Sozinibercept Combination Therapy for Neovascular Age-related Macular Degeneration: Phase 2b Study Subgroup Analysis by Lesion Type

Background and Objective The purpose of this study was to evaluate the angiographic predictors of response to the anti-vascular endothelial growth factor-C/-D agent, sozinibercept. Patients and Methods Prespecified and post hoc subgroup analyses of a phase 2b, randomized, double-masked, sham-controlled trial of 240 participants with treatment-naïve neovascular age-related macular degeneration, comparing monthly intravitreal sozinibercept 0.5 mg or 2 mg, plus ranibizumab 0.5 mg, versus monthly ranibizumab monotherapy. Results Visual acuity benefits at week 24 were greatest in participants with occult lesions receiving 2 mg sozinibercept combination therapy (+15.65 [ n = 53] letters versus +9.62 [ n = 51] with ranibizumab monotherapy; least squares mean difference +6.03; P = 0.0009). A composite analysis of occult and minimally classic lesions excluding retinal angiomatous proliferation ( n = 175/240) also favored sozinibercept over control (+16.08 versus +10.34 letters; +5.74; P = 0.0002). Structural outcomes mirrored sozinibercept visual acuity benefits, with less leakage and smaller lesions on multimodal imaging. Conclusion Angiographic lesion characteristics were found to predict the response to sozinibercept combination therapy. [ Ophthalmic Surg Lasers Imaging Retina 2025;56:XX–XX.]