RGX-202 Gene Therapy Improves DMD Trajectory, Biomarkers

RGX-202, an investigational gene therapy for Duchenne muscular dystrophy (DMD), showed consistent evidence of efficacy based on functional and biomarker data in an interim analysis of the phase 1/2 AFFINITY DUCHENNE trial (NCT05693142), according to a press release from developer REGENXBIO.¹

Participants who received RGX-202 demonstrated functional improvement and better outcomes than controls for all measures. | Image Credit: Treecha- stock.adobe.com

Interim results among the first 5 participants in the dose level 2 (2x10¹⁴ GC/kg) cohort demonstrated consistent benefits at 9 and 12 months with RGX-202 vs natural history controls. Based on the patients’ age at dosing (approximately 6 to 12 years) and baseline functional status, 4 of 5 are expected to be experiencing decline in their disease trajectory, with results compared with strictly age- and baseline function–matched external natural history controls. Those who received RGX-202 showed improved North Star Ambulatory Assessment (NSAA) and timed function tests, including time to stand, 10-meter walk-run, and time to climb vs controls.

"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,” Steve Pakola, MD, chief medical officer of REGENXBIO, said 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 Application submission under accelerated approval in mid-2026."

Functional Outcomes With RGX-202 Gene Therapy

Participants who received RGX-202 demonstrated functional improvement and better outcomes than controls for all measures. The average improvement in NSAA among treated patients was 4 points from baseline and 4.8 points compared with natural history controls at 9 months after dosing. Results among 4 of 5 patients who reached 12 months post dosing were similar to results at 9 months, with improvement in all timed function tests vs baseline. Patients improved an average of 4.5 points from baseline in the NSAA and 6.8 points compared with natural history controls at 12 months post dosing.

Timed task velocity changes also exceeded minimal clinically important difference benchmarks at 12 months in the RGX-202 cohort.

Biomarkers Show Efficacy With RGX-202 Treatment

The primary end point in the pivotal phase of the AFFINITY DUCHENNE study is the proportion of participants whose RGX-202 microdystrophin expression is at least 10% at week 12, and biomarker data so far have shown consistent and high expression of RGX-202 microdystrophin. One patient who was 2 years old at dosing showed a microdystrophin expression level of 118.6% vs the natural history control.

Regarding safety, no serious adverse events (AEs) or AEs of special interest were reported. Nausea, vomiting, and fatigue, all typical with gene therapy administration, were the most common drug-related AEs. “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,” according to the news release.

"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," Aravindhan Veerapandiyan, MD, of Arkansas Children's Hospital, said 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 enthusiastic about the continued development of RGX-202 and the promise it holds for the Duchenne community."

Enrollment is still ongoing in the pivotal phase 3 portion of the AFFINITY DUCHENNE TRIAL, which aims to enroll approximately 30 participants.²

References

1. REGENXBIO reports new positive functional data from phase I/II AFFINITY DUCHENNE trial of RGX-202. News Release. REGENXBIO. June 5, 2025. Accessed June 12, 2025. https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-reports-new-positive-functional-data-phase-iii

2. AFFINITY DUCHENNE: RGX-202 gene therapy in participants with Duchenne muscular dystrophy (DMD). ClinicalTrials.gov. Updated May 13, 2025. Acced June 12, 2025. https://clinicaltrials.gov/study/NCT05693142