First Patient Dosed in Phase 2b/3 NAAVIGATE Trial of Gene Therapy Surabgene Lomparvovec in Diabetic Retinopathy

REGENXBIO Inc. announced the first patient has been dosed in the phase 2b/3 NAAVIGATE clinical trial of investigational surabgene lomparvovec (sura-vec; ABBV-RGX-314), a one-time gene therapy for diabetic retinopathy (DR), triggering a $100 million milestone payment from AbbVie under the companies' existing collaboration.¹ The dosing marks the transition of the sura-vec program into pivotal-stage development for DR following encouraging two-year data from the earlier phase 2 ALTITUDE trial.

Diabetic retinopathy is the leading cause of vision loss in adults between 24 and 75 years of age worldwide and affects nearly 10 million Americans.¹ The current standard of care relies on anti-VEGF intravitreal injections, which must be administered repeatedly, often monthly or bimonthly, to maintain their protective effect. <cite index="19-1">Real-world clinical studies have repeatedly shown that patients are often undertreated compared to standards in clinical trials, with anti-VEGF frequencies in practice ranging from 2.2 to 4.4 injections per year for diabetic macular edema</cite>, well below the dosing intensity that produces optimal outcomes in controlled settings. <cite index="17-1">One-fifth of patients report fear of injections as a major barrier to treatment, contributing to nonadherence and undertreatment.</cite> The result is a treatment landscape in which disease progression continues even in treated patients, with a meaningful proportion eventually developing vision-threatening proliferative disease despite access to therapy.

Sura-vec uses the NAV AAV8 vector to deliver a gene encoding an anti-VEGF antibody fragment directly into the retinal tissue, with the goal of enabling the eye to produce its own sustained VEGF inhibition following a single in-office administration. In NAAVIGATE, the drug is delivered via the suprachoroidal route, a minimally invasive approach that places the vector between the choroid and sclera without entering the vitreous cavity, potentially offering advantages in biodistribution and procedure tolerability relative to intravitreal or subretinal delivery.

NAAVIGATE is a multicenter, randomized, masked, sham-controlled study enrolling patients with nonproliferative DR (NPDR) without center-involved diabetic macular edema. Patients will receive sura-vec at 1.0x10¹² genome copies per eye, the dose level evaluated as dose level 3 in the ALTITUDE trial, along with short-course topical prophylactic steroids. The primary endpoint is a greater than 2-step improvement on the Diabetic Retinopathy Severity Scale (DRSS) at one year. The phase 2b portion, operationalized by REGENXBIO, is expected to enroll approximately 135 participants in the United States.

"Diabetic retinopathy 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," Arshad Khanani, MD, MA, FASRS, Director of Clinical Research at Sierra Eye Associates in Reno, Nevada, and a NAAVIGATE investigator, said in a statement.¹ "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."¹

The NAAVIGATE dosing follows two-year data from the ALTITUDE trial presented earlier in 2026 showing that sura-vec at dose level 3 demonstrated a durable efficacy profile and was well tolerated with no intraocular inflammation observed in 15 patients.¹ <cite index="24-1">Preliminary results from the ALTITUDE study have demonstrated improvement in the diabetic retinopathy severity score and a reduction in treatment burden</cite>, consistent with the therapeutic hypothesis that sustained intraocular VEGF inhibition from a single gene therapy administration could reduce dependence on repeated injections. REGENXBIO plans to present two-and-a-half-year ALTITUDE data at the American Society of Retina Specialists 44th Annual Meeting in July 2026.

Sura-vec is also under investigation for wet age-related macular degeneration via subretinal delivery in the pivotal ATMOSPHERE and ASCENT trials, with topline data expected from both studies in Q4 2026.¹ Five-year long-term follow-up data from the phase 1/2a wet AMD subretinal program will also be presented at ASRS.

REFERENCES
1. REGENXBIO announces first patient dosed in phase IIb/III NAAVIGATE trial of surabgene lomparvovec in diabetic retinopathy; company to receive $100 million milestone. News release. REGENXBIO Inc. June 29, 2026. Accessed June 29, 2026. https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-announces-first-patient-dosed-phase-iibiii-naavigate
2. Virgili G, Parravano M, Evans JR, Gordon I, Lucenteforte E. Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis. Cochrane Database Syst Rev. 2023;(12):CD007419. doi:10.1002/14651858.CD007419.pub7. https://doi.org/10.1002/14651858.CD007419.pub7
3. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119(4):789-801. doi:10.1016/j.ophtha.2011.12.039. https://doi.org/10.1016/j.ophtha.2011.12.039