Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy developed to address the root cause of Duchenne muscular dystrophy (DMD) through targeted skeletal and cardiac muscle expression of SRP-9001 dystrophin protein, which contains key functional domains of dystrophin.
Objective: To evaluate functional data in patients with DMD ≥4 to ≤8 years of age at Year 1 following a single intravenous (IV) infusion of delandistrogene moxeparvovec versus a propensity-score-weighted external control (EC) cohort.
Methods: Ambulatory patients with DMD ≥4 to ≤8 years of age received a single IV infusion of delandistrogene moxeparvovec (1.33×10^14 vg/kg, linear standard qPCR).
The dataset included patients treated with clinical process delandistrogene moxeparvovec material (Study 101, Phase 1/2a; NCT03375164 and Study 102, Phase 2; NCT03769116) and intended commercial process delandistrogene moxeparvovec material (ENDEAVOR, Phase 1b; NCT04626674). Data were compared with a propensity-score-weighted EC cohort (N=131), comprised of natural history and external clinical trial data from three studies. The primary endpoint was 1-year change from baseline in North Star Ambulatory Assessment (NSAA) total score. Exploratory endpoints included the effect on key timed function tests 1 year post-treatment. Collective safety data available from Study 101, Study 102 and ENDEAVOR are also presented.
Results: The integrated analysis evaluated functional data from 52 patients, including patients from Study 101 (N=4), Study 102 (n=28) and Cohort 1 of ENDEAVOR (n=20). Results showed a statistically significant difference of 2.4 points (P<0.0001) in NSAA change from baseline to Year 1 in treated patients versus the EC cohort (n=105). In a collective safety analysis from the three studies, there were no adverse events that led to study discontinuation and no deaths. Conclusions: Delandistrogene moxeparvovec demonstrated a clinically meaningful and statistically significant difference versus a propensity-score-weighted EC cohort in change from baseline in NSAA total score at 1 year, suggesting a beneficial modification of the DMD disease trajectory. Collective safety data were consistent and manageable across studies. Studies 101 and 102 and ENDEAVOR were sponsored and funded by Sarepta Therapeutics. ENDEAVOR was also funded by F. Hoffmann-La Roche Ltd.