REGENXBIO steps closer to approval for Duchenne gene therapy

REGENXBIO announced positive interim safety and efficacy data from its Phase I/II AFFINITY DUCHENNE clinical trial for an investigational therapeutic used to treat Duchenne muscular dystrophy in children. The company’s RGX-202 is a gene therapy designed to deliver a novel microdystrophin gene that includes key regions of the naturally occurring dystrophin gene.

In patients aged 5.8 and 8.5 who received RGX-202 at dose level two, RGX-202 microdystrophin expression was measured to be 77.2%, and 46.5%, respectively, compared to control after three months.

Craig Malzahn, SVP technical operations at REGENXBIO, told BioProcess Insider, “one-time administration of RGX-202 aims to address the underlying cause of Duchenne by potentially enabling production of microdystrophin in muscle cells to protect them from damage and ultimately preserve muscle function.”

Duchenne muscular dystrophy is a genetic disorder characterized by a mutation in the dystrophin gene. It causes severe muscle fiber degeneration, predominantly in boys, that restricts their mobility and confines them to wheelchairs, leading to early death.

“I remain encouraged by the biomarker data from the AFFINITY DUCHENNE trial of RGX-202 and am eagerly anticipating the initial functional data from this program,” said Aravindhan Veerapandiyan, child neurologist and assistant professor at Arkansas Children's Hospital. “This update is also encouraging for the Duchenne community, which is exploring various treatment options that could influence disease progression.”

Veerapandiyan has performed clinical research on Duchenne muscular dystrophy and other neuromuscular disorders in children. He authored a 2020 paper focused on caring for patients with muscular dystrophies in light of complications presented by the COVID-19 pandemic.

“We are seeing a clear dose response and consistent, robust microdystrophin expression levels across all treated patients in the AFFINITY DUCHENNE trial, and, notably, among the highest levels of microdystrophin expression reported in older ambulatory patients,” said Curran Simpson, president and CEO of REGENXBIO. “This data continues to build on the totality of evidence supporting the potential for RGX-202 to be a differentiated, best-in-class treatment for Duchenne.”

Malzahn said that the company manufactures RGX-202 in house at its Manufacturing Innovation Center, located at the company’s headquarters in Rockville, Maryland, using the company’s proprietary NAVXpress suspension-based manufacturing process.

“The NAVXpress platform has demonstrated robust scalability with consistent yield and product purity,” Malzahn said. “REGENXBIO has the capacity and yields to produce 2,500 doses of RGX-202 per year.”

He added that the innovation center is a current good manufacturing practice (CGMP) gene-therapy facility that is designed and built for manufacturing REGENXBIO’s NAV-technology–based adeno-associated viral (AAV) vectors. Manufacturing can scale up to 2,000 L, making it suitable for commercial production.

“RGX-202 is a differentiated product candidate utilizing an advanced microdystrophin construct with potential for improved functional benefit, as shown in our preclinical data,” Malzahn said. “It is the only microdystrophin product approved or in development that includes the C-Terminal domain, a key region of the naturally occurring dystrophin gene, which has been shown in preclinical studies to protect the muscle from contraction-induced stress and improve its ability to repair itself.”

“We are very excited about the data to date in the AFFINITY DUCHENNE trial of RGX-202, which has demonstrated consistent high expression of microdystrophin across treated patients in all age groups.”