RGX-202, An investigational gene therapy for the treatment of Duchenne muscular dystrophy: Interim Phase I/II clinical data

Topic:

Clinical Trials

Poster Number: 432 O

Author(s):

Carolina Tesi Rocha, MD, Stanford University, Aravindhan Veerapandiyan, MD, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, US, Susan T. Iannaccone, MD, UT Southwestern, Nancy Kuntz, MD, Ann & Robert H. Lurie Children's Hospital of Chicago, amy harper, MD, VCU Health, Nidal Boulos, PhD, REGENXBIO, Catherine Wilson, DPT, MSPH, REGENXBIO, Inc., Elisa Tsao, PhD, REGENXBIO, Inc., Michelle Gilmor, PhD, REGENXBIO, Stacey Curtiss, PharmD, REGENXBIO, Hiren Patel, PhD, REGENXBIO, Inc., Michele Fiscella, PhD, REGENXBIO, Inc., Olivier Danos, PhD, REGENXBIO Inc., Steve Pakola, MD, REGENXBIO, Inc., Jahannaz Dastgir, DO, Regenxbio

OBJECTIVE
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.

BACKGROUND
Duchenne 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.

DESIGN/METHODS
AFFINITY DUCHENNE® is a multicenter, open-label phase I/II/III trial of RGX-202 in ambulatory boys with Duchenne. The phase I/II portion (enrolled) included boys 1-11 years old at screening who received investigational RGX-202 at one of two dose levels [1×1014 (DL1) or 2×1014 (pivotal) genome copies/kg body weight]. The phase III/pivotal portion (enrolled) included boys over 1 year of age; confirmatory portion is currently enrolling boys over 1 year of age. AFFINITY DUCHENNE includes a novel, short-course immune modulation designed to address known safety risks associated with high-dose AAV gene therapy.

RESULTS
Phase I/II Interim Data (As of May 7, 2025): RGX-202 has been well tolerated with no SAEs or AESIs, including no liver injury (n=13). Biomarkers demonstrated consistent, robust transduction and microdystrophin expression greater than 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 via matched natural history external controls, cTAP predicted outcome, and MCID (n = 4).

CONCLUSIONS
At both dose levels, investigational RGX-202 has been well tolerated; in addition, robust RGX-202 microdystrophin expression and functional improvement were observed up to 12 months post-administration in boys 1-12 years old with Duchenne.