Gene Therapy RGX-202 Meets Primary End Point in Pivotal AFFINITY DUCHENNE Study, Supporting Accelerated Approval Plans

Positive topline data from the pivotal phase 1/2/3 AFFINITY DUCHENNE trial (NCT05693142) showed that investigational gene therapy RGX-202 met its primary end point with high statistical significance, prompting REGENXBIO to move toward discussions with the FDA regarding a potential accelerated approval pathway for Duchenne muscular dystrophy (DMD).¹

According to the company, REGENXBIO plans to pursue accelerated approval and is preparing for a potential commercial launch in 2027 following recent FDA discussions surrounding use of microdystrophin expression as a surrogate biomarker reasonably likely to predict clinical benefit. The agency reportedly indicated that externally controlled trials may be acceptable in certain situations where treatment effects are sufficiently robust enough to overcome limitations traditionally associated with external controls.¹

RGX-202 is an investigational adeno-associated virus serotype 8 (AAV8)-based gene therapy designed to deliver a differentiated microdystrophin transgene that includes a C-terminal domain intended to support muscle integrity and localization to the sarcolemma.² DMD is a rare X-linked neuromuscular disease caused by mutations in the dystrophin gene, resulting in progressive muscle degeneration, loss of ambulation, cardiomyopathy, respiratory decline, and shortened survival.³

The newly announced findings included interim data from the pivotal portion of AFFINITY DUCHENNE, which evaluated RGX-202 at a dose of 2x10¹⁴ genome copies/kg in 31 ambulatory boys aged at least 1 year. More than 20 additional participants have already enrolled in the confirmatory portion of the trial, with the company expecting all 60 patients across the pivotal and confirmatory cohorts to complete dosing by mid-2026.¹

At Week 12, 93% of participants achieved at least 10% microdystrophin expression, meeting the study’s primary end point with high statistical significance (P <.0001). Investigators also reported mean microdystrophin expression of 71.1% across all treated participants and 41.6% among boys older than 8 years. Furthermore, 80% of participants achieved greater than 40% microdystrophin expression.

Investigators also observed statistically significant correlations between microdystrophin expression and functional improvement at 1 year, including changes in North Star Ambulatory Assessment (NSAA) scores relative to baseline and predictive disease modeling.

“RGX-202 is the first gene therapy in development for Duchenne to demonstrate strong, statistically significant correlation between microdystrophin expression and functional improvement, a landmark distinction in the field,” Steve Pakola, MD, chief medical officer at REGENXBIO, said in a statement.¹

Interim functional findings from 9 participants aged approximately 5 to 12 years demonstrated statistically significant improvements across NSAA scores and timed function tests when compared with external natural history controls using propensity score weighting analyses.¹

These results build on previously reported findings presented at the 2026 Muscular Dystrophy Association Clinical & Scientific Conference, where investigators first reported encouraging changes in disease trajectory among boys treated with the pivotal dose.² At that time, treated participants demonstrated improvements exceeding expected natural history trajectories across NSAA and timed function tests.⁴

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At 12 months, participants treated with RGX-202 showed a 4.5-point improvement on NSAA relative to baseline and a 6.8-point improvement relative to external natural history cohorts. Investigators also reported robust biomarker findings, including microdystrophin expression changes of 120.5% among patients aged 1 to 3 years and continued evidence of sarcolemmal localization of the construct.⁴

“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,” principal investigator Aravindhan Veerapandiyan, MD, pediatric neuromuscular neurologist at Arkansas Children’s Hospital, said in a prior statement.⁴

Safety findings from the pivotal cohort remained generally favorable. According to REGENXBIO, RGX-202 was well tolerated overall, with 2 reported serious adverse events that resolved without sequelae.¹ One participant experienced subacute myocarditis, while another developed asymptomatic liver injury with elevated gamma-glutamyl transferase levels. Common treatment-related adverse events included nausea, vomiting, and fatigue, most of which were mild or moderate.

Importantly, investigators noted that markers associated with liver inflammation, including gamma-glutamyl transferase and bilirubin, remained below the upper limit of normal through 1-year post-treatment among evaluated participants in AFFINITY DUCHENNE.¹

The DMD gene therapy landscape has rapidly evolved over the last several years following the FDA approval of delandistrogene moxeparvovec (Elevidys; Sarepta Therapeutics), the first approved microdystrophin gene therapy for the disease.⁵ Continued regulatory discussions across the field have centered on the relationship between biomarker expression, functional outcomes, durability, and long-term safety.

REGENXBIO noted that it is currently finalizing plans for an ex-US study intended to support future global regulatory submissions.¹

REFERENCES
1. REGENXBIO. REGENXBIO reports positive topline and interim functional data from pivotal Phase III AFFINITY DUCHENNE trial of RGX-202. News release. May 14, 2026. Accessed May 2026. https://www.prnewswire.com/news-releases/regenxbio-announces-positive-topline-results-from-pivotal-phase-iii-affinity-duchenne-study-of-rgx-202-302771834.html
2. Tesi Rocha C, Veerapandiyan A, Iannaccone S, et al. RGX-202, an investigational gene therapy for the treatment of Duchenne muscular dystrophy: Interim phase I/II clinical data. Presented at: Muscular Dystrophy Association Clinical & Scientific Conference; March 8-11, 2026; Orlando, Florida.
3. National Institute of Neurological Disorders and Stroke. Muscular dystrophy. Updated March 25, 2025. Accessed May 14, 2026. https://www.ninds.nih.gov/health-information/disorders/muscular-dystrophy
4. REGENXBIO reports new positive functional data from phase 1/2 AFFINITY DUCHENNE trial of RGX-202. News release. June 5, 2025. Accessed May 14, 2026.
5. FDA approves first gene therapy for Duchenne muscular dystrophy. FDA news release. June 22, 2023. Accessed May 14, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-duchenne-muscular-dystrophy