BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale.

Abstract

Dual inhibition of angiopoietin-2 and VEGF-A with faricimab (Vabysmo) offers excellent visual acuity gains with strong durability in patients with diabetic macular edema (ME) and neovascular age-related macular degeneration. The phase III BALATON/COMINO (NCT04740905/NCT04740931) trials will investigate the efficacy, safety, and durability of faricimab in patients with ME due to retinal vein occlusion (RVO). Two identically designed global, randomized, double-masked, active comparator-controlled studies. Anti-VEGF treatment-naive patients with branch, central, or hemiretinal RVO. Patients were randomized to 6 monthly injections of faricimab 6.0 mg or aflibercept 2.0 mg. From weeks 24 to 72, all patients received faricimab 6.0 mg administered in up to 16-week intervals using an automated treatment algorithm to generate a treat-and-extend-based personalized treatment interval dosing regimen. Personalized treatment interval adjustments were based on changes in central subfield thickness (CST) and best-corrected visual acuity (BCVA). Primary end point was noninferiority of faricimab versus aflibercept in mean change from baseline in BCVA (week 24; noninferiority margin: 4 letters). Secondary end points (weeks 0-24) were mean change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire 25 composite score; proportion of patients gaining or avoiding loss of ≥ 15/≥ 10/≥ 5/> 0 letters. Secondary end points (weeks 24-72) were treatment durability (week 68); continuation of weeks 0 to 24 end points. Ocular/nonocular adverse events will be assessed. In total, 1282 patients across 22 countries were enrolled (BALATON, 553 patients, 149 centers; COMINO, 729 patients, 193 centers). Using a novel automated interval algorithm, BALATON/COMINO will evaluate the efficacy and safety of faricimab for ME secondary to RVO and provide key insights into how to personalize treatment. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.