47-OR: Efficacy, Durability, and Safety of Faricimab in Diabetic Macular Edema: Two-Year Results from the Phase 3 YOSEMITE and RHINE Trials

Diabetic macular edema (DME) is a major cause of vision loss for people with diabetes. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for DME; however, there is an unmet need for new strategies that address the multifactorial nature of DME, reduce treatment burden, and optimize patient outcomes. Angiopoietin-2 and VEGF-A synergistically drive vascular instability in DME; therefore, dual pathway inhibition with faricimab, the first bispecific antibody designed for intraocular use, may promote vascular stability and durable efficacy beyond current anti-VEGF therapies. YOSEMITE (NCT03622580) and RHINE (NCT03622593) were randomized, double-masked, active comparator-controlled, phase 3 trials designed to assess the efficacy, durability, and safety of faricimab in patients with DME (YOSEMITE, N = 940; RHINE, N = 951) . Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks (Q8W) after 6 initial every-4-week (Q4W) doses, faricimab 6.0 mg per personalized treatment interval (PTI) after 4 initial Q4W doses, or aflibercept 2.0 mg Q8W after 5 initial Q4W doses. The PTI algorithm was a protocol-driven treat-and-extend regimen, with dosing intervals extended, maintained, or reduced (from Q4W up to every 16 weeks [Q16W]) based on prespecified vision and anatomic criteria. Efficacy and safety endpoints were assessed at Q4W study visits through week 100. At 1 year, faricimab Q8W or per PTI offered durable vision gains that were noninferior to aflibercept Q8W and were achieved with Q16W dosing in > 50% of patients in the PTI arms. Faricimab Q8W or per PTI demonstrated anatomic improvements versus aflibercept Q8W and was well tolerated, with low rates of intraocular inflammation. Year 2 results from YOSEMITE/RHINE will be presented at the meeting, and will examine whether early vision gains, anatomic improvements, and extended (up to Q16W) dosing with faricimab are maintained over 2 years. Disclosure C.J. Danzig: Advisory Panel; Genentech, Inc. Consultant; Adverum Biotechnologies, Genentech, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals Inc. Research Support; Adverum Biotechnologies, Genentech, Inc., Kodiak Pharmaceuticals, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals Inc., Roche Pharmaceuticals. Speaker's Bureau; Novartis Pharmaceuticals Corporation. J.A. Wells: Advisory Panel; Genentech, Inc. Research Support; Adverum, Alimera, Bayer AG, DRCR Retina Network, Genentech, Inc., Gyroscope, Iveric, Kodiak, Lowy Medical institute, Regeneron Pharmaceuticals Inc. D. Eichenbaum: Consultant; Genentech, Inc., Regeneron Pharmaceuticals Inc. Research Support; Bayer AG, Genentech, Inc., Regeneron Pharmaceuticals Inc. Speaker's Bureau; Bayer AG, Genentech, Inc. J.I. Lim: Consultant; Cognition, Eyenuk, Genentech, Inc., Iveric Bio, Novartis AG, Quark, Santen, Luxa, Veridian, Aura, Unity. Research Support; Aldeyra, Chengdu Pharmaceuticals, Regeneron Pharmaceuticals Inc., Stealth, NGM. K. Asik: None. Z. Haskova: Employee; Genentech, Inc. S. Mohan: None. D. Silverman: Employee; Roche Pharmaceuticals. Y. Tang: Employee; Genentech, Inc. H. Lin: Employee; Genentech, Inc. Funding F. Hoffmann-La Roche Ltd. (Basel, Switzerland)