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

Lars-Olof Hattenbach; Francis Abreu; Pablo Arrisi; Karen Basu; Carl J Danzig; Robyn Guymer; Zdenka Haskova; Jeffrey S Heier; Aachal Kotecha; Ying Liu; Anat Loewenstein; András Seres; Jeffrey R Willis; Charles C Wykoff; Liliana P Paris

doi:10.1016/j.xops.2023.100302

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

Ophthalmol Sci. 2023 Mar 27;3(3):100302. doi: 10.1016/j.xops.2023.100302. eCollection 2023 Sep.

Authors

Affiliations

¹ Augenklinik des Klinikums Ludwigshafen, Ludwigshafen, Germany.
² Genentech, Inc., South San Francisco, California.
³ Roche Products Ltd., Welwyn Garden City, UK.
⁴ Roche Products (Ireland), Dublin, Ireland.
⁵ Rand Eye Institute, Deerfield Beach, Florida.
⁶ Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
⁷ The Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, East Melbourne, Australia.
⁸ Ophthalmic Consultants of Boston, Boston, Massachusetts.
⁹ Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel.
¹⁰ Budapest Retina Associates, Budapest, Hungary.
¹¹ Retinal Consultants of Texas, Houston, Texas.

Abstract

Purpose: 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).

Design: Two identically designed global, randomized, double-masked, active comparator-controlled studies.

Participants: Anti-VEGF treatment-naive patients with branch, central, or hemiretinal RVO.

Methods: 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).

Main outcome measures: 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.

Results: In total, 1282 patients across 22 countries were enrolled (BALATON, 553 patients, 149 centers; COMINO, 729 patients, 193 centers).

Conclusions: 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.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Angiopoietin-2; Faricimab; Macular edema; Retinal vein occlusion; Vascular endothelial growth factor receptor.