Gene Therapy Improves Motor Function but Misses Primary Endpoint in Duchenne Muscular Dystrophy Trial

The single-dose gene therapy Elevidys (delandistrogene moxeparvovec-rokl) increased motor function per the North Star Ambulatory Assessment (NSAA) in children ages 4 through 7 years with Duchenne muscular dystrophy compared with placebo, according to topline results from a phase 3 trial announced by maker Sarepta Therapeutics Inc. Nevertheless, statistical significance on the primary endpoint of NSAA total score change was not met.

The blinded, two-part EMBARK trial involved children ages 4 through 7 with Duchenne muscular dystrophy. In Part 1, 125 participants were randomized to Elevidys or placebo with a follow-up period of 52 weeks. In Part 2, participants crossed over to the alternate intervention, with a 52-week follow-up.

At 52 weeks after treatment, patients improved 2.6 points on NSAA total score with Elevidys and 1.9 points with placebo. The 0.65-point difference between treatments failed to reach statistical significance, Sarepta reported.

Meanwhile, key prespecified functional secondary endpoints, including time to rise and the 10-meter walk test, showed robust evidence for a clinically meaningful benefit across age groups with Elevidys, compared with placebo, at 52 weeks, the company announced.

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“The results favored Elevidys across all endpoints in the study, including achieving statistical significance on all prespecified key secondary endpoints and in each age subgroup of the key secondary endpoints,” said Doug Ingram, Sarepta’s president and chief executive officer. “Indeed, passing 5 seconds on time to rise is the strongest predictor of early loss of ambulation, and in EMBARK Elevidys reduced those odds over 52 weeks by greater than 90%.”

Stride velocity 95th centile, time to ascend 4 steps, and all other timed functional endpoints demonstrated benefit in favor of Elevidys, according to the company.

“The consistency of the positive effect across all timed function tests and age groups provides evidence of a meaningful treatment effect,” said study investigator Craig McDonald, MD, professor and chair of the department of physical medicine and rehabilitation at the University of California, Davis, California. “In addition, it is important to note that this is the first clinical trial in the history of Duchenne muscular dystrophy trials to show a statistically significant and meaningful improvement on the novel measure of 95th centile stride velocity derived from an objective community wearable activity monitor.”

Sarepta plans to share full results from the trial at future medical meetings.  

Reference

Sarepta Therapeutics announces topline results from EMBARK, a global pivotal study of ELEVIDYS gene therapy for Duchenne muscular dystrophy. News release. Sarepta Therapeutics; October 30, 2023. Accessed November 17, 2023.