Early Insights on 3 Patients With DMD From Trial Assessing Gene Therapy RGX-202: Aravindhan Veerapandiyan, MD

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“I know it's very early days with only 3 patients dosed so far, but the dystrophin expression and where it is expressed in the muscle membrane—where we want to see [it]—it's all encouraging. I'm hoping that we'll continue to follow these boys to see how this translates into clinical improvement. For the future, I think we are planning to move on to the high-dose cohort or cohort 2 since the safety data from this first cohort of patients with this dosing has been very encouraging.”

REGENXBIO’s RGX-202, an investigational adeno-associated virus (AAV) vector-based gene therapy for Duchenne muscular dystrophy (DMD), uses the company’s proprietary NAV AAV8 vector, and is intended to deliver a novel transgene which contains the functional elements of the C-Terminal (CT) domain seen in natural dystrophin. The company noted in a recent announcement that the CT domain's presence recruited several key proteins to the muscle cell membrane in the preclinical studies, which led to improved muscle resistance to contraction-induced muscle damage in dystrophic mice.¹

Additional findings from the ongoing phase 1/2 AFFINITY DUCHENNE trial (NCT05693142) of RGX-202 showed a reduction in key DMD measures among pediatric patients treated with the agent.1 Presented at the 2023 Annual International Congress of the World Muscle Society, the therapy reported to be well tolerated with no therapeutic-related serious adverse effects in 3 patients, aged 4.4, 10.6, and 6.3 years, dosed at the level 1 dosage. The time of post administration follow-up ranged from 3 weeks to more than 5 months and the 2 patients who reached a 3-month follow-up completed the immunosuppression regimen.

Following the news, Aravindhan Veerapandiyan, MD, pediatric neuromuscular neurologist at Arkansas Children's Hospital and associate professor of pediatrics at the University of Arkansas for Medical Sciences, sat down in an interview with NeurologyLive® to provide an overview of the research. He talked about the 3 patients involved in the microdystrophin gene transfer clinical trial, and how the gene therapy has impacted dystrophin expression and serum creatinine kinase levels in the treated patients. In addition, he explained the unique features in the gene construct that make this study stand out, and how it might impact future clinical outcomes.

REFERENCES
1. REGENXBIO Presents Interim Clinical Data from Phase I/II AFFINITY DUCHENNE™ Trial of RGX-202 at 28th Annual International Congress of the World Muscle Society. News Release. REGENXBIO. Published October 3, 2023. Accessed October 16, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-presents-interim-clinical-data-phase-iii-affinity