RGX-202, an investigational gene therapy for the treatment of Duchenne Muscular Dystrophy: Interim clinical data

Topic:

Clinical Trials

Poster Number: O75

Author(s):

Carolina Tesi Rocha, MD, Stanford, Amy Harper, MD, VCU Health, Susan Iannaccone, MD, UT Southwestern, Nancy L. Kuntz, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Med, Aravindhan Veerapandiyan, MD, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, US, Steve Pakola, MD, REGENXBIO Inc., Dawn Phillips, PT, MS, PhD, REGENXBIO Inc., Catherine Wilson, DPT, MSPH, REGENXBIO Inc., Nidal Boulos, PhD, REGENXBIO Inc., Michelle Gilmor, PhD, REGENXBIO Inc. - Rockville, MD, Stacey Curtiss, PharmD, REGENXBIO Inc., Hiren Patel, PhD, REGENXBIO Inc., Michele Fiscella, PhD, REGENXBIO Inc., Paulo Falabella, MD, PhD, REGENXBIO Inc., Jahannaz Dastgir, DO, REGENXBIO Inc., Olivier Danos, PhD, REGENXBIO Inc.

OBJECTIVE: Present interim data for a phase I/II microdystrophin gene therapy clinical trial of RGX-202 in Duchenne muscular dystrophy.

BACKGROUND: Duchenne is a severe, progressive, degenerative muscle disease caused by mutations in the DMD gene which encodes for dystrophin, without which muscles degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy, and premature death.

RGX-202 is an investigational, one-time AAV gene therapy designed to deliver an optimized microdystrophin gene. RGX-202 is the only gene therapy that encodes for a novel microdystrophin protein that includes the C-Terminal (CT) domain found in naturally occurring dystrophin. In preclinical studies, the CT domain has been shown to protect muscles from contraction-induced stress and to improve muscle repair.

DESIGN/METHODS: The multicenter, open-label phase I/II AFFINITY DUCHENNE® trial is evaluating the safety, tolerability, and clinical efficacy of a one- time intravenous (IV) dose of RGX-202 at one of two dose levels (1×1014 or 2×1014 genome copies (GC)/kg body weight) in boys aged 1-11 years old with Duchenne.

RESULTS: As of July 8, 2024, RGX-202 has been well tolerated with no serious adverse events in boys aged 4-11 years old. Patients across both dose levels demonstrated robust RGX-202 microdystrophin expression three months following RGX-202 administration. RGX-202 microdystrophin ranged from 10.4% to 83.4% at dose level 1 (n = 3) and from 20.8% to 77.2% at dose level 2 (n=4). In the subset of boys at dose level 2 aged 8-11 years old (n = 3), RGX-202 microdystrophin ranged from 20.8 to 75.5%. Additionally, RGX-202 microdystrophin was localized to the sarcolemma. Pivotal study design and an updated interim data cut will be shared.

CONCLUSION: At both dose levels, RGX-202 has been well tolerated and demonstrated robust RGX-202 microdystrophin expression in boys with DMD 4-12 years of age.