Three-Year Follow-Up of Delandistrogene Moxeparvovec in Duchenne Muscular Dystrophy: Long-Term Phase 3 EMBARK Trial Results.

Authors

Jerry R Mendell, Francesco Muntoni, Craig M McDonald, Eugenio M Mercuri, Nicolas Deconinck, Emma Ciafaloni, Hirofumi Komaki, Carmen Leon-Astudillo, Andrés Nascimento, Crystal Proud, Ulrike Schara-Schmidt, Aravindhan Veerapandiyan, Craig M Zaidman, Matthew Furgerson, Damon R Asher, Mark Vivien, Yi Sun, Alexander P Murphy, Pooneh Pordeli, Carmen O Torre, Marianna Manfrini, Marianne Gerber, Louise R Rodino-Klapac, EMBARK Study Group

Published in

Neurology and therapy. Oct 27, 2026. Epub Oct 27, 2026.

Abstract

Delandistrogene moxeparvovec, an adeno-associated virus vector-based gene therapy, delivers an optimized micro-dystrophin transgene to address dystrophin deficiency in Duchenne muscular dystrophy (DMD). EMBARK was a phase 3, randomized, double-blind, placebo-controlled, two-part crossover study evaluating the safety and effectiveness of delandistrogene moxeparvovec in patients with DMD who are ambulatory aged ≥ 4 to < 8 years. After completion of the EMBARK study at 2 years, patients had the option to enroll into the long-term follow-up open-label EXPEDITION study.
Three-year functional outcomes from patients treated with delandistrogene moxeparvovec in EMBARK part 1 (single intravenous dose 1.33 × 10¹⁴ vg/kg; n = 64) were compared with a matched propensity score weighted external control (EC) cohort (n = 143) derived from randomized controlled clinical trials (patients treated with placebo only) and natural history datasets. Mixed-effects models for repeated measures accounted for missing data and estimated changes from baseline and between-cohort differences. All P values are nominal.
At 3 years post-infusion, patients treated in part 1 of EMBARK (aged 7-10 years at 3 years) suggested sustained and statistically significant differences versus the matched EC cohort in change from baseline in North Star Ambulatory Assessment total score (between-cohort least-squares mean difference, 4.39 points; P = 0.0002), Time to Rise (- 6.05 s; P < 0.0001), and 10-m Walk/Run (- 2.70 s; P = 0.0039), suggesting durable slowing of disease progression. No new safety signals were identified through year 3, with no emerging cardiac safety concerns as the left ventricular ejection fraction remained above the normal threshold of 55% in this population over 3 years. There were no treatment-related deaths or discontinuations due to adverse events during follow-up.
The 3-year follow-up of patients with DMD who are ambulatory treated in EMBARK part 1 compared with external comparators suggests durable functional benefit and a consistent safety profile following treatment with delandistrogene moxeparvovec, which may indicate long-term disease trajectory modification and increasing divergence from natural history over time. Graphical abstract available for this article.
EMBARK: NCT05096221; EXPEDITION: NCT05967351.

PMID:
42944976
Bibliographic data and abstract were imported from PubMed on 28 Oct 2026.

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