Pivotal AFFINITY DUCHENNE results showed microdystrophin expression above the prespecified threshold in 93% of evaluable participants, with preliminary functional findings favoring treatment over external controls.
RGX-202, an investigational gene therapy for Duchenne muscular dystrophy (DMD), met the primary end point in the phase 3 portion of the multicenter, open-label AFFINITY DUCHENNE trial (NCT05693142), with mean microdystrophin expression exceeding 10% of normal levels at week 12. Interim functional findings from 9 participants who had reached 1 year of follow-up also showed outcomes favoring treatment over external controls.1
Presented at the 2026 Child Neurology Society (CNS) Annual Meeting, held October 14-17 in Montreal, Canada, findings from muscle biopsies available for 30 participants showed that RGX-202 achieved mean microdystrophin expression exceeding 10% of normal levels, meeting the study’s primary end point with statistical significance.¹ Led by Jahannaz Dastgir, DO, clinical development lead for the RGX-202 program at REGENXBIO, the analysis also found that 93% of evaluable participants achieved microdystrophin expression above this threshold (P < .0001).¹
The phase 3 cohort included 31 ambulatory boys aged 1 year and older who received a single intravenous infusion of RGX-202. Investigators used multiple validated methods to estimate expected disease progression in the absence of treatment.
At 1 year, participants treated with RGX-202 showed functional improvement and outcomes favoring external propensity score-weighted controls. Assessments included the North Star Ambulatory Assessment (NSAA) and timed function tests, including time to stand, 10-meter walk/run, and time to climb.1
Microdystrophin expression was also statistically significantly associated with functional improvement on the NSAA. According to the sponsor's announcement, week 12 expression correlated with change from baseline in NSAA at 1 year (P = .0002) and with NSAA change relative to the Collaborative Trajectory Analysis Project (cTAP) predictive model (P = .0005).2
RGX-202 was characterized as well tolerated in the phase 3 cohort. The most common drug-related adverse events (AEs) were vomiting (n = 19), fatigue (n = 11), and nausea (n = 10). Two drug-related serious AEs were reported, and both resolved without sequelae, according to the abstract.1
REGENXBIO identified the serious events as subacute myocarditis in an 8-year-old participant and asymptomatic liver injury in a 10-year-old participant. The company reported that the most recent cardiac MRI for the participant with myocarditis showed no fibrosis or change in ejection fraction. Among the 9 participants with 1-year follow-up, gamma-glutamyl transferase and total bilirubin levels did not exceed the upper limit of normal through that time point.2
RGX-202 is an investigational adeno-associated virus (AAV)-based gene therapy designed to deliver an optimized microdystrophin that includes the C-terminal (CT) domain of naturally occurring dystrophin. The pivotal dose used in the phase 3 cohort was 2 × 10¹⁴ genome copies per kilogram.1
