Gene Therapy RGX-202 Demonstrates Favorable Safety Profile in AFFINITY DUCHENNE Trial

An investigational adeno-associated virus (AAV) gene therapy, RGX-202, demonstrated favorable tolerability and robust microdystrophin expression in boys with Duchenne muscular dystrophy (DMD) in interim findings from the ongoing phase 1/2 AFFINITY DUCHENNE trial (NCT05693142). The therapy, designed to deliver an optimized microdystrophin gene using a NAV AAV8 vector, is being evaluated as a one-time treatment intended to address the underlying genetic cause of the disease.¹

DMD is a rare, X-linked neuromuscular disorder caused by mutations in the DMD gene that disrupt production of dystrophin, a structural protein essential for maintaining muscle integrity. The disease is characterized by progressive muscle degeneration leading to loss of ambulation, respiratory compromise, cardiomyopathy, and premature mortality.²

AFFINITY DUCHENNE Study Design

Led by Carolina Tesi Rocha, MD, director of the Pediatric EMG Laboratory at Lucile Packard Children’s Hospital Stanford in California, AFFINITY DUCHENNE is a multicenter, open-label clinical trial assessing the safety, tolerability, and efficacy of RGX-202 in ambulatory boys with DMD.¹ The phase 1/2/3 portion of the study enrolled boys aged 1 to 11 years at screening who received a single intravenous infusion of RGX-202 at 1 of 2 dose levels: 1 × 10¹⁴ genome copies/kg (dose level 1) or 2 × 10¹⁴ genome copies/kg (pivotal dose).¹

The broader phase 3 portion of the study is evaluating the therapy in boys older than 1 year of age, with an additional confirmatory cohort currently enrolling. Investigators incorporated a short-course immune modulation regimen into the protocol to address potential safety risks associated with high-dose AAV gene therapy.¹

Functional and Safety Outcomes

Preliminary functional findings also suggested potential clinical benefit. Among participants treated at the pivotal dose, motor function outcomes at 12 months exceeded expected trajectories based on matched external natural history comparisons and predictive modeling using the Clinical Trial Analysis Platform (cTAP).¹

In addition, the observed improvements surpassed the minimal clinically important difference threshold in the small group of evaluated participants (n = 4), suggesting early signals of functional benefit following treatment with RGX-202.¹

As of the May 7, 2025 data cutoff, interim data from 13 treated participants indicated that RGX-202 was generally well tolerated, with no serious adverse events (AEs) or AEs of special interest reported.¹ Notably, investigators observed no evidence of liver injury, a potential concern associated with high-dose AAV gene therapy.¹

All told, biomarker analyses demonstrated consistent transduction and microdystrophin protein expression in muscle tissue.¹ Expression levels exceeded 10% relative to normal control samples, with values ranging from 10.4% to 83.4% in the lower-dose cohort (n = 3) and from 20.8% to 122.3% in participants treated at the pivotal dose (n = 9).¹

Clinical Context and Conclusion

Gene replacement strategies have emerged as a promising therapeutic approach for DMD, aiming to deliver shortened versions of the dystrophin gene capable of restoring partial protein function in skeletal muscle.² RGX-202 specifically encodes a microdystrophin construct containing a C-terminal domain designed to support improved muscle function and preservation of muscle health.¹

Read more: Patients Treated With Regenxbio’s DMD Gene Therapy RGX-202 Exceed Expected Disease Trajectory on NSAA

Investigators concluded that RGX-202 demonstrated favorable tolerability alongside robust microdystrophin expression and early signals of functional improvement up to 12 months following treatment in boys with DMD. Ongoing portions of the AFFINITY DUCHENNE trial are expected to further evaluate the therapy’s long-term safety and clinical efficacy.¹

REFERENCES
1. Tesi Rocha C, Veerapandiyan A, Iannaccone S, et al. RGX-202, An investigational gene therapy for the treatment of Duchenne muscular dystrophy: Interim Phase I/II clinical data. Presented at: Muscular Dystrophy Association (MDA) Clinical and Scientific Conference; March 8-11, 2026; Orlando, Florida
2. National Institute of Neurological Disorders and Stroke. Muscular dystrophy. March 25, 2025. Accessed March 10, 2026. https://www.ninds.nih.gov/health-information/disorders/muscular-dystrophy