A Phase 2 Clinical Trial Evaluating the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Patients with Duchenne Muscular Dystrophy (DMD)
Jerry Mendell1, Perry Shieh2, Zarife Sahenk1, Kelly Lehman1, Linda Lowes1, Natalie Reash1, Megan Iammarino1, Lindsay Alfano1, Brenna Sabo1, Jeremy Woods2, Christy Skura2, Howard Mao2, Loretta Staudt2, Rachael Potter3, Danielle Griffin3, Sarah Lewis3, Shufang Wang3, Tejdip Singh3, Louise Rodino-Klapac3
1Center for Gene Therapy, Nationwide Children’s Hospital, 2UCLA Medical Center, 3Sarepta Therapeutics, Inc.
Objective:
To evaluate safety and efficacy of delandistrogene moxeparvovec (SRP-9001), compared with placebo, in patients with Duchenne muscular dystrophy (DMD) aged ≥4 to <8 years.
Background:
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.
Design/Methods:
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.
Results:
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 >5 to <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 (P=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.
Conclusions:
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.