Two of Sarepta’s DMD Drugs Miss Primary Endpoint in Confirmatory Trial
Sarepta Therapeutics reported that two of its Duchenne muscular dystrophy (DMD) drug candidates, AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen), did not meet the primary endpoint in a Phase III confirmatory trial known as the ESSENCE study.
Trial Results
After 96 weeks, the trial showed a difference of 0.05 steps/second in least square means (LSM) between the treatment and placebo groups, which was not statistically significant. However, numerical trends suggested a benefit for the treated group.
Impact of the COVID-19 Pandemic
Sarepta noted the data was “confounded” by the COVID-19 pandemic, which influenced the trial's outcomes over the nine years it was conducted.
Clinical Significance Despite Statistical Outcome
The treatment demonstrated a 30% reduction in decline (LSM 0.11 steps/second) compared to placebo. Although this change was not statistically significant, Sarepta considers it clinically meaningful.
Next Steps with the FDA
Sarepta plans to leverage data from the ESSENCE study, real-world evidence, and the drugs' positive safety profile to seek full FDA approval. The company intends to request a meeting to discuss transitioning from accelerated to traditional approval for AMONDYS 45 and VYONDYS 53.
“Data was confounded by the Covid-19 pandemic.” – Sarepta Therapeutics
“Treatment led to a 30% reduction… which is still not statistically significant, but is a clinically meaningful change.” – Sarepta Therapeutics
Author’s summary: Despite failing to meet statistical endpoints in a long-term trial affected by COVID-19, Sarepta aims to pursue full FDA approval for its DMD drugs based on clinical trends and safety data.