DMD Gene Therapy Candidate RGX-202 Earns Orphan Drug Status

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by Steve Bryson, PhD |

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RGX-202, a one-time experimental gene therapy for the treatment of Duchenne muscular dystrophy (DMD), has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA).

The designation is given to investigational therapies to treat rare medical conditions or diseases that affect fewer than 200,000 people in the U.S.

Orphan drug status provides benefits to support the process of developing new therapeutics, including tax credits for costs associated with clinical trials, exemptions from certain fees, and marketing exclusivity for seven years if the therapy achieves FDA approval.

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According to the gene therapy’s developer, Regenxbio, RGX-202 is in the preclinical phase of development and the company is currently completing an application that will ask the FDA for permission to begin the first clinical trial by the end of the year.

“This important designation is a milestone in the development of RGX-202 and highlights the need for potential new treatment options for patients with Duchenne,” Olivier Danos, PhD, chief scientific officer of Regenxbio, said in a press release.

DMD is characterized by a lack of dystrophin protein due to mutations in the encoding DMD gene. Without dystrophin, muscles degenerate and weaken, including skeletal muscles attached to bones and muscles of the heart and lungs.

RGX-202 contains a transgene that provides instructions to make a shortened, yet functional, version of the dystrophin protein called microdystrophin. The transgene is delivered to muscle cells using Regenxbio’s propriety NAV adeno-associated virus (AAV) gene delivery platform. AAV vectors are used commonly in gene therapy as they are safe and relatively easy to manipulate in the laboratory.

RGX-202 also contains gene coding regions that retain selected elements of naturally occurring dystrophin, including an extended region of the protein’s C-Terminal (CT) domain. In a muscular dystrophy mouse model, the presence of the CT domain recruited several key proteins to the membrane of muscle cells, which helped to resist contraction-induced muscle damage.

The therapy also has features designed to improve gene expression (activity), increase microdystrophin protein production, and reduce immune responses. In addition, RGX-202 utilizes a well-characterized muscle-specific gene promoter to direct microdystrophin production in skeletal and heart muscles.

The one-time administration of the gene therapy aims to treat the underlying cause of DMD — regardless of genetic mutation — to protect muscles from damage and preserve muscle function.

“We look forward to advancing this one-time gene therapy into the clinic,” added Danos.

Commercial-scale production has begun using Regenxbio’s cell culture manufacturing process, and the company’s internal facility is expected to generate up to 2,000 liters for RGX-202 clinical development.