Functional improvements seen in patients after muscular dystrophy gene therapy

A novel gene therapy may improve the trajectories of patients with Duchenne muscular dystrophy (DMD), according to early clinical trial results.

As part of the Phase I/II AFFINITY DUCHENNE trial, five boys aged six to 12 years were treated with RGX-202, a single-dose gene therapy that aims to provide patients with a functional version of the microdystrophin gene. The five patients demonstrated improved physical performance, as well as increased microdystrophin expression. Additionally, no significant adverse side effects were observed, indicating that RGX-202 may drastically improve outcomes for patients with DMD.

'Today's findings support the potential of RGX-202 to positively change the disease course for Duchenne and meaningfully benefit patients living with this degenerative disease,' said Dr Steve Pakola, the chief medical officer of RegenXBio, who developed the therapy.

He added, 'The continued, positive data further strengthen our commitment to rapidly bring this potentially transformative therapy to market and support our planned biologics license application submission under accelerated approval in mid-2026.'

DMD is an inherited condition which leads to debilitating, degenerative muscle weakness. It is driven by a dysfunctional copy of the dystrophin gene, which is found on the X chromosome, making DMD more prevalent in boys. DMD affects one in 3500 to 5000 boys born worldwide each year.

RGX-202 uses the adeno-associated virus (AAV) as a vector to deliver a shortened, but functional, copy of the gene – known as microdystrophin – to reverse the effects of DMD. This gene demonstrated increased expression in patients following treatment, indicating that the gene construct has been actively taken up.

The functional benefits of RGX-202 were further validated using the North Star Ambulatory Assessment, a panel of physical function tests including time to stand, time to climb, and ten-metre walk-run, all of which were improved in patients following treatment.

'These findings suggest that microdystrophin expression observed with RGX-202 is leading to meaningful functional improvements, even in individuals with DMD who are expected to experience functional decline,' said Dr Aravindhan Veerapandiyan, a child neurologist at Arkansas Children's Hospital who was involved in the study. He added: 'It is both encouraging and essential to have innovative therapies that can help preserve muscle integrity and substantially delay disease progression.'

RegenXBio is recruiting participants for a follow-up Phase I/II/III trial, including younger children who have been shown to benefit from RGX-202, with two children aged two and three achieving relative microdystrophin expression of 118.6 and 122.3 percent respectively, relative to normal controls. Patients under four years old are currently not eligible for other microdystrophin-based gene therapies.

Future work will also aim to investigate the safety of RGX-202. This is especially pertinent following the death in March of a 16-year-old with DMD from acute liver failure after treatment with Elevidys, another single-dose AAV-based gene therapy delivering the microdystrophin gene (see BioNews 1282). Liver toxicity has been identified as a risk of gene therapies that use AAV vectors to deliver modified genes. Sarepta Therapeutics, the company producing Elevidys, provided a safety update after a second death was reported over the weekend.