Sarepta Therapeutics (SRPT) Study result summary

Study design and methodology

• EMBARK is a global, double-blind, placebo-controlled Phase 3 trial in ambulatory boys aged 4–7 with Duchenne muscular dystrophy, randomizing 125 patients to receive a single IV infusion of ELEVIDYS or placebo, with a crossover to active treatment after one year and long-term follow-up up to five years.

• After year one, all participants received ELEVIDYS, and years two and three used a propensity-weighted external control group matched for baseline characteristics, with over 70 EC patients at three years.

• Functional outcomes assessed included North Star Ambulatory Assessment (NSAA), time to arise (TTR), and 10-meter walk/run (10MWR), all pre-specified as co-primary endpoints.

• Key inclusion criteria included NSAA score 17–28 and time to rise <5 seconds at screening.

• The three-year analysis included data from the EMBARK trial and its long-term extension, representing the largest long-term gene therapy follow-up in DMD.

Key efficacy results

• ELEVIDYS-treated patients showed a 4.39-point higher NSAA score at year three versus external controls (p=0.0002), nearly double the year two difference.

• Time to arise improved by 6.05 seconds compared to controls, reflecting a 73% slowing of disease progression and a threefold widening of treatment effect since year two.

• The 10-meter walk/run showed a 2.7-second benefit (p=0.0039), indicating a 70% slowing of progression and a doubling of separation from controls between years two and three.

• Treated patients remained above baseline function at three years, while controls declined significantly.

• Only two treated patients lost ambulation over three years, about half the rate seen in external controls.

Safety and tolerability

• No new safety signals or treatment-related serious adverse events were observed in year three; safety profile remained consistent with known risks.

• Common adverse reactions included vomiting, nausea, liver injury, fever, thrombocytopenia, and increased troponin-I.

• Boxed warning for acute serious liver injury and acute liver failure; monitoring and corticosteroid use are required.

• Dropouts between years two and three were mainly for personal reasons, with no evidence of bias or impact on results.

• No treatment-related deaths reported; one unrelated death disclosed.