Long-term safety and sustained functional benefit in patients with DMD 4 years post-treatment with delandistrogene moxeparvovec in a Phase 1/2a study


Clinical Trials

Poster Number: 96


Jerry Mendell, MD, Center for Gene Therapy, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Colu, Zarife Sahenk, Center for Gene Therapy, Nationwide Children’s Hospital, Kelly Lehman, APN, Center for Gene Therapy, Nationwide Children’s Hospital, Linda Lowes, PT, PhD, Nationwide Children's Hospital, Natalie Reash, DPT, Nationwide Children's Hospital, Megan Iammarino, DPT, Nationwide Children's Hospital, Lindsay Alfano, PT, DPT, PCS, Nationwide Children’s, Sarah Lewis, Sarepta Therapeutics, Inc., Kathleen Church, MSW, CCRP, Center for Gene Therapy, Nationwide Children’s Hospital, Richard Shell, MD, Nationwide Children's Hospital, Rachael Potter, Sarepta Therapeutics, Inc., Danielle Griffin, Sarepta Therapeutics, Inc., Mark Hogan, Center for Gene Therapy, Nationwide Children’s Hospital, Shufang Wang, Sarepta Therapeutics, Inc., Stefanie Mason, Sarepta Therapeutics, Inc., Eddie Darton, Sarepta Therapeutics, Inc., Louise Rodino-Klapac, PhD, Sarepta Therapeutics, Inc.

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.