RegenxBio Reports Positive Initial Efficacy Data from DMD Gene Therapy Trial

Rare Daily Staff

RegenxBio reported additional interim safety and efficacy data from its phase 1/2 AFFINITY DUCHENNE trial of its experimental gene therapy RGX-202 in children with Duchenne muscular dystrophy 4 to 11 years old showed initial evidence of strength and functional improvement.

“RGX-202 at dose level 2 is demonstrating significantly increased microdystrophin expression in a 12-year-old patient,” said Kenneth Mills, president and CEO of RegenexBio. “We know there is an insufficient level of data available to the community for boys older than 7 years, and we are committed to being transparent with our data for a Duchenne community in need of new treatment options that can meaningfully impact disease. In addition, we are encouraged by the safety data at both dose levels and initial caregiver observations of strength and motor function improvement in boys treated with RGX-202.”

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 has differentiated and important biology most similar to naturally occurring dystrophin that protects from the muscle degradation associated with Duchenne.

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. 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.

The phase 1/2 AFFINITY DUCHENNE trial 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 dose of RGX-202 in patients with Duchenne. In the dose evaluation phase of the trial, four ambulatory, pediatric patients are expected to enroll in two cohorts with two, weight-based dose levels. After an independent safety data review for each cohort, a dose expansion phase of the trial may allow for additional patients to be enrolled.

The trial design was 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 in exons 18 and above. 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 and timed function tests.

As of February 28, 2024, RGX-202 has been well tolerated with no drug-related serious adverse events in five patients at the two dose levels. Time of post-administration follow up ranges from approximately seven weeks to over eleven months. All patients who reached three-month follow-up have completed the immunosuppression regimen per study protocol.

In new data from the first patient, aged 12.1 years, who received RGX-202 at the higher dose level of RGX-202, microdystrophin expression was measured to be 75.7 percent compared to control at three months. A 77 percent reduction from baseline in serum creatinine kinase (CK) levels, a measure of muscle injury that is common in people with DMD, was observed at ten weeks.

All four patients, across both dose levels, who completed three-month trial assessments indicate encouraging increases in expression of RGX-202 microdystrophin and reduction from baseline in serum CK levels, supporting evidence of clinical improvement.

Photo: Kenneth Mills, president and CEO of RegenexBio