REGENXBIO Presents Interim Clinical Data from Phase I/II AFFINITY DUCHENNE™ Trial of RGX-202 at 28th Annual International Congress of the World Muscle Society
- RGX-202, a potential one-time AAV Therapeutic for the treatment of Duchenne that includes an optimized transgene for a novel microdystrophin, continues to be well-tolerated in three patients from dose level 1 (1x1014 GC/kg)
- Initial biomarker data in two patients who completed three-month assessment demonstrate robust microdystrophin expression with localization to the muscle cell membrane
- Patient aged 4.4 years old had expression level at 38.8% of control
- Trial dose escalation expected by end of 2023
- Pivotal dose determination and initiation of pivotal program anticipated in 2024
- Plan to use RGX-202 microdystrophin as a surrogate endpoint to support a Biologics License Application filing using the accelerated approval pathway
- RGX-202 development program uses commercial-ready cGMP material from the REGENXBIO Manufacturing Innovation Center
- Conference call today,
Tuesday, October 3, 2023, at 4:30 p.m. ET
"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," said
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 (1x1014 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.
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," said Aravindhan Veerapandiyan, M.D., Pediatric Neuromuscular Neurologist,
Clinical Program Updates
The Company expects to share initial strength and functional assessment data for both dose levels in 2024. Additionally,
"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," said
Conference Call Details
Listeners can register for the webcast via this link. Analysts wishing to participate in the question and answer session should use this link. A copy of the slides being presented will be available via the Company's investor website. Those who plan on participating are advised to join 15 minutes prior to the start time. A replay of the webcast will also be available via the Company's investor website approximately two hours after the call's conclusion.
AFFINITY DUCHENNE Trial Design
The Phase I/II 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 (IV) dose of RGX-202 in patients with Duchenne. 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 doses of 1x1014 genome copies (GC)/kg body weight (n=2) and 2x1014 GC/kg body weight (n=2). 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 trial design consists of thorough safety measures 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 (NSAA) and timed function tests. Initial trial sites are located in the
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 (Spc5-12).
About 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.
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