NEW YORK – Regenxbio on Monday said it has dosed the first patient in the pivotal stage of its ongoing AFFINITY Duchenne clinical trial evaluating its gene therapy RGX-202 for Duchenne muscular dystrophy.
The multicenter, open-label Phase I/II/III trial will evaluate the efficacy of RGX-202 at the second dose level examined in the Phase I/II portion of the study. RGX-202 uses an adeno-associated virus serotype 8 vector to deliver a gene encoding a novel microdystrophin that includes key components of naturally occurring dystrophin, such as the C-terminal domain. Duchenne, a severe, progressive and degenerative muscle disease, is caused by mutations in the gene encoding dystrophin, which is involved in muscle cell structure and signaling pathways.
The pivotal trial is enrolling 30 ambulatory patients ages 1 and older. Investigators will evaluate as the primary endpoint the portion of patients with RGX-202 microdystrophin levels at or above 10 percent at week 12. Secondary endpoints will include changes from baseline on timed function tests for participants 4 years of age and older, and for younger children on measures of gross and fine motor skills and stride velocity.
The first five participants treated at both dose levels in the Phase I/II portion of the study experienced functional improvements on ambulatory tests and had improved performance as compared to natural history controls, the company reported. It additionally said that biomarker data indicated consistent, high expression, and transduction of the RGX-202 microdystrophin and that it was localized to the muscle tissue targeted. Common drug-related adverse events included nausea, vomiting, and fatigue, which all resolved. No serious adverse events were reported in this cohort.
Rockville, Maryland-based Regenxbio expects the pivotal trial to support the submission of a biologics license application with the US Food and Drug Administration under the accelerated approval pathway in 2026.
"The initiation of our pivotal trial and newly released positive functional data are exciting milestones on our path to rapidly deliver RGX-202, the only next generation gene therapy in pivotal phase, to the Duchenne community," Regenxbio President and CEO of Curran Simpson said in a statement. "The totality of our data demonstrates that RGX-202 provides evidence of improving outcomes for boys with Duchenne."
In June, the FDA converted the accelerated approval previously awarded to Sarepta Therapeutics' Elevidys (delandistrogene moxeparvovec) for Duchenne muscular dystrophy to a traditional approval and expanded its indication to patients 4 years of age and older.