Abstract Details

Title One-year Data from ENDEAVOR, a Phase 1b Trial of Delandistrogene Moxeparvovec (SRP-9001) in Patients with Duchenne Muscular Dystrophy (DMD)

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S48 - Therapeutics for Muscle Disease (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Objective To evaluate expression and safety of intended commercial process delandistrogene moxeparvovec (SRP-9001) material in ENDEAVOR (NCT04626674).

Background 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.

Design/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 1.33x10¹⁴ 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.

Authors/Disclosures
Craig M. Zaidman, MD (Washington University in St Louis) PRESENTER	Dr. Zaidman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for sarepta. The institution of Dr. Zaidman has received research support from Washington University in St Louis. The institution of Dr. Zaidman has received research support from Novartis.
Crystal M. Proud, MD (CSG Child & Adolescent Neurology)	Dr. Proud has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Avexis. Dr. Proud has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Proud has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sarepta. Dr. Proud has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Avexis. Dr. Proud has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Proud has received research support from Biogen. The institution of Dr. Proud has received research support from Sarepta. The institution of Dr. Proud has received research support from Avexis. The institution of Dr. Proud has received research support from PTC. The institution of Dr. Proud has received research support from CSL Behring. The institution of Dr. Proud has received research support from Scholar Rock. The institution of Dr. Proud has received research support from Catabasis.
Craig McDonald, MD (UC Davis Dept. of PM&R)	Dr. McDonald has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PTC Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Solid Biosciences. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Solid Biosciences. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edgewise Therapeutics. The institution of Dr. McDonald has received research support from Sarepta Therapeutics. The institution of Dr. McDonald has received research support from PTC Therapeutics. The institution of Dr. McDonald has received research support from Edgewise Therapeutics. The institution of Dr. McDonald has received research support from Capricor Therapeutics. The institution of Dr. McDonald has received research support from Italfarmaco. Dr. McDonald has received research support from NS Pharma. The institution of Dr. McDonald has received research support from NIH (NINDS). The institution of Dr. McDonald has received research support from Parent Project Muscular Dystrophy. The institution of Dr. McDonald has received research support from Muscular Dystrophy Association. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Member National Advisory Board for Medical Rehabilitation Research with NIH.
Stefanie Mason, MD	Dr. Mason has received personal compensation for serving as an employee of Sarepta. Dr. Mason has stock in Sarepta. An immediate family member of Dr. Mason has stock in Sarepta. The institution of an immediate family member of Dr. Mason has received research support from Biogen. The institution of Dr. Mason has received research support from NIH. The institution of Dr. Mason has received research support from Chest Foundation.
	No disclosure on file
Shufang Wang	No disclosure on file
	No disclosure on file
Eddie Darton (Sarepta Therapeutics)	No disclosure on file
Christoph Wandel, MD, PhD	Christoph Wandel, MD, PhD has received personal compensation for serving as an employee of F Hoffmann-LaRoche AG. Christoph Wandel, MD, PhD has stock in F Hoffmann-La Roceh AG, Basel, CH; Bayer AG, Leverkusen, FRG.
	No disclosure on file
	No disclosure on file
Danielle A. Griffin	Ms. Griffin has stock in Sarepta Therapeutics. Ms. Griffin has received intellectual property interests from a discovery or technology relating to health care.
Rachael Potter	No disclosure on file
Louise R. Rodino-Klapac (Sarepta Therapeutics)	Ms. Rodino-Klapac has received personal compensation for serving as an employee of Sarepta Therapeutics, Inc.. Ms. Rodino-Klapac has received stock or an ownership interest from Sarepta Therapeutics. Ms. Rodino-Klapac has received intellectual property interests from a discovery or technology relating to health care.
Jerry R. Mendell, MD, FAAN (The Research Institute at Nationwide Children's Hospital)	Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vertex. Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta Therapeutics . The institution of Dr. Mendell has received research support from Sarepta.

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