REGENXBIO Inc. (Nasdaq: RGNX) today reported new, positive interim data from two additional patients in the Phase I/II portion of the AFFINITY DUCHENNE® trial of RGX-202, a differentiated investigational gene therapy for Duchenne muscular dystrophy (Duchenne). Results were presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference.
“RGX-202 is the only next generation gene therapy for Duchenne in a pivotal phase trial. The new data from the age 1-3 cohort builds on the favorable safety and efficacy profile seen in ages 4 and older and reinforces the potential of RGX-202 to serve a wide age range of patients,” said Steve Pakola, M.D., Chief Medical Officer of REGENXBIO. “The consistent, robust microdystrophin levels seen across the age range as well as the functional improvements previously reported support RGX-202’s potential to alter the course of this devastating disease. We look forward to sharing additional Phase I/II functional data in the first half of 2025. We also continue to rapidly advance the pivotal trial towards completing enrollment this year and BLA submission mid-2026.”
“Patients with Duchenne continue to be in need of treatment options that could meaningfully impact the course of disease,” said Carolina Tesi-Rocha, M.D., Stanford Children’s Hospital. “The microdystrophin expression and biomarker data presented represent key indicators of potential therapeutic effect. Combined with the safety and functional data to date, I am highly encouraged by the profile of RGX-202.”
AFFINITY DUCHENNE Phase I/II Interim Data Updates
Biomarker Data
New biomarker data from two patients who received the pivotal dose of RGX-202 were presented at MDA and continue to support consistent, robust expression and transduction of RGX-202 microdystrophin across all ages.
In a patient aged 3 at dosing, microdystrophin expression was measured to be 122.3% compared to control. Patients under 4 years old have no access to gene therapy, and REGENXBIO is the only gene therapy sponsor recruiting patients in this age group in the U.S.
In a patient aged 7 years old, RGX-202 microdystrophin expression was measured to be 31.5% compared to control.
In all patients, RGX-202 was appropriately localized to the sarcolemma, demonstrating the differentiated construct with the CT-Domain is appropriately targeting the muscle. RGX-202 microdystrophin expression results in ambulatory patients aged 8+ are the highest reported microdystrophin levels across approved or investigational gene therapies. To support a Biologics License Application (BLA) using the accelerated approval pathway, the primary endpoint in the pivotal phase of AFFINITY DUCHENNE is the proportion of participants whose RGX-202 microdystrophin expression is ≥10% at Week 12.
RGX-202 also continues to demonstrate the highest reported vector genome copies (4.9-55.4) measured by qPCR across approved or investigational gene therapies.
Safety and Tolerability Data
As of February 21, 2025, RGX-202 was well tolerated with no serious adverse events (SAEs) and no AEs of special interest (AESIs). Common drug-related AEs included nausea, vomiting and fatigue. All resolved and are typically anticipated with gene therapy administration. A thorough, proactive, short-course immune modulation regimen in combination with industry-leading product purity levels of more than 80% full capsids may contribute to the favorable safety profile seen in patients receiving RGX-202 to date.
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RGX-202 Treatment |
Dose Level 1 Dose Evaluation (1×1014 GC/kg) |
Dose Level 2 Younger Boys (2×1014 GC/kg)
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Dose Level 2 Dose Evaluation / (2×1014 GC/kg) |
Total n=11 |
|
|
Age Range (number dosed) |
4-11 (n=3) |
1-3 (n=1) |
4-11 (n=7) |
All Ages
|
|
|
SAE |
0 |
0 |
0 |
0 |
|
|
AESI |
Central or peripheral neurotoxicity |
0 |
0 |
0 |
0 |
|
Drug-induced liver injury |
0 |
0 |
0 |
0 |
|
|
Thrombocytopenia |
0 |
0 |
0 |
0 |
|
|
Myocarditis |
0 |
0 |
0 |
0 |
|
|
Myositis |
0 |
0 |
0 |
0 |
|
As reported in November 2024, the first five participants in the Phase I/II portion of the AFFINITY DUCHENNE trial all showed functional improvements that exceeded external natural history controls, demonstrating evidence of RGX-202 positively impacting disease trajectory. Patients demonstrated stable or improved function on the North Star Ambulatory Assessment (NSAA) and timed function tests. REGENXBIO plans to share additional interim functional data in the first half of 2025.
About RGX-202
RGX-202 is a potential best-in-class investigational gene therapy designed for improved function and outcomes in Duchenne. RGX-202 is the only gene therapy approved or in late-stage development for Duchenne with a differentiated microdystrophin construct that encodes key regions of naturally occurring dystrophin, including the C-Terminal (CT) domain. In preclinical studies, the CT domain has been shown to protect the muscle from contraction-induced stress and improve its ability to repair itself.
Additional design features may potentially improve gene expression, increase protein translation efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of microdystrophin throughout skeletal and heart muscle using the NAV® AAV8 vector and a well-characterized muscle-specific promoter (Spc5-12). RGX-202 is manufactured using REGENXBIO’s proprietary, high-yielding NAVXpress™ suspension-based platform process.