RARE Daily

Regenxbio Reports Positive Interim Data from 1/2 DMD Study

October 4, 2023

Rare Daily Staff

Regenxbio reported positive additional interim safety data and initial efficacy data from its phase 1/2 trial of RGX-202, its experimental treatment for the rare neuromuscular condition Duchenne muscular dystrophy.

Duchenne is a severe, progressive, degenerative muscle disease, affecting 1 in 3,500 to 5,000 boys born each year worldwide. Duchenne is caused by mutations in the Duchenne gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways. Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy, and premature death.

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. 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.

In a presentation at the 28th Annual International Congress of the World Muscle Society, the company presented interim data from the phase 1/2 AFFINITY DUCHENNE that showed RGX-202 was reported to be well tolerated with no drug-related serious adverse events in three patients, aged 4 to 11 years, dosed to date at dose level 1. Time of post-administration follow up ranges from three weeks to more than five months. The two patients who reached three-month follow-up have completed the immunosuppression regimen per study protocol.

Initial biomarker data from two patients who completed three-month trial assessments indicate encouraging increases in expression of RGX-202 microdystrophin from bicep muscle biopsies taken at three months following one-time administration of RGX-202. In addition, RGX-202 microdystrophin was detectable by immunofluorescence staining throughout muscle tissue at three months, with RGX-202 microdystrophin protein localized to the sarcolemma.

RGX-202 microdystrophin levels were measured using an automated and precise western blot method (Jess), and comparable results were confirmed with a proprietary liquid chromatography-mass spectrometry (LC-MS) method.

In the dose evaluation phase of the trial, four ambulatory, pediatric patients (ages 4 to 11 years old) are expected to enroll in two cohorts with different doses. After an independent safety data review for each cohort, a dose expansion phase of the trial may allow for up to seven additional patients to be enrolled at each dose level (for a total of up to nine patients in each dose cohort).

The company expects to share initial strength and functional assessment data for both dose levels in 2024. Additionally, Regenxbio expects to make a pivotal dose determination and initiate a pivotal program for RGX-202 in 2024.

“We plan to scale up production of RGX-202 using commercial-ready cGMP material from the Regenxbio Manufacturing Innovation Center to support a pivotal program in 2024, with a clear path to submit a BLA using the accelerated approval pathway, with RGX-202 microdystrophin as a surrogate endpoint for clinical benefit,” said Kenneth Mills, President and Chief Executive Officer of REGENXBIO. “This update firmly establishes RGX-202 as a key feature of our ‘5x’25’ vision to have five gene therapies either on the market or in late-stage development by 2025.”

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