FDA has provided feedback confirming that data from ESSENCE and real-world studies can be included in the applications, with final determination to be made during the agency’s review.
“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,” said Louise Rodino-Klapac, Ph.D., president of research & development and technical operations, Sarepta. “We appreciate the FDA’s openness to our submitting the supplemental applications for AMONDYS 45 and VYONDYS 53 and willingness to consider all available data – from the ESSENCE confirmatory study and the real-world evidence generated over the past several years.”
AMONDYS 45 and VYONDYS 53 are exon-skipping therapies currently approved under the FDA’s accelerated approval pathway for patients with Duchenne muscular dystrophy whose genetic mutations are amenable to exon 45 and exon 53 skipping, respectively.
The ESSENCE trial is a global Phase 3 randomized, double-blind, placebo-controlled study evaluating the therapies in 225 patients ages 6 to 13. Topline results presented at the 2026 Muscular Dystrophy Association Clinical & Scientific Congress showed numerical trends favoring treatment over placebo, but the primary endpoint did not reach statistical significance, with a difference of 0.06 steps per second in 4-step ascend velocity at 96 weeks (P=0.309).
An updated analysis excluding data from patients affected by the COVID-19 pandemic showed an improved difference of 0.12 steps per second at 96 weeks, reaching nominal statistical significance (P=0.050).
No new safety signals were observed in the study, with most adverse events reported as mild or moderate and comparable between treatment and placebo groups, reinforcing the therapies’ established safety profiles.
Sarepta said its phosphorodiamidate morpholino oligomer platform has been used to treat more than 1,800 patients worldwide, with real-world evidence suggesting potential long-term benefits including delayed disease progression, improved respiratory outcomes, and reduced hospitalizations.
VYONDYS 53 works by binding to exon 53 of dystrophin pre-mRNA, enabling exon skipping during mRNA processing and allowing for production of a shortened but functional dystrophin protein. The therapy is approved under accelerated approval based on increased dystrophin production, with continued approval contingent on confirmation of clinical benefit in ongoing studies. (Source: IANS)
