REGENXBIO Reports Positive Phase 1/2 Data for Higher Dose of RGX-202 in Duchenne Muscular Dystrophy

Steve Pakola, MD

Newly announced data from level 2 the phase 1/2 AFFINITY DUCHENNE trial (NCT05693142) showed that treatment with higher doses of RGX-202 (REGENXBIO), an investigational gene therapy, led to positive changes in disease trajectory and improvements in certain biomarkers among patients with Duchenne muscular dystrophy (DMD).¹

AFFINITY DUCHENNE, which began in 2023, includes 2 cohorts of patients, with the lower-dose cohort receiving 1x10¹⁴ genome copies (GC)/kg body weight and the higher-dose cohort receiving 2x10¹⁴ GC/body weight. Using a cut-off date of May 7, 2025, the latest data update included 5 patients, aged 6-12 years at dosing, who were in receiving higher doses of RGX-202.

Relative to natural history cohorts, those on the gene therapy showed improvements across a variety of scales, including North Star Ambulatory Assessment (NSAA) and timed function tests (Time to Stand, 10 Meter Walk-run, Time to Climb). At 9 months, RGX-202-treated patients demonstrated an average improvement of 4 points on NSAA relative to baseline and a 4.8-point difference compared with natural history cohorts. Notably, dose level 2 participants’ timed task velocity changes exceeded minimal clinically important difference (MCID) benchmarks at 12 months.

"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. 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," Steve Pakola, MD, chief medical officer at REGENXBIO, said in a statement.¹

He added, "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."

While 4 of 5 participants reached 12 months of RGX-202 dosing, all patients at that time point demonstrated data that was similar to 9-month findings. At 12 months, treated patients continued to show improved performance on timed function tests and NSAA, exceeding external natural history controls. On NSAA, patients treated with the gene therapy demonstrated a 4.5-point improvement on NSAA relative to baseline and a 6.8-point improvement relative to natural history.

In terms of biomarker data, the therapy continued to show a pronounced effect on microdystrophin expression, as well as VCN copies/nucleus, and positive fiber percentage. Within the dose level 2 group, investigators reported microdystrophin expression change of 120.5% in patients aged 1-3 (n = 2) compared with control. Investigators also reported microdystrophin expression changes of 54.3% and 39.7% in the 4-7 (n = 2) and 8-11 (n = 5) age groups.

READ MORE: Reactivating Muscle Stem Cells in DMD: The Science Behind SAT-3247

REGENEXBIO noted that RGX-202 was appropriately localized to the sarcolemma, demonstrating that the differentiated construct with the inclusion of the C-terminal (CT) domain is appropriately targeting the muscle. Furthermore, the gene therapy continued to show the highest reported vector genome copies (4.9-55.4) measured by qPCR across approved or investigational gene therapies.

Aravindhan Veerapandiyan, MD

"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, a pediatric neuromuscular neurologist at Arkansas Children’s Hospital and associate professor of pediatrics at the University of Arkansas for Medical Sciences, said in a statement.¹ "These Phase I/II 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."

Safety, a concern typically for gene therapies, was not an issue for RGX-202, as the agent was well tolerated with no serious adverse events (AEs) or AEs of special interest. Some of the common AEs observed were nausea, vomiting, and fatigue, which were typical for gene therapy administration. Investigators noted that the proactive, short-course immune modulation regimen in combination with a differentiated construct and industry-leading product purity levels or more than 80% full capsids may have contributed to the encouraging safety profile of RGX-202.

REFERENCE
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 5, 2025. https://www.prnewswire.com/news-releases/regenxbio-reports-new-positive-functional-data-from-phase-iii-affinity-duchenne-trial-of-rgx-202-302473842.html