Sarepta’s Duchenne Muscular Dystrophy Drugs Fail Confirmatory Trial, Company Pursues Full FDA Approval Regardless

Sarepta’s Phase III confirmatory trial for Duchenne muscular dystrophy drugs AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen) failed to meet its primary endpoint, showing no statistically significant benefit over placebo after 96 weeks1 3 7.

Despite this failure, Sarepta will seek full (traditional) US FDA approval based on numerical trends favoring treatment, accumulated real-world evidence, and positive safety profiles of the drugs1 3 5.

The trial was affected by confounding factors, including the COVID-19 pandemic, but Sarepta claims clinically meaningful functional outcomes and a 30% reduction in decline (though still not statistically significant)1 3.

Sarepta’s gene therapy Elevidys also failed to meet its primary efficacy endpoint in the EMBARK study (functional mobility after 52 weeks), but the company will pursue a label expansion, citing benefits in secondary endpoints and FDA openness to consider the 'totality of the evidence'2 4 5.

All four Sarepta Duchenne drugs currently on the market were approved via the FDA’s accelerated pathway; none has yet been unambiguously proven to slow disease progression in confirmatory trials2.

Experts and some critics see the lack of statistically significant findings as insufficient for full approval, while Sarepta emphasizes clinically meaningful trends and broader real-world evidence2 3.

FDA faces a difficult decision:
options range from rescinding current approvals to granting full approval or maintaining accelerated approval; physician confidence may be shaken by unclear efficacy2.