A Phase 2 Clinical Trial Evaluating the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Patients with Duchenne Muscular Dystrophy (DMD) (S48.004) (2023)

<h3>Objective:</h3> To evaluate safety and efficacy of delandistrogene moxeparvovec (SRP-9001), compared with placebo, in patients with Duchenne muscular dystrophy (DMD) aged ≥4 to &lt;8 years. <h3>Background:</h3> Delandistrogene moxeparvovec is an investigational gene transfer therapy developed to address the root cause of DMD through targeted skeletal and cardiac muscle expression of SRP-9001 dystrophin, which contains key functional domains of dystrophin. <h3>Design/Methods:</h3> Study 102 (NCT03769116; N=41) is a Phase 2 study. Part 1 was a 48-week, randomized, double-blind, placebo-controlled period. In Part 2 (48 weeks), patients randomized to placebo in Part 1 received delandistrogene moxeparvovec. Part 3 is an ongoing, ≤212-week, open-label follow-up period. Full analyses from Parts 1 and 2 will be presented. <h3>Results:</h3> Overall maintenance of mean North Star Ambulatory Assessment (NSAA) score was observed 96 weeks after delandistrogene moxeparvovec treatment, when functional decline is expected based on natural history. Mean NSAA total score increased by 1.3 points at 48 weeks post-treatment in patients who received placebo in Part 1 and delandistrogene moxeparvovec in Part 2 (aged &gt;5 to &lt;9 years at dosing). In a post-hoc analysis, a statistically significant difference of 2 points in mean NSAA total score change from baseline was observed in patients treated in Part 2 versus the propensity-score-weighted external control group (<i>P</i>=0.0009). SRP-9001 dystrophin expression was achieved in all patients treated with delandistrogene moxeparvovec 12 weeks post-treatment. Patients treated in Part 1 continued to express SRP-9001 dystrophin 60 weeks post-treatment. The most common treatment-related treatment-emergent adverse events (AEs) were vomiting, decreased appetite and nausea. There were no discontinuations due to an AE and no deaths. No new safety signals have been observed in Study 102. <h3>Conclusions:</h3> Findings from Study 102 reinforce that delandistrogene moxeparvovec has a favorable benefit–risk profile, with no new safety signals observed. Overall maintenance of motor function was observed over 2 years following delandistrogene moxeparvovec treatment. <b>Disclosure:</b> 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 research support from Sarepta. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for PTC. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Grifols. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Shieh has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Avexis. Dr. Sahenk has nothing to disclose. Ms. Lehman has nothing to disclose. The institution of Ms. Lowes has received research support from Sarepta Therapeutics. Dr. Reash has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ATOM International. Dr. Reash has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Casimir, LLC. The institution of Dr. Reash has received research support from Sarepta. Dr. Reash has received intellectual property interests from a discovery or technology relating to health care. Dr. Reash has received intellectual property interests from a discovery or technology relating to health care. Dr. Iammarino has received personal compensation in the range of $0-$499 for serving as a Consultant for Genentech. Ms. Alfano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ATOM International, Ltd (Amicus Therapeutics, Catabasis, Genethon, Italfarmaco, NS Pharma, Pfizer, PTC Therapeutics). Ms. Alfano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta Therapeutics. The institution of Ms. Alfano has received research support from Novartis Gene Therapies. The institution of Ms. Alfano has received research support from Sarepta Therapeutics. The institution of Ms. Alfano has received research support from Audentes Therapeutics/Astellas Gene Therapies. Ms. Alfano has received intellectual property interests from a discovery or technology relating to health care. Dr. Sabo has nothing to disclose. Jeremy Woods has nothing to disclose. Christy Skura has nothing to disclose. Howard Mao has nothing to disclose. Loretta Staudt has nothing to disclose. Rachael Potter has received stock or an ownership interest from Sarepta Therapeutics. Ms. Griffin has stock in Sarepta Therapeutics. Ms. Griffin has received intellectual property interests from a discovery or technology relating to health care. Sarah Lewis has received stock or an ownership interest from Sarepta. Shufang Wang has received personal compensation for serving as an employee of Sarepta Therapeutics INC. Shufang Wang has received stock or an ownership interest from Sarepta Therapeutics INC. Tejdip Singh has received personal compensation for serving as an employee of Sarepta Therapeutics . Tejdip Singh has received stock or an ownership interest from 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.