Gene transfer therapy safe, efficacious for children with Duchenne muscular dystrophy
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Key takeaways:
- Delandistrogene moxeparvovec demonstrated sustained improvement in function 4 years after treatment.
- Most adverse events occurred in the first 70 days of treatment, with no new safety events at 4 years.
Delandistrogene moxeparvovec improved motor function and was well-tolerated 4 years after treatment in a small cohort of children with Duchenne muscular dystrophy, according to a poster at the 2023 MDA Clinical & Scientific Conference.
“Delandistrogene moxeparvovec is an investigational gene transfer therapy developed to address the root cause of Duchenne muscular dystrophy through targeted skeletal and cardiac muscle expression of SRP-9001 dystrophin protein,” Jerry R. Mendell, MD, professor of pediatrics and neurology at Nationwide Children’s Hospital and The Ohio State University, and colleagues wrote.
Researchers evaluated the long-term safety and functional outcomes of delandistrogene moxeparvovec (SRP-9001, Sarepta Therapeutics) 4 years after treatment in a phase 1/2a, single-dose, open-label clinical trial.
They included four ambulatory patients with Duchenne muscular dystrophy, aged 4 to 8 years, who received an IV infusion of delandistrogene moxeparvovec (2.0×10^14 vg/kg) and prednisone (1 mg/kg per day) 1 day pretreatment to 30 days after treatment. Outcomes of interest included safety, dystrophin expression and change from baseline in North Star Ambulatory Assessment (NSAA) and timed function tests.
Researchers reported 72 adverse events, most of which occurred within the first 70 days of treatment, with 25% being treatment-related. No new safety events were reported 4 years after treatment. Further, delandistrogene moxeparvovec demonstrated improvement in function, with 5.3- and 5.5-point increases in NSAA at 90 days and 1 year, respectively. Researchers reported sustained stabilization of function 4 years following treatment, with a mean 7-point increase from baseline in NSAA. Similar trends were reported for timed function tests, including time to rise, four-stair climb, and 10 m and 100 m walk/run.
“Functional assessments demonstrated long-term, sustained, clinically meaningful improvement in motor function at ages where functional decline would be expected based on natural history,” Mendell and colleagues wrote.