RGX-202 demonstrates positive phase 3 results for Duchenne muscular dystrophy

RegenxBio reported positive topline results from the pivotal phase 3 portion of the AFFINITY DUCHENNE study, with the investigational gene therapy RGX-202 meeting its primary biomarker end point in ambulatory boys with Duchenne muscular dystrophy (DMD). According to the company, 93% of treated participants achieved more than 10% microdystrophin expression at week 12 (n=30; P<.0001), and interim data suggested an association between microdystrophin expression and functional change at 1 year.¹

“These topline results are exciting for the Duchenne community,” Pat Furlong, founding president of Parent Project Muscular Dystrophy, said in the company’s release.¹ Clinically, the update is notable because it adds to the still-evolving evidence base around microdystrophin as a surrogate end point in DMD, an issue central to current regulatory decisions for adeno-associated virus (AAV) gene therapies in this disease.^2,3

DMD is an X-linked progressive neuromuscular disorder caused by pathogenic variants in the dystrophin gene, leading to absent or severely reduced dystrophin, progressive weakness, loss of ambulation, cardiomyopathy, respiratory failure, and shortened survival.⁴ Corticosteroids remain a mainstay of care, while exon-skipping therapies benefit only molecularly eligible subgroups.⁴ Delandistrogene moxeparvovec became the first gene therapy cleared in the US for DMD, initially through accelerated approval and later with broader labeling, but questions have persisted regarding the relationship between microdystrophin expression and functional benefit across programs.^2,3

AFFINITY DUCHENNE is described by the sponsor as a phase 1/2/3 trial. In the pivotal portion, RGX-202 was administered at 2×10^14 genome copies/kg to 31 ambulatory boys 1 year and older.¹ The interim analysis included safety data for 31 participants, biomarker data for 30 participants with week 12 biopsy samples, and 12-month functional data for 9 participants older than 4 years at dosing.¹ The company also said more than 20 additional participants had enrolled in a confirmatory cohort, with dosing across 60 patients expected to be completed by midyear.¹

The primary end point was microdystrophin expression at week 12. RegenxBio reported a mean microdystrophin expression of 71.1% across all evaluated participants and 41.6% in boys older than 8 years; 80% of participants reportedly achieved more than 40% expression.¹ The company further stated that the transgene product localized to the sarcolemma, consistent with intended protein targeting.¹

Functional findings remain preliminary. In 9 participants aged about 5 to 12 years, the company said RGX-202-treated patients showed statistically significant improvement at 1 year on the North Star Ambulatory Assessment and timed tests compared with external controls using propensity score weighting.¹ RegenxBio also reported a statistically significant correlation between week 12 microdystrophin expression and 1-year change in North Star Ambulatory Assessment scores.¹ However, these data have not yet been peer reviewed, and the use of external controls rather than a randomized concurrent comparator remains an important interpretive limitation.

The company characterized RGX-202 as well tolerated overall, with 2 serious adverse events: subacute myocarditis in an 8-year-old participant and asymptomatic liver injury in a 10-year-old participant; both reportedly resolved without sequelae.¹ Common treatment-related adverse events were vomiting, fatigue, and nausea, described as mild to moderate.¹ Hepatic and cardiac toxicities are already established concerns with systemic AAV-mediated gene transfer, and longer follow-up will be important.^2,3

RGX-202 is an investigational AAV gene therapy designed to deliver a microdystrophin construct that, according to the company, includes a C-terminal domain intended to support muscle function.¹ RegenxBio said recent discussions with the FDA indicated that correlation between microdystrophin expression and clinical outcomes would be relevant to evaluating the surrogate end point, and that externally controlled trials may be considered in some circumstances.¹ The company plans to pursue accelerated approval in 2027.¹

For clinicians, the readout is best viewed as an encouraging but still interim signal. The biomarker result appears robust, but the functional data set is small, nonrandomized, and based on external comparisons. Whether those findings will satisfy regulators—and, more importantly, translate into durable clinical benefit across the broad DMD population—will depend on complete confirmatory data and longer-term safety follow-up.

References

1. RegenxBio announces positive topline results from pivotal phase III AFFINITY DUCHENNE study of RGX-202. News release. RegenxBio. May 14, 2026. Accessed May 14, 2026. https://www.prnewswire.com/news-releases/regenxbio-announces-positive-topline-results-from-pivotal-phase-iii-affinity-duchenne-study-of-rgx-202-302771834.html
2. Elevidys. Prescribing information. Sarepta Therapeutics; 2023. Accessed May 14, 2026. https://www.fda.gov/files/vaccines,%20blood%20&%20biologics/published/Package-Insert-ELEVIDYS_1.pdf
3. US Food and Drug Administration. Center for Biologics Evaluation and Research review documents for delandistrogene moxeparvovec. Accessed May 14, 2026.
4. Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018;17(3):251-267. doi:10.1016/S1474-4422(18)30024-3