Expression of SRP-9001 dystrophin and stabilization of motor function up to 2 years post-treatment with delandistrogene moxeparvovec gene therapy in individuals with Duchenne muscular dystrophy

Introduction: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy designed for targeted expression of SRP-9001 dystrophin protein, a shortened retaining key functional domains the wild-type protein. Methods: This Phase 2, double-blind, two-part (48 weeks per part) crossover study (SRP-9001-102 [Study 102]; NCT03769116) evaluated delandistrogene in patients, aged ≥4 to <8 years with Duchenne muscular dystrophy. Primary endpoints (Part 1) were change from baseline (CFBL) (Week 12), by Western blot, and North Star Ambulatory Assessment (NSAA) score 48). Safety assessments included treatment-related adverse events (TRAEs). Patients randomized stratified age placebo (n = 21) or 20) crossed over Part 2. Results: was achieved all patients: mean CFBL Week 12 23.82% 39.64% normal Parts 1 respectively. In 1, 48 NSAA (least-squares mean, LSM [standard error]) +1.7 (0.6) treatment versus +0.9 placebo; p 0.37. Disparity motor function between groups likely confounded these results. 4- 5-year-olds matched function, scores significantly different (+2.5 points; 0.0172), but not 6-to-7-year-olds imbalanced (−0.7 0.5384). For patients treated +1.3 (2.7), whereas those maintained. As 2 exposed treatment, results compared propensity-score-weighted external control (EC) cohort. The difference group EC cohort statistically significant (+2.0 0.0009). most common TRAEs vomiting, decreased appetite, nausea. Most occurred within first 90 days resolved. Discussion: Results indicate robust overall stabilization up post-treatment. Differences population, because cohorts only age, other critical prognostic factors well at baseline.