EMBARK Trial: Delandistrogene Moxeparvovec in Duchenne Muscular Dystrophy

Study at a glance:

• Journal: Nature Medicine, 2025

• Population: Ambulatory boys aged 4–7 years with Duchenne muscular dystrophy

• Method: Phase 3, randomized, placebo-controlled trial assessing single-administration intravenous delandistrogene moxeparvovec

• Key Finding: No significant improvement in North Star Ambulatory Assessment (NSAA) score at 52 weeks; manageable safety profile

Summary:
The EMBARK study evaluated the efficacy and safety of delandistrogene moxeparvovec, a viral vector-based gene therapy, in boys with Duchenne muscular dystrophy (DMD). A total of 125 patients were randomized to receive either delandistrogene moxeparvovec (n = 63) or placebo (n = 62). The primary endpoint was the change in NSAA score at 52 weeks, which showed a non-significant difference between treatment and placebo (2.57 vs 1.92 points; between-group difference 0.65; 95% CI, -0.45 to 1.74; P = 0.2441). Secondary endpoints, including micro-dystrophin expression, timed functional tests, and mobility measures, showed some numerical favor toward treatment but were not statistically significant. Safety was consistent with prior studies: no deaths or discontinuations occurred, and 11.1% of treated patients experienced treatment-related serious adverse events, which were manageable.

Takeaway:
Delandistrogene moxeparvovec did not significantly improve functional outcomes in ambulatory boys with DMD at 52 weeks, though some secondary measures favored treatment, and the safety profile was acceptable.

Source: Mendell JR, Muntoni F, McDonald CM, et al. AAV gene therapy for Duchenne muscular dystrophy: The EMBARK phase 3 randomized trial. Nat Med. 2025;31(1):332-341. doi:10.1038/s41591-024-03304-z  Available at: https://www.nature.com/articles/s41591-024-03304-z