REGENXBIO Inc. announced additional interim safety data and initial efficacy data from the Phase I/II AFFINITY DUCHENNE trial of RGX-202 for the treatment of Duchenne Muscular Dystrophy (Duchenne). Results were shared at the 28th Annual International Congress of the World Muscle Society.

“Duchenne is a rare degenerative disease, and without a functional dystrophin protein, muscles progressively weaken, leading to loss of mobility and declining respiratory and cardiac function,” says Olivier Danos, PhD, chief scientific officer of REGENXBIO. “The unique construct of RGX-202, inclusive of the C-Terminal domain, has the potential to make a meaningful impact for patients and we are encouraged by these interim safety and efficacy results.”

RGX-202 is an investigational one-time AAV therapeutic for Duchenne, using the NAV® AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain as well as a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne.

Data were presented from dose level 1 (1×1014 genome copies (GC)/kg body weight) of the ongoing Phase I/II AFFINITY DUCHENNE trial, which continues to recruit ambulatory patients (aged 4 to 11 years) and is using commercial-ready cGMP material from the REGENXBIO Manufacturing Innovation Center.

Safety Update

As of September 28, 2023, RGX-202 was reported to be well tolerated with no drug-related serious adverse events in three patients, aged 4.4, 10.6 and 6.3 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.

Biomarker Data

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 patient aged 4.4 years old, RGX-202 microdystrophin expression was measured to be 38.8% compared to control. A reduction from baseline in serum creatinine kinase (CK) levels of 43% was observed at ten weeks, supporting evidence of clinical improvement. Elevated CK levels are associated with muscle injury and are uniformly elevated in patients with Duchenne.

In the patient aged 10.6 years old, RGX-202 microdystrophin expression was measured to be 11.1% compared to control and a reduction from baseline in serum CK levels of 44% was observed at ten weeks.

“I am encouraged by these initial results demonstrating that RGX-202 appears to be well tolerated and leads to robust microdystrophin expression in muscle tissue, which are important early findings,” says Aravindhan Veerapandiyan, MD, pediatric neuromuscular neurologist, Arkansas Children’s Hospital, and primary investigator in the trial. “I know that there is still unmet need for these boys for new treatment options that have the potential to impact the trajectory of the disease.”

Clinical Program Updates

REGENXBIO expects to dose patients at dose level 2 (2×1014 genome copies (GC)/kg body weight) in the Phase I/II AFFINITY DUCHENNE trial by the end of 2023. In addition, the trial protocol has been amended to accelerate the development of RGX-202, updating the dose expansion phase of the trial to begin after two patients, from the previous three patients.

Today, REGENXBIO also provided an update on a newly completed preclinical efficacy study evaluating RGX-202 manufactured using REGENXBIO’s NAVXpress™ commercial-ready process at both dose levels. RGX-202 at dose level 2 showed improvement in functional performance, compared to dose level 1, as determined by forelimb muscle strength and treadmill exhaustion in mdx mice. This data further supports plans to immediately initiate dose escalation to dose level 2.

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 are pleased to share these encouraging results and updates, enabling us to accelerate our development of RGX-202 with the goal of reaching pivotal phase faster,” says Kenneth T. Mills, president and chief executive officer of REGENXBIO. “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. 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.”