REGENXBIO and AbbVie Dose First Patient in Phase IIb/III NAAVIGATE Trial of One-Time Gene Therapy Sura-vec for Diabetic Retinopathy
Key Insights
REGENXBIO announced the first patient has been dosed in the Phase IIb/III NAAVIGATE trial evaluating surabgene lomparvovec (search) (sura-vec) for diabetic retinopathy (search) using suprachoroidal delivery, triggering a $100 million milestone payment from AbbVie (search).
The multicenter, randomized, sham-controlled study will assess sura-vec at 1.0×10¹² GC/eye in patients with non-proliferative DR without center-involved diabetic macular edema (search), with a primary endpoint of ≥2-step DRSS improvement at one year.
Two-year data from the Phase II ALTITUDE trial showed durable efficacy with no intraocular inflammation (n=15), and longer-term follow-up data will be presented at the ASRS 2026 annual meeting.
REGENXBIO Inc. announced today that the first patient has been dosed in the Phase IIb/III NAAVIGATE clinical trial of investigational surabgene lomparvovec (search) (sura-vec, ABBV-RGX-314) for diabetic retinopathy (search) (DR) using suprachoroidal delivery. The milestone triggers a $100 million payment from collaboration partner AbbVie (search).
"Dosing the first patient in the Phase IIb/III study is a significant milestone in our commitment with AbbVie (search) to bring a one-time gene therapy to patients who continue to face progressive and vision-threatening complications across multiple chronic retinal diseases," said Steve Pakola, M.D., Chief Medical Officer, REGENXBIO. "We are excited to advance sura-vec for DR, following the two-year data that reinforced the durable and disease-modifying impact that sura-vec has the potential to deliver with a single administration."
Trial Design and Endpoints
NAAVIGATE is an operationally seamless Phase IIb/III multicenter, randomized, masked, sham-controlled study evaluating the safety and efficacy of sura-vec in subjects with non-proliferative diabetic retinopathy (search) (NPDR) without center-involved diabetic macular edema (search) (CI-DME). Participants will receive sura-vec at a dose of 1.0×10¹² genome copies (GC) per eye — designated as dose level 3 in the earlier Phase II ALTITUDE trial — along with a short course of topical prophylactic steroids. The primary endpoint is a two-step or greater improvement on the diabetic retinopathy (search) severity scale (DRSS) at one year.
The Phase IIb portion, operationalized by REGENXBIO, is expected to enroll approximately 135 participants in the United States. The study employs a randomized, parallel-group design with double-masking of both patients and outcome assessors, comparing sura-vec plus steroid eye drops against a sham injection with artificial tears, with some participants later permitted to cross over into the active treatment arm. Long-term follow-up will extend to five years after dosing in each eye.
Clinical Rationale and Unmet Need
Diabetic retinopathy (search) is the leading cause of vision loss in adults between 24 and 75 years of age worldwide and affects nearly 10 million people in the United States alone. The spectrum of DR severity ranges from non-proliferative diabetic retinopathy (search) to proliferative diabetic retinopathy (PDR), with a large proportion of patients developing vision-threatening complications including diabetic macular edema (search) (DME) and neovascularization that can lead to blindness.
"Diabetic retinopathy (search) is a leading cause of vision loss among working adults, and the goal as a physician is always to prevent the disease from progressing and treat patients before they lose their vision," said Arshad Khanani, M.D., M.A., FASRS, Director of Clinical Research at Sierra Eye Associates. "Current treatment options often require ongoing, repeated interventions, which can lead to undertreatment and progressive vision-threatening complications. A one-time, in-office treatment has the potential to transform DR management by improving long-term outcomes while making earlier intervention both practical and scalable for patients worldwide."
Current treatment options for patients with NPDR typically include "watchful waiting" or anti-VEGF (search) treatment. For patients with PDR, options include anti-VEGF treatment or retinal laser, with surgical treatment potentially required for advanced PDR.
Supporting Clinical Data
In two-year dose level 3 data from the ALTITUDE trial, sura-vec demonstrated a durable efficacy profile and was well tolerated with no intraocular inflammation observed (n=15), supporting the potential of an in-office gene therapy approach. REGENXBIO plans to present two-and-a-half-year data from the long-term follow-up study of the ALTITUDE trial at the American Society of Retina Specialists (ASRS) 44th Annual Meeting in July 2026.
Five-year long-term follow-up data from the Phase I/IIa study of subretinal sura-vec for wet AMD will also be presented at ASRS. REGENXBIO expects to announce topline data with AbbVie (search) from the ATMOSPHERE and ASCENT pivotal trials of sura-vec using subretinal delivery in the fourth quarter of 2026.
Mechanism of Action
Sura-vec is a one-time investigational gene therapy that uses the NAV AAV8 vector to encode an antibody fragment designed to inhibit vascular endothelial growth factor (VEGF (search)). By inhibiting the VEGF pathway, sura-vec is believed to prevent the growth of new, leaky blood vessels that contribute to fluid accumulation in the retina. The therapy is being developed for wet AMD, diabetic retinopathy (search), and other chronic retinal conditions.