An investigational gene therapy, RGX-202, is showing promising results in the treatment of Duchenne muscular dystrophy (DMD). According to a press release, an interim analysis of the phase 1/2 AFFINITY DUCHENNE trial (NCT05693142) revealed consistent evidence of efficacy based on both functional and biomarker data.

The interim data, which included the first five participants in the dose level 2 cohort (2×10¹⁴ GC/kg), indicated consistent benefits at both 9 and 12 months following treatment with RGX-202, when compared to natural history controls. It was expected that four of the five participants, who where between 6 and 12 years old at the start of the trial, would experience a decline in their condition.However, those treated with RGX-202 showed improvements in the North Star Ambulatory Assessment (NSAA) and in timed function tests such as time to stand, 10-meter walk-run, and time to climb.

“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 Steve Pakola, MD, chief medical officer of REGENXBIO, in a statement.”At the same dose being used in the pivotal trial, RGX-202 participants exceeded natural history across all key measures, including the North Star Ambulatory Assessment, which is striking. we are particularly encouraged by the outperformance observed in older patients. The continued, positive data further strengthen our commitment to rapidly bring this potentially transformative therapy to market and support our planned Biologics License Request submission under accelerated approval in mid-2026.”

Functional Improvements Observed

The study revealed that participants treated with RGX-202 experienced functional improvements and better outcomes compared to the control group across all measured parameters. Treated patients showed an average improvement of 4 points from baseline in the NSAA, and a 4.8-point improvement compared to natural history controls, at 9 months post-dosing. Similar results were observed at 12 months post-dosing among four of the five patients,with improvements seen in all timed function tests compared to baseline. At 12 months, patients improved an average of 4.5 points from baseline in the NSAA and 6.8 points compared to natural history controls.

Changes in timed task velocity also surpassed the minimal clinically critically important difference benchmarks at 12 months in the RGX-202 cohort.

“Today’s findings support the potential of RGX-202 to positively change the disease course for Duchenne and meaningfully benefit patients.”

Biomarker Data Indicates Efficacy

The primary endpoint of the pivotal phase of the AFFINITY DUCHENNE study is the proportion of participants with at least 10% RGX-202 microdystrophin expression at week 12. The biomarker data collected thus far indicates consistent and high expression of RGX-202 microdystrophin. Notably, one patient who was two years old at the time of dosing exhibited a microdystrophin expression level of 118.6% compared to the natural history control.

In terms of safety, no serious adverse events (AEs) or AEs of special interest were reported. The most common drug-related AEs were nausea, vomiting, and fatigue, which are typical following gene therapy administration. According to the news release, “A proactive, short-course immune modulation regimen in combination with a differentiated construct and industry-leading product purity levels of more than 80% full capsids may contribute to a favorable safety profile for RGX-202.”

“These findings suggest that the 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 Aravindhan Veerapandiyan, MD, of Arkansas Children’s Hospital, in a statement. “These Phase 1/2 results, demonstrating functional improvements and favorable safety profile, underscore the potential of RGX-202 as a treatment option for individuals with DMD. It is both encouraging and essential to have innovative therapies that can help preserve muscle integrity and substantially delay disease progression. I’m eager about the continued advancement of RGX-202 and the promise it holds for the duchenne community.”

Enrollment is ongoing for the pivotal phase 3 portion of the AFFINITY DUCHENNE TRIAL, which aims to enroll approximately 30 participants.