Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy developed for targeted skeletal and cardiac muscle expression of micro-dystrophin, a shortened, functional dystrophin protein.
Objective: This Phase 1/2a, single-dose, open-label clinical trial (NCT03375164) evaluates the safety of systemic gene transfer of delandistrogene moxeparvovec in patients with Duchenne muscular dystrophy (DMD).
Results: Four ambulatory patients with DMD (4–7 years old) were enrolled. Patients were given an intravenous infusion of delandistrogene moxeparvovec at a dose of 2.0×1014 vg/kg (supercoiled qPCR, linear plasmid standard equivalent of 1.33×1014 vg/kg) and prednisone (1 mg/kg/day) 1 day pre- to 30 days post-gene delivery. The primary outcome measure is safety. The secondary outcome measures include micro-dystrophin expression quantified by western blot and immunofluorescence (sarcolemmal micro-dystrophin expression) in pre- and post-muscle biopsies (Week 12 post-infusion). Key efficacy outcome measures include change in the North Star Ambulatory Assessment (NSAA) and timed function tests (100m, 4-Stair Climb and Time to Rise).
Delandistrogene moxeparvovec has demonstrated an acceptable long-term safety profile 3 years post-treatment. Treatment-related adverse events (AEs) were mild to moderate, occurred mostly in the first 90 days of treatment, and all resolved. No serious AEs, study discontinuations, or AEs associated with clinically relevant complement activation were reported. All patients demonstrated a clinically meaningful improvement on NSAA (mean change [standard deviation] from baseline to Year 3: +7.5 points [3.42]). Patients treated with delandistrogene moxeparvovec generally maintained muscle strength (Time to Rise and 4-Stair Climb) and showed improvement in ambulation ability (100m) from baseline to Year 3.
Conclusions: The observed safety profile and the enduring response following gene transfer provides proof-of-concept for the continuation of clinical trials assessing delandistrogene moxeparvovec using single-dose gene transfer therapy in patients with DMD. We present the latest long-term (3-year) safety and functional data from this study.
This study is funded by Sarepta Therapeutics, Inc.