REGENXBIO reports positive Phase I/II AFFINITY DUCHENNE results showing improved function, strong microdystrophin expression, and favorable safety for RGX-202 gene therapy in Duchenne muscular dystrophy.
Written By: Chikkula Pavan Kumar PharmD and Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
REGENXBIO Inc. reported positive interim results from the Phase I/II AFFINITY DUCHENNE trial (NCT05693142) evaluating RGX-202, an investigational gene therapy designed to deliver a functional microdystrophin protein for the treatment of Duchenne muscular dystrophy (DMD). The updated dataset, presented at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, includes functional outcomes, biomarker data, cardiac MRI results, and safety findings.
Duchenne muscular dystrophy is a rare genetic disorder caused by mutations in the dystrophin gene, which normally helps maintain muscle structure. Without dystrophin, muscles progressively weaken and degenerate, eventually leading to loss of mobility, heart complications, and premature death. The disease primarily affects boys and occurs in roughly 1 in 3,500 to 5,000 male births worldwide.
Steve Pakola, M.D., Chief Medical Officer of REGENXBIO, said the interim results show sustained functional benefit, stable cardiac health, and a favorable safety profile through up to two years after treatment, supporting the potential of RGX-202 as a differentiated gene therapy for Duchenne.
Functional Improvements Observed
Functional outcomes were assessed in seven participants aged approximately 6–12 years who received the pivotal dose of 2×10¹⁴ genome copies per kilogram. At one year, patients showed improvements on the North Star Ambulatory Assessment (NSAA) and across timed functional tests including Time to Stand, the 10-meter walk-run test, and Time to Climb.
Investigators compared patient outcomes with expected disease progression using the cTAP disease progression model and external control analyses. Participants treated with RGX-202 exceeded predicted disease trajectories, improving an average of +4.9 NSAA points compared with expected decline. Among older participants aged eight years and above (n=5), improvement averaged +5.2 points, despite this age group typically showing functional deterioration.
Participants treated at the lower 1×10¹⁴ GC/kg dose also showed durable benefit, demonstrating an average +5.6-point NSAA improvement at two years compared with predicted progression.
Cardiac MRI assessments indicated stable heart function at one-year post-treatment, including preserved left ventricular ejection fraction, global circumferential strain, and no evidence of worsening fibrosis.
Biomarker Data Support Microdystrophin Expression
Biomarker data from 13 treated participants showed consistent expression of RGX-202 microdystrophin, a shortened version of the dystrophin protein designed to restore key muscle-stabilizing functions.
A newly evaluated patient aged 3.6 years demonstrated 51.2% microdystrophin expression at Week 12. The pivotal phase of the AFFINITY DUCHENNE study uses the proportion of patients achieving greater than 10% microdystrophin expression at Week 12 as its primary endpoint.
Investigators also confirmed that the protein localized to the sarcolemma, the membrane surrounding muscle cells. This localization is supported by the therapy’s construct, which includes the C-terminal domain of dystrophin, a structural region believed to help stabilize muscle fibers.
RGX-202 uses an AAV8 viral vector to deliver the gene therapy to skeletal and cardiac muscle, combined with a muscle-specific promoter designed to drive targeted microdystrophin expression.
Safety Findings
Across 13 treated participants, investigators reported no serious adverse events or adverse events of special interest as of the January 5, 2026 data cutoff.
Laboratory monitoring showed no evidence of liver injury, with gamma-glutamyl transferase (GGT) and bilirubin remaining within normal ranges for up to two years. Reductions were also observed in muscle damage biomarkers including creatine kinase, ALT, AST, and LDH.
The most common treatment-related adverse events were vomiting, fatigue, and nausea, which are commonly associated with gene therapy administration.
Next Steps
The AFFINITY DUCHENNE study is ongoing, and REGENXBIO expects to report topline pivotal data in early Q2 2026. The company plans to request a pre-Biologics License Application meeting with the U.S. FDA in mid-2026.
In parallel, the company is enrolling approximately 30 participants aged one year and older in a confirmatory trial and expects most participants to be enrolled before submitting a potential BLA.
Reference
Regenxbio reports new positive interim data from Phase I/II affinity Duchenne® trial of RGX-202, 11 March 2026, REGENXBIO REPORTS NEW POSITIVE INTERIM DATA FROM PHASE I/II AFFINITY DUCHENNE® TRIAL OF RGX-202 | Regenxbio Inc
AFFINITY DUCHENNE: RGX-202 Gene Therapy in Participants with Duchenne Muscular Dystrophy (DMD), ClinicalTrials.gov ID NCT05693142, https://clinicaltrials.gov/study/NCT05693142
About the Writer
Chikkula Pavan Kumar, PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.
About the Writer
Nikita Jha BPharm is a pharmacy graduate with expertise in clinical research, pharmacovigilance, and medical writing. In her words, she is passionate about translating complex scientific data into clear, accurate healthcare communications that advance drug safety and patient care.