Diabetic retinopathy remains the leading cause of blindness in working-age adults globally, and proliferative diabetic retinopathy—the advanced neovascular stage—requires repeated intravitreal injections of anti-VEGF agents to suppress disease. That treatment burden, six to twelve injections per year indefinitely, is what AbbVie’s gene therapy program is designed to eliminate.
NAAVIGATE (NCT07592273) is a phase 2b/3 randomized, sham-controlled trial enrolling 576 patients with proliferative diabetic retinopathy across sites in the United States, Europe, and Asia-Pacific. Participants receive either a single suprachoroidal injection of surabgene lomparvovec (ABBV-RGX-314) or a sham procedure. The gene therapy delivers an AAV8 vector encoding a soluble anti-VEGF protein designed to provide sustained expression in the retinal pigment epithelium, with the goal of converting an injection-dependent treatment to a one-time intervention.
Surabgene lomparvovec emerged from AbbVie’s collaboration with RegenxBio, which developed the proprietary AAV8 vector and suprachoroidal delivery system. Earlier phase 2 data in wet age-related macular degeneration, a related anti-VEGF indication, showed sustained biologic expression at 36 months following suprachoroidal delivery.
NAAVIGATE is the pivotal read that will determine whether the gene therapy platform can deliver on that promise in diabetic retinopathy—a larger, younger, and more heterogeneous patient population than AMD. The trial’s 576-patient size reflects the statistical power needed to detect a durable visual acuity benefit against a background of standard-of-care intravitreal injection eligibility for patients who progress.
Enrollment has opened at investigational sites with anticipated completion in 2028. The primary endpoint is best-corrected visual acuity change from baseline at 24 months. Secondary endpoints include the proportion of patients who remain injection-free through the primary analysis period.