Integrated Analyses of Data from Clinical Trials of Delandistrogene Moxeparvovec (SRP-9001) in Duchenne Muscular Dystrophy (DMD)
Crystal Proud1, Craig Zaidman2, Perry Shieh3, Craig McDonald4, John Day5, Stefanie Mason6, Maitea Guridi7, Lixin Han6, Lixi Yu6, Carol Reid8, Eddie Darton6, Christoph Wandel7, James Richardson6, Jyoti Malhotra6, Tejdip Singh6, Louise Rodino-Klapac6, Jerry Mendell9
1Children’s Hospital of the King’s Daughters, 2Department of Neurology, WUSTL, 3UCLA Medical Center, 4UC Davis Health, 5Department of Neurology, Stanford University, 6Sarepta Therapeutics, Inc., 7F. Hoffmann-La Roche Ltd, 8Roche Products Ltd, 9Center for Gene Therapy, Nationwide Children’s Hospital
Objective:
To evaluate functional data in patients with Duchenne muscular dystrophy (DMD) ≥4 to ≤8 years of age at 1 year following a single intravenous (IV) infusion of delandistrogene moxeparvovec (SRP-9001) versus a propensity-score-weighted external control (EC) cohort.
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 protein, which contains key functional domains of dystrophin.
Design/Methods:
Ambulatory patients with DMD ≥4 to ≤8 years of age received a single IV infusion of delandistrogene moxeparvovec (1.33x1014 vg/kg, linear standard qPCR).
The dataset included patients treated with clinical process delandistrogene moxeparvovec material (Study 101, Phase 1/2a; NCT03375164 and Study 102, Phase 2; NCT03769116) and intended commercial process delandistrogene moxeparvovec material (ENDEAVOR, Phase 1b; NCT04626674). Data were compared with a propensity-score-weighted EC cohort (N=131), comprised of natural history and external clinical trial data from three studies. The primary endpoint was 1-year change from baseline in North Star Ambulatory Assessment (NSAA) total score. Exploratory endpoints included effect on key timed function tests 1 year post-treatment. Collective safety data available from Study 101, Study 102 and ENDEAVOR are also presented.
Results:
The integrated analysis evaluated functional data from 52 patients, including patients from Study 101 (N=4), Study 102 (n=28) and Cohort 1 of ENDEAVOR (n=20). Results showed a statistically significant difference of 2.4 points (P<0.0001) in NSAA change from baseline to Year 1 in treated patients versus the EC cohort (n=105). In a collective safety analysis from the three studies, there were no adverse events that led to study discontinuation and no deaths.
Conclusions:
Delandistrogene moxeparvovec demonstrated a clinically meaningful and statistically significant difference in NSAA versus a propensity-score-weighted EC cohort at Year 1, suggesting a beneficial modification of the DMD disease trajectory. Collective safety data were consistent and manageable across studies.