REGENXBIO DMD Gene Therapy Trial Delayed Due to Manufacturing Issue


The trial was set to begin patient dosing in the first half of this year.

During its Q1 earnings call, REGENXBIO disclosed that it uncovered an “unexpected and isolated observation” during the vial-filling stage of the manufacturing process for its Duchenne muscular dystrophy gene therapy at a third-party manufacturing facility.1

The discovery will disrupt the initiation of patient dosing in the first in human phase 1/2 AFFINITY DUCHENNE clinical trial of RGX-202. The gene therapy, which utilizes the company’s proprietary NAV AAV8 vector to deliver a novel microdystrophin transgene that includes the functional elements of the C-Terminal domain found in naturally occurring dystrophin, has demonstrated evidence of microdystrophin protein expression in muscles in preclinical studies.

“Though we made the difficult decision to delay dosing patients in our RGX-202 trial, we continue to prepare for trial initiation,” Kenneth T. Mills, president and chief executive officer of REGENXBIO, said in a statement.1

Following its investigational new drug application approval in January 2022,2 the company planned to initiate the trial in the first half of this year. Now, due to the manufacturing issue, REGENXBIO says that dosing will likely take place in early 2023.

The unfortunate discovery comes as the company also announced that its in-house manufacturing facility—which it intended to use for future manufacturing of RGX-202—is now operational and allows for the high-yield production of NAV vectors at up to 2000 liters using the company’s platform suspension cell culture process.

The phase 1/2 AFFINITY DUCHENNE trial is a multicenter, open-label, dose escalation and dose expansion study set to evaluate the safety, tolerability, and efficacy of a one-time intravenous dose of RGX-202 in patients with Duchenne muscular dystrophy.

The trial plans to enroll 6 ambulatory pediatric patients in 2 dosing cohorts: 1x1014 genome copies (GC)/kg body weight (n=3) and 2x1014 GC/kg body weight (n=3). Up to 6 additional patients may be added in each cohort during the dose expansion phase pending review by an independent safety data monitoring board. Safety measures, including inclusion criteria that includes patients with DMD gene mutations between exons 18 and 58 and a short-term immunosuppression regimen in order to mitigate risk of immunologic response, will be employed.

Trial end points include safety, microdystrophin protein levels in muscle, immunogenicity assessments, and strength and functional assessments, including the North Star Ambulatory Assessment and timed function tests.

1. REGENXBIO reports first quarter 2022 financial results and recent operational highlights. News release. REGENXBIO. May 4, 2022.
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.
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