Pharmacy and Wellness Review
Abstract
Duchenne Muscular Dystrophy (DMD) is a severe muscle-wasting disease caused by dystrophin gene mutations. DMD occurs in one of 3,500 male live-born infants and has one of the highest prevalence of severe congenital myopathies. Two ongoing clinical trials have contributed to the United States (US) Food and Drug Administration’s (FDA) accelerated approval of Elevidys (delandistrogene moxeparvovec), a promising drug to treat DMD. Elevidys, a recombinant adeno-associated viral (rAA V) vector-based gene therapy, gained FDA approval based on findings from the ENDEA VOR trial (NCT04626674) and EMBARK trial (NCT05096221). The phase 1 ENDEA VOR trial focused on evaluating changes in dystrophin expression in ambulatory DMD patients ages two to 18. The trial's primary outcome measures assessed Elevidys' impact on dystrophin and micro-dystrophin protein expression, with secondary outcomes evaluating safety over 260 weeks. Elevidys demonstrated promising results in its open-label trial which led to accelerated approval.
The EMBARK trial, a phase 3, randomized, double-blind, placebo-controlled study, further investigates Elevidys. EMBARK assesses the therapy's impact on North Star Ambulatory Assessment (NSAA) scores and micro-dystrophin expression in DMD patients aged four to eight. Initial safety and functional data submitted to the FDA supported the accelerated approval, with ongoing assessments in various cohorts.
Gene therapies are known to have complex safety profiles, but recent successes, including Elevidys, indicate progress. Long-term safety studies are important to understand the overall safety profile and durability of gene therapies. Despite the high cost of gene therapies, Elevidys addresses unmet needs in a rare patient population.