To evaluate long-term safety and functional outcomes 4 years post-treatment with delandistrogene moxeparvovec (SRP-9001) in Study 101 (NCT03375164): a Phase 1/2a, single-dose, open-label clinical trial.

Delandistrogene moxeparvovec 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.

Four ambulatory patients with DMD (≥4 to <8 years old) were enrolled. Patients received an intravenous infusion of delandistrogene moxeparvovec (2.0x10¹⁴ vg/kg) and prednisone (1 mg/kg/day), 1-day pre- to 30-days post-treatment. The primary outcome was safety. Secondary outcomes included SRP-9001 dystrophin expression. Key efficacy outcomes included change from baseline in North Star Ambulatory Assessment (NSAA) and timed function tests.

A total of 72 adverse events were reported, the majority of which occurred in the first 70-days post-treatment and 18 (25.0%) of which were treatment-related. At 4 years post-treatment, no new safety events were reported. There was an improvement in function, with a change from baseline in mean (SD) NSAA at 90 days and 1 year of 5.3 (1.0) and 5.5 (2.7) points, respectively. Delandistrogene moxeparvovec demonstrated sustained stabilization of function 4 years post-treatment, with a mean 7-point (2.9) increase from baseline in NSAA. Similar trends were observed for timed function tests, including Time to Rise, 4-stair Climb, and 10- and 100-meter Walk/Run.

In a post-hoc analysis, delandistrogene moxeparvovec showed a statistically significant difference >9 points in mean change from baseline NSAA at 4 years versus a propensity-score-weighted external control cohort (?=9.4, SE=3.4; P=0.0125), far exceeding the threshold for a clinically meaningful difference.

Delandistrogene moxeparvovec was well tolerated with no new safety signals 4-years post-treatment. Functional assessments demonstrated long-term, sustained, clinically meaningful improvement in motor function at ages where functional decline would be expected based on natural history.