Aravindhan Veerapandiyan, MD
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News from REGENXBIO, which recently announced the initiation of patient recruitment for the Phase 1/2 AFFINITY DUCHENNE clinical trial (NCT05693142) of RGX-202, an investigational adeno-associated virus (AAV) vector-based gene therapy for Duchenne muscular dystrophy. DMD).1 Data collected from this trial may be used to identify potential participants in the AFFINITY DUCHENNE trial and potential future trials of RGX-202.
The open-label, multicenter AFFINITY DUCHENNE trial will initially recruit six ambulatory DMD patients aged 4 to 11 years. The patient will be divided into her two cohorts, each containing three of her patients, and the lower dose cohort will receive he 1×10.14 Genome copies (GC)/kg body weight, and a high-dose cohort receiving 2×1014 GC/kg body weight. The study may recruit an additional 9 patients later based on the results of an independent review of safety data.
Kenneth T. Mills, President and CEO of REGENXBIO, said:1 “The RGX-202 program is an important part of our ‘5x’25’ strategy to bring five AAV therapeutics to market or in late-stage development by 2025. Advances a highly differentiated product candidate developed with the potential to improve strength and motor function in boys with Duchenne. ”
RGX-202 uses REGENXBIO’s proprietary NAV AAV8 vector to deliver novel transgenes containing functional elements of the C-terminal (CT) domain found in native dystrophin.1 The company states that the presence of the CT domain “has been shown in preclinical studies to recruit several key proteins to the sarcolemmal membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice.” It is said that1
Participants in this trial must have a DMD gene mutation in exon 18 or greater, be able to walk 100 meters independently without assistive devices, and be able to complete the Rise Time test according to protocol-specific criteria . On a stable dose of systemic glucocorticoids according to standard of care for at least 12 weeks prior to Screening.
– Patients with detectable AAV8 total binding antibodies in serum, patients with left ventricular ejection fraction <55% at screening, patients with exon-skipping therapy for treatment of atallen or DMD 6 from study entry Patients who are unable to stop taking atallen or exon-skipping therapy within 3 months and 5 years from the time of RGX-202 administration will be excluded from the study. is subject to the discretion of
The primary endpoint of the study was the incidence of adverse events (AEs) and serious AEs. Secondary endpoints included changes in North Star Ambulatory Assessment raw and total scores, microdystrophin protein expression, and pharmacokinetic and vector release measures. Study participants will receive prophylactic immunosuppressive therapy aimed at reducing potential complement-mediated immune responses. The trial has started at the US site, with Canadian and European sites expected to open later.
“DMD is a devastating disease and there is still an unmet need for treatment,” said the principal investigator of the study and director of the Comprehensive Neuromuscular Program at the PPMD-accredited Duchenne Care Center, Muscular Dystrophy Association. Co-Director of Care Dr. Aravindhan Veerapandiyan said. Arkansas Children’s Hospital Center, added to statement.1 “Gene therapy such as RGX-202 may affect the progressive nature of Duchenne.”
The AFFINITY DUCHENNE trial was originally expected to start in the first half of 2022 following the approval of the Investigational New Drug Application for RGX-202 by the FDA in January 2022.2 However, the trial was postponed due to an “unexpected 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 launched AFFINITY BEYOND, an observational study evaluating the prevalence of AAV8 antibodies in male patients under the age of 12 with DMD.1