EMBARK
Trial question
What is the role of delandistrogene moxeparvovec in patients with Duchenne muscular dystrophy?
Study design
Multi-center
Double blinded
RCT
Population
125 male patients.
Inclusion criteria: male patients aged 4-8 years with Duchenne muscular dystrophy who are ambulatory.
Key exclusion criteria: Duchenne muscular dystrophy gene with pathogenic variants between or including exons 1-17; LVEF < 40%; major surgery in the past 3 months; clinically significant illness; symptomatic infection in the past 4 weeks.
Interventions
N=63 delandistrogene moxeparvovec (single intravenous administration of 1.33×10**14 vg/kg).
N=62 placebo (single intravenous administration of 0.9% sodium chloride).
Primary outcome
Improvement in least squares mean North Star Ambulatory Assessment score at week 52
2.57 points
1.92 points
2.6 points
1.9 points
1.3 points
0.6 points
0.0 points
Delandistrogene
moxeparvovec
Placebo
No significant
difference ↔
No significant difference in improvement in least squares mean North Star Ambulatory Assessment score at week 52 (2.57 points vs. 1.92 points; MD 0.65, 95% CI -0.45 to 1.74).
Secondary outcomes
Significant increase in least squares mean reduction in time to rise from the floor at week 52 (0.27 seconds vs. -0.37 seconds; MD 0.64, 95% CI 0.23 to 1.06).
Significant increase in least squares mean reduction in 10-meter walk/run at week 52 (0.34 seconds vs. -0.08 seconds; MD 0.42, 95% CI 0.13 to 0.71).
Significant increase in least squares mean reduction in time to ascend 4 steps at week 52 (0.44 seconds vs. 0.08 seconds; MD 0.36, 95% CI 0.01 to 0.71).
Safety outcomes
No significant difference in adverse events.
Conclusion
In male patients aged 4-8 years with Duchenne muscular dystrophy who are ambulatory, delandistrogene moxeparvovec was not superior to placebo with respect to improvement in least squares mean North Star Ambulatory Assessment score at week 52.
Reference
Jerry R Mendell, Francesco Muntoni, Craig M McDonald et al. AAV gene therapy for Duchenne muscular dystrophy: the EMBARK phase 3 randomized trial. Nat Med. 2025 Jan;31(1):332-341.
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