Michael Kelly, PhD, on Potential of Nonviral Approaches to DMD Gene Therapy

"Non-AAV viruses are an important way of where the field is moving today. And that allows us to get away from not just the neutralizing antibodies, but ways to deal with redosing that we think it's going to be a concern over the next few years and ways to deal with the limitations that we've got with size of products that have been carried. We've funded heavily a number of organizations that are using non-viral approaches to try and deliver things and it's still in its early stages, but it's promising results. And we feel that if this is successful, it could really topple some of the challenges that we've dealt with:gene size, redosing, and getting them to younger patients.”

While patients with Duchenne muscular dystrophy (DMD) enjoyed the breakthrough approval of delandistrogene moxeparvovec (Elevidys) gene therapy in 2023, there remain questions to be answered and more research to be done, with DMD and with current challenges with adeno-associated virus (AAV) gene therapy in general. Concerns with durability and efficacy also arose when Sarepta announced that he global, pivotal, phase 3 EMBARK study (Study SRP-9001-301; NCT05096221) that supported Elevidys’ approval had failed its primary end point.

CGTLive spoke with Michael Kelly, PhD, chief scientific officer, CureDuchenne, to learn more about the potential of non-viral gene therapy in treating DMD and other muscular dystrophies. He stressed how this mode of gene therapy could help address current challenges with viral gene therapy, including gene delivery size limitations and redosability.

REFERENCE

Sarepta Therapeutics announces topline results from EMBARK, a global pivotal study of ELEVIDYS gene therapy for Duchenne muscular dystrophy. News release. Sarepta Therapeutics. October 30, 2023. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-topline-results-embark-global-0