Determine the safety, tolerability, and efficacy of RGX-202, an investigational, one-time AAV gene therapy designed to deliver an optimized microdystrophin gene to boys with Duchenne muscular dystrophy (DMD).

DMD is a severe, progressive, degenerative muscle disease caused by mutations in the DMD gene, encoding dystrophin, leading to muscle degeneration and weakness with loss of movement, required pulmonary and cardiac support, and premature death.  RGX-202 is the only gene therapy encoding a microdystrophin with the CT domain designed to improve function / preserve muscle health, delivered by the NAV® AAV8 vector, and manufactured using a process resulting in purity levels exceeding 80% full capsids. 

AFFINITY DUCHENNE® is a multicenter, open-label phase I/II/III trial.  The phase I/II portion (completely enrolled) included ambulatory boys with Duchenne 1-11 years old at screening who received RGX-202 at one of two dose levels [1x10¹⁴ (DL1) or 2x10¹⁴ (pivotal) genome copies/kg body weight].  The pivotal (phase III) portion of the study is currently enrolling ambulatory boys over 1 year of age with DMD.  AFFINITY DUCHENNE includes a prophylactic, short-course immune modulation designed to address known safety risks associated with high-dose AAV gene therapy.

Phase I/II interim as of May 7, 2025. RGX-202 has been well tolerated with no SAE, AESI, or liver injury (n=13).  Biomarker data demonstrated consistent, robust transduction and microdystrophin expression greater than the threshold of 10% compared to normal control [10.4% to 83.4% at DL1 (n = 3); 20.8% to 122.3% at pivotal (n=9)]. Furthermore, the motor function outcome measures of pivotal dose participants exceeded comparisons at 12 months using multiple methods: natural history external controls, cTAP predicted outcome, and MCID (n = 4).

At both dose levels, RGX-202 has been well tolerated; Robust RGX-202 microdystrophin expression and functional improvements were observed up to 12 months post-administration in boys 1-12 years old with DMD.