Abstract Details

SRP-9001 is an investigational gene transfer therapy developed for targeted expression of a shortened functional micro-dystrophin protein in skeletal and cardiac muscle.

This three-part, Phase 2 clinical trial (NCT03769116) evaluates the safety and efficacy of systemic gene transfer of rAAVrh74.MHCK7.micro-dystrophin (SRP-9001) in patients with Duchenne muscular dystrophy (DMD).

Part 1 is a 48-week, randomized, double-blind, placebo-controlled period. Part 2 is a 48-week period in which patients randomized to placebo in Part 1 receive SRP-9001. Part 3 is an open-label follow-up period (up to 212 weeks).

Participants (4–7-year-old ambulatory boys, confirmed DMD mutation between exons 18-58, stable steroid dosing) received SRP-9001 (n=20) or placebo (n=21). The intended dose was 2.0x10¹⁴ vg/kg (supercoiled qPCR, linear plasmid standard equivalent of 1.33x10¹⁴ vg/kg).

Randomization was stratified by age (4–5 and 6–7 years). Primary endpoints were change from baseline in micro-dystrophin expression (western blot; Week 12) and in North Star Ambulatory Assessment (Week 48). Safety endpoints included serious adverse events and treatment-emergent adverse events.

One-year functional results from Part 1 have been presented previously. Full analyses from Parts 1 and 2 will be presented, including 2-year functional and safety data from patients who received SRP-9001 in Part 1, 1-year functional and safety data from patients who received SRP-9001 in Part 2, expression for all patients 12 weeks post-SRP-9001 infusion and 60 weeks post-infusion for those dosed in Part 1.

Results suggest that SRP-9001 has a biological effect that may be clinically relevant in people with DMD. Results reinforce a potentially favorable benefit-risk profile.

This study was funded by Sarepta Therapeutics, Inc.