Duchenne Muscular Dystrophy Gene Therapy Trial Begins Recruiting Patients


REGENXBIO has also initiated recruitment for AFFINITY BEYOND, an observational study assessing the prevalence of AAV8 antibodies in male patients with DMD.

The phase 1/2 AFFINITY DUCHENNE clinical trial (NCT05693142) for REGENXBIO’s RGX-202, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Duchenne muscular dystrophy (DMD), has begun recruiting patients.1

The initiation of the AFFINITY DUCHENNE trial was originally expected to being in the first half of 2022, following the FDA’s clearance of RGX-202's investigational new drug application in January of that year.2 However, the trial was delayed due to an “unexpected and isolated observation” that occurred during the vial-filling stage of the manufacturing process at a third-party manufacturing facility.3 Alongside AFFINITY DUCHENNE, REGENXBIO has also initiated recruitment for AFFINITY BEYOND, an observational study assessing the prevalence of AAV8 antibodies in male patients under the age of 12 years with DMD.1 The trial may help to identify patients for enrollment in AFFINITY DUCHENNE.

"I am pleased that we are now able to initiate the trial for RGX-202 and also begin enrollment activities in our AAV8 antibody screening study," Kenneth T. Mills, president and chief executive officer, REGENXBIO, said in a statement.1 "The RGX-202 program is a key piece of our '5x'25' strategy to have 5 AAV therapeutics either on the market or in late-stage development by 2025. We look forward to continuing to work closely with the Duchenne community as we advance a highly differentiated product candidate developed with the potential to improve muscle strength and motor function in boys with Duchenne."

RGX-202 uses REGENXBIO’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.1 The company has noted that the CT domain's presence “has been shown in preclinical studies to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice.”1 

The multicenter, open-label AFFINITY DUCHENNE trial will initially seek to recruit 6 patients with DMD who are ambulatory and aged 4 to 11 years. The patients will be divided into 2 cohorts including 3 patients each, with the lower-dose cohort receiving 1x1014 genome copies (GC)/kg body weight and the higher-dose cohort receiving 2x1014 GC/kg body weight. The study may later recruit an additional 9 patients based on the results of an independent safety data review.

Participants in the trial will be required to have a DMD gene mutation in exons 18 and above, must be able to walk 100 meters independently without assistive devices, must be able to complete the Time to Stand Test per protocol-specific criteria, and must be on a stable dose of systemic glucocorticoids according to the standard of care for at least 12 weeks prior to screening. Patients with detectable AAV8 total binding antibodies in serum, those with a left ventricular ejection fraction on screening of less than 55%, those who have received ataluren or an exon-skipping therapy for the treatment of DMD within 6 months of entry into the study, and those who are unable to cease taking ataluren or exon-skipping therapy for 5 years from the time of RGX-202's administration will be excluded from the study. Additional exclusion criteria relate to patient health status, treatment-history, and investigator discretion. 

The study’s primary end point is the incidence of adverse events (AE) and serious AEs. Secondary end points include changes in North Star Ambulatory Assessment raw and total score, microdystrophin protein expression, and measures of pharmacokinetics and vector shedding. Participants in the trial will receive a prophylactic immunosuppression regimen intended to mitigate potential complement-mediated immune responses. The trial will begin at sites in the United States, with sites in Canada and Europe expected to open later on.

"DMD is a devastating disease and there are still unmet therapeutic needs," Aravindhan Veerapandiyan, MD, a principal investigator in the study and director of the Comprehensive Neuromuscular Program, PPMD Certified Duchenne Care Center, and co-director of the Muscular Dystrophy Association Care Center at Arkansas Children's Hospital, added to the statement.1 "Gene therapies, like RGX-202, have the potential to impact the progressive nature of Duchenne."

1. REGENXBIO announces phase I/II trial of RGX-202, a novel gene therapy candidate for Duchenne muscular dystrophy, is active and recruiting patients. News release. REGENXBIO Inc. January 23, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-phase-iii-trial-rgx-202-novel-gene-therapy 
2. REGENXBIO announces FDA clearance of IND for clinical trial of RGX-202, a novel gene therapy candidate for Duchenne muscular dystrophy. News release. REGENXBIO. January 6, 2022. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-fda-clearance-ind-clinical-trial-rgx-202 
3. REGENXBIO reports first quarter 2022 financial results and recent operational highlights. News release. REGENXBIO. May 4, 2022. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-reports-first-quarter-2022-financial-results-and 
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