One-year data from ENDEAVOR, a Phase 1b trial of delandistrogene moxeparvovec in patients with DMD


Clinical Trials

Poster Number: 107


Craig Zaidman, MD, Washington University School of Medicine and St Louis Children's Hospital, Crystal Proud, MD, Children's Hospital of The King's Daughters, Craig McDonald, MD, University of California Davis Health, Stefanie Mason, Sarepta Therapeutics, Inc., Maitea Guridi, F. Hoffmann-La Roche Ltd, Shufang Wang, Sarepta Therapeutics, Inc., Carol Reid, Roche Products Ltd, Eddie Darton, Sarepta Therapeutics, Inc., Christoph Wandel, F. Hoffmann-La Roche Ltd, Sarah Lewis, Sarepta Therapeutics, Inc., Jyoti Malhotra, Sarepta Therapeutics, Danielle Griffin, Sarepta Therapeutics, Inc., Rachael Potter, Sarepta Therapeutics, Inc., Louise Rodino-Klapac, PhD, Sarepta Therapeutics, Inc., Jerry Mendell, MD, Nationwide Children's Hospital

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 expression and safety of intended commercial process delandistrogene moxeparvovec material in ENDEAVOR (NCT04626674).

Methods: ENDEAVOR is a two-part, open-label, Phase 1b study with five cohorts of ambulatory and non-ambulatory patients across a broad age range and with varied DMD mutations. Cohort 1 (n=20) enrolled ambulatory ≥4- to <8-year-olds. Participants received a single intravenous 1.33x10^14 vg/kg (linear standard qPCR) dose of intended commercial process delandistrogene moxeparvovec material. The primary endpoint is change in SRP-9001 dystrophin protein expression from baseline to Week 12. Secondary endpoints include safety and change from baseline in SRP-9001 dystrophin expression as measured by immunofluorescence (IF) intensity and IF percent dystrophin-positive fibers. Exploratory endpoints include the North Star Ambulatory Assessment (NSAA) and timed function tests. A propensity-score-weighted external control (EC) cohort was employed to contextualize results. Results: We present safety, 1-year functional, and 12-week expression data from Cohort 1. SRP-9001 dystrophin expression corresponded with vector genome copies, confirming successful delivery of delandistrogene moxeparvovec to target cells. Safety of intended commercial process material was consistent with clinical process material. No new safety signals were identified. There was a clinically meaningful and statistically significant difference in least-squares mean change from baseline to Year 1 in NSAA total score (∆=3.2; P<0.0001), Time to Rise (∆=─1.2; P<0.0001), and 10-meter Walk/Run (∆=─1.0; P=0.0018) in treated patients relative to EC patients. Conclusions: Cohort 1 data suggest the safety and efficacy profile of intended commercial process delandistrogene moxeparvovec material is consistent with that of clinical process material, with no new safety signals identified, and robust SRP-9001 dystrophin expression and positive functional benefit observed. This study was sponsored by Sarepta Therapeutics and funded by Sarepta Therapeutics and F. Hoffmann-La Roche Ltd.