REGENXBIO Announces FDA Clearance of IND for Clinical Trial of RGX-202, a Novel Gene Therapy Candidate for Duchenne Muscular Dystrophy


  • Potential one-time gene therapy for the treatment of Duchenne includes a novel, optimized microdystrophin transgene and REGENXBIO’s proprietary NAV® AAV8 vector
  • Innovative trial design, including comprehensive immunosuppressive regimen, to evaluate safety and optimal dose
  • cGMP process material made at commercial-scale to be used throughout clinical development of RGX-202
  • REGENXBIO expects to initiate trial in the first half of 2022

REGENXBIO Inc. (Nasdaq: RGNX) today announced the clearance of its Investigational New Drug (IND) application by the United States Food and Drug Administration (FDA) to evaluate RGX-202, a potential one-time gene therapy for the treatment of Duchenne muscular dystrophy (Duchenne) in a first-in-human clinical trial. RGX-202 is designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin. RGX-202 uses REGENXBIO’s proprietary NAV® AAV8 vector. REGENXBIO plans to initiate the trial in the first half of 2022.

“We are excited to advance RGX-202, our investigational gene therapy for patients with Duchenne, into the clinic. Additional therapeutic options are still needed for the treatment of Duchenne, and our trial design follows compelling evidence from preclinical studies which demonstrated that one-time treatment with RGX-202 can express meaningful levels of a novel, functional microdystrophin protein in muscle, and showed significant improvements in muscle force and function in animal models,” said Olivier Danos, Ph.D., Chief Scientific Officer of REGENXBIO. “This innovative AAV gene therapy candidate for Duchenne was developed in-house at REGENXBIO through a highly collaborative process between our expert research and manufacturing teams and we believe that RGX-202 can potentially address unmet needs for patients with Duchenne.”

The Phase I/II trial, named AFFINITY DUCHENNE, is a multicenter, open-label dose-escalation and dose-expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in patients with Duchenne. In the dose-escalation phase of the trial, six ambulatory, pediatric patients (ages 4 to 11 years old) with Duchenne are expected to enroll in two cohorts with doses of 1×1014 genome copies (GC)/kg body weight (n=3) and 2×1014 GC/kg body weight (n=3). After an independent safety data review for each cohort, a dose-expansion phase of the trial may allow for up to six additional patients to be enrolled at each dose level (for a total of up to nine patients in each dose cohort).

The trial design also consists of thorough safety measures informed by the Duchenne community and engagement with key opinion leaders, including a comprehensive, short-term, prophylactic immunosuppression regimen to proactively mitigate potential complement-mediated immunologic responses, and inclusion criteria based on dystrophin gene mutation status, including DMD gene mutations between exons 18 and 58. Trial endpoints include safety, immunogenicity assessments, pharmacodynamic and pharmacokinetic measures of RGX-202, including microdystrophin protein levels in muscle, and strength and functional assessments, including the North Star Ambulatory Assessment (NSAA) and timed function tests. Initial trial sites are expected to open in the U.S., with additional sites in Canada and Europe expected to follow.

“I am proud of our scientific and medical teams’ work with the Duchenne community resulting in a thoughtful and innovative clinical trial design, which we believe addresses a number of important factors, including safety considerations,” said Kenneth T. Mills, President and Chief Executive Officer of REGENXBIO. “This trial will use material derived from our proprietary commercial-scale process which is expected to enable consistent clinical supply and support the efficient transition to later-stage development. We are working quickly to start dosing patients in this trial and look forward to continuing our important work with stakeholders across the Duchenne community.”

In support of the IND application, RGX-202 cGMP-grade material has been produced at commercial-scale capacity (1,000L) using REGENXBIO’s proprietary suspension cell culture manufacturing process. REGENXBIO’s internal cGMP facility is designed to enable production in 2,000L bioreactors and is on track to be fully operational in the first half of 2022. REGENXBIO plans to manufacture RGX-202 at the new facility.

About RGX-202
RGX-202 is designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin. The presence of the CT domain 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. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase translational efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle-specific promoter (Spc5-12).

About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (Duchenne) is a rare genetic disorder, caused by mutations in the gene responsible for making dystrophin, a protein of central importance for muscle cell structure and function. Duchenne primarily affects males with approximately 1 in 3,500 to 1 in 5,000 males affected worldwide. The absence of functional dystrophin protein in individuals with Duchenne results in cell damage during muscle contraction, leading to cell death, inflammation, and fibrosis in muscle tissues. Initial symptoms of Duchenne include muscle weakness that is often noticeable at an early age, with diagnosis typically occurring by 5 years of age. Over time, individuals with Duchenne experience progressive muscle weakness and eventually lose the ability to walk. Respiratory and heart muscles are also affected, leading to difficulty breathing and the need for ventilator assistance, along with the development of cardiomyopathy. There is presently no cure for Duchenne.

REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. REGENXBIO’s NAV® Technology Platform, a proprietary adeno-associated virus (AAV) gene delivery platform, consists of exclusive rights to more than 100 novel AAV vectors, including AAV7, AAV8, AAV9 and AAVrh10. REGENXBIO and its third-party NAV Technology Platform Licensees are applying the NAV Technology Platform in the development of a broad pipeline of candidates in multiple therapeutic areas.

Tricia Truehart
Investor Relations and Corporate Communications
[email protected]

Brendan Burns, 212-600-1902
[email protected]

David Rosen, 212-600-1902
[email protected]