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 the safety and efficacy of delandistrogene moxeparvovec, compared with placebo, in patients with DMD aged ≥4 to <8 years. Methods: Study 102 (NCT03769116; N=41) is a Phase 2 study. Part 1 was a 48-week, randomized, double-blind, placebo-controlled period. In Part 2 (48 weeks), patients randomized to placebo in Part 1 received delandistrogene moxeparvovec. Part 3 is an ongoing, ≤212-week, open-label follow-up period. Full analyses from Parts 1 and 2 will be presented. Results: Overall maintenance of the mean North Star Ambulatory Assessment (NSAA) score was observed 96 weeks after delandistrogene moxeparvovec treatment, when functional decline is expected based on natural history. Mean NSAA total score increased by 1.3 points at 48 weeks post-treatment in patients who received placebo in Part 1 and delandistrogene moxeparvovec in Part 2 (aged >5 to <9 years at dosing). In a post hoc analysis, a statistically significant difference of 2 points in mean NSAA total score change from baseline was observed in patients treated in Part 2 versus the propensity-score-weighted external control group (P=0.0009). SRP-9001 dystrophin expression was achieved in all patients treated with delandistrogene moxeparvovec 12 weeks post-treatment. Patients treated in Part 1 continued to express SRP-9001 dystrophin 60 weeks post-treatment. The most common treatment-related treatment-emergent adverse events (AEs) were vomiting, decreased appetite, and nausea. There were no discontinuations due to an AE and no deaths. No new safety signals have been observed in Study 102. Conclusions: Findings from Study 102 reinforce that delandistrogene moxeparvovec has a favorable benefit–risk profile, with no new safety signals observed. Overall maintenance of motor function was observed over 2 years following delandistrogene moxeparvovec treatment. This study was sponsored and funded by Sarepta Therapeutics.