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 long-term safety and functional outcomes 4 years post-treatment with delandistrogene moxeparvovec in Study 101 (NCT03375164): a Phase 1/2a, single-dose, open-label clinical trial.
Methods: Four ambulatory patients with DMD (≥4 to <8 years old) were enrolled. Patients received an intravenous infusion of delandistrogene moxeparvovec (2.0x10^14 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. Results: 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 (standard deviation [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 (SD) 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.
Conclusions: 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.
This study was sponsored and funded by Sarepta Therapeutics.