Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged ≥4 to <8 Years) with Duchenne Muscular Dystrophy: 1‐Year Interim Results from Study SRP‐9001‐103 (ENDEAVOR)

Abstract

ObjectiveDelandistrogene moxeparvovec is approved in the USA for the treatment of ambulatory patients (4–5 years) with Duchenne muscular dystrophy. ENDEAVOR (SRP‐9001‐103; NCT04626674) is a single‐arm, open‐label study to evaluate delandistrogene moxeparvovec micro‐dystrophin expression, safety, and functional outcomes following administration of commercial process delandistrogene moxeparvovec.MethodsIn cohort 1 of ENDEAVOR (N = 20), eligible ambulatory males, aged ≥4 to <8 years, received a single intravenous infusion of delandistrogene moxeparvovec (1.33 × 1014 vg/kg). The primary endpoint was change from baseline (CFBL) to week 12 in delandistrogene moxeparvovec micro‐dystrophin by western blot. Additional endpoints evaluated included: safety; vector genome copies; CFBL to week 12 in muscle fiber‐localized micro‐dystrophin by immunofluorescence; and functional assessments, including North Star Ambulatory Assessment, with comparison with a propensity score‐weighted external natural history control.ResultsThe 1‐year safety profile of commercial process delandistrogene moxeparvovec in ENDEAVOR was consistent with safety data reported in other delandistrogene moxeparvovec trials (NCT03375164 and NCT03769116). Delandistrogene moxeparvovec micro‐dystrophin expression was robust, with sarcolemmal localization at week 12; mean (SD) CFBL in western blot, 54.2% (42.6); p < 0.0001. At 1 year, patients demonstrated stabilized or improved North Star Ambulatory Assessment total scores; mean (SD) CFBL, +4.0 (3.5). Treatment versus a propensity score‐weighted external natural history control demonstrated a statistically significant difference in least squares mean (standard error) CFBL in North Star Ambulatory Assessment, +3.2 (0.6) points; p < 0.0001.InterpretationResults confirm efficient transduction of muscle by delandistrogene moxeparvovec. One‐year post‐treatment, delandistrogene moxeparvovec was well tolerated, and demonstrated stabilized or improved motor function, suggesting a clinical benefit for patients with Duchenne muscular dystrophy. ANN NEUROL 2023;94:955–968