EMBARK 2: Delandistrogene Moxeparvovec Shows Sustained Benefits in DMD

Ambulatory patients with Duchenne muscular dystrophy (DMD) who received delandistrogene moxeparvovec-rokl (Elevidys; Sarepta Therapeutics) experienced clinically meaningful, statistically significant functional benefits compared with external controls, according to topline results from part 2 of the EMBARK trial (NCT05096221).¹

“As a neuromuscular medicine specialist who has seen patients with Duchenne muscular dystrophy for over three decades, I’ve witnessed firsthand the positive impact of gene therapy on the trajectory of Duchenne,” Craig McDonald, MD, professor and chair of the UC Davis Health Department of Physical Medicine and Rehabilitation, and an EMBARK study investigator, said in a statement. “These longer-term results are even more striking when compared to external control given the progressive nature of the disease, and we’d expect to see this divergence grow over time. The efficacy of [delandistrogene moxeparvovec] gives me great hope as we continue to follow these patients and see others treated in the clinical setting.”

Delandistrogene moxeparvovec is the only approved gene therapy for DMD. The therapy was initially approved for patients aged 4 through 5 years in 2023, and the FDA expanded its approval in 2024 to include patients 4 years and older.^2,3 The expanded approval included traditional approval in ambulatory patients and accelerated approval in nonambulatory patients.

Duchenne muscular dystrophy | Image credit: hafakot - stock.adobe.com

The new topline EMBARK results included crossover-treated patients who received a placebo in part 1 of the randomized, double-blind, placebo-controlled study and crossed over at 52 weeks to receive the gene therapy (n = 59).¹ These patients experienced a 2.34-point increase on the North Star Ambulatory Assessment (NSAA)—a measure of functional motor abilities in ambulant patients with DMD—from baseline to 52 weeks after receiving delandistrogene moxeparvovec (P < .0001). The study remained blinded during the crossover period.

Patients in the crossover group were 1 year older than the patients treated in part 1, with an average age of 7.18 years. Still, they experienced a clinically meaningful and statistically significant improvements in NSAA score, time to rise (–2.70 seconds improvement; P < .0001), and the 10-meter walk/run test (–1.07 seconds improvement; P = .0001) compared with an external control group.

“We’re very encouraged to see the results from Part 2 of EMBARK as they further elucidate the impact [delandistrogene moxeparvovec] has on disease progression in a blinded, controlled study,” Louise Rodino-Klapac, PhD, executive vice president, head of research and development, and chief scientific officer at Sarepta Therapeutics, said in a statement. “Skeletal muscle MRI demonstrates the importance of preserving muscle, and the functional outcome results show disease stabilization sustained through 2 years after treatment.”

At year 2, skeletal muscle MRIs done on patients who were treated in part 1 of the study showed minimal disease progression and were consistent with the observed functional benefits. There were no new safety signals reported in the updated results.

“Over time, we continue to observe a statistically significant difference favoring [delandistrogene moxeparvovec] compared to a well-matched external control on NSAA and timed tests,” Rodino-Klapac said. “The consistency and totality of evidence supporting a long-term and clinically meaningful treatment benefit with [delandistrogene moxeparvovec] continues to grow. We look forward to sharing more details with the clinical community in upcoming scientific forums.”

References

1. Sarepta Therapeutics announces results from part 2 of the EMBARK study demonstrating sustained benefits and disease stabilization in ambulatory individuals with Duchenne muscular dystrophy following treatment with Elevidys. News release. Sarepta Therapeutics. January 27, 2025. Accessed January 28, 2025.

2. Caffrey M. FDA Approves Delandistrogene Moxeparvovec, First Gene Therapy to Treat Duchenne Muscular Dystrophy. The American Journal of Managed Care^®. June 22, 2023. Accessed January 28, 2025. https://www.ajmc.com/view/fda-approves-delandistrogene-moxeparvovec-first-gene-therapy-to-treat-duchenne-muscular-dystrophy

3. Shaw M. FDA grants 2 approvals to delandistrogene moxeparvovec for DMD. The American Journal of Managed Care®. June 20, 2024. Accessed January 28. 2025. https://www.ajmc.com/view/fda-grants-2-approvals-to-delandistrogene-moxeparvovec-for-dmd