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Additionally, frequent intravitreal injections can prove a burden for patients and caregivers. Angiopoietin-2 (Ang-2) has been explored as an additional therapeutic target, due to the involvement of Ang-2 in DME and nAMD pathogenesis. Recent evidence supports the hypothesis that targeting both VEGF and Ang-2 may improve clinical outcomes in DME and nAMD compared with targeting VEGF alone by enhancing vascular stability, resulting in reduced macular leakage, prevention of neovascularization, and diminished inflammation.\u00a0Faricimab, a novel bispecific antibody that targets VEGF-A and Ang-2, has been evaluated in clinical trials for DME (YOSEMITE\/RHINE) and nAMD (TENAYA\/LUCERNE). These trials evaluated faricimab against the anti-VEGFA\/B and anti\u2013placental growth factor fusion protein aflibercept, both administered by intravitreal injection. In addition to faricimab efficacy, safety, and pharmacokinetics, durability was evaluated during the trials using a treat-and-extend regimen. At 1\u00a0year, faricimab demonstrated non-inferior vision gains versus aflibercept across YOSEMITE\/RHINE and TENAYA\/LUCERNE. In YOSEMITE\/RHINE, faricimab improved anatomic parameters versus aflibercept. Reduction of central subfield thickness (CST), and absence of both DME and intraretinal fluid were greater in faricimab- versus aflibercept-treated eyes. In TENAYA\/LUCERNE, CST reductions were greater for faricimab than aflibercept at the end of the head-to-head phase (0\u201312\u00a0weeks), and were comparable with aflibercept at year 1, but with less frequent dosing. CST and vision gains were maintained during year 2 of both YOSEMITE\/RHINE and TENAYA\/LUCERNE. These findings suggest that dual Ang-2\/VEGF-A pathway inhibition may result in greater disease control versus anti-VEGF alone, potentially addressing the unmet needs and reducing treatment burden, and improving real-world outcomes and compliance in retinal vascular diseases. Long-term extension studies (RHONE-X, AVONELLE-X) are ongoing. Current evidence suggests that dual inhibition with faricimab heralds the beginning of multitargeted treatment strategies inhibiting multiple, independent components of retinal pathology, with faricimab providing opportunities to reduce treatment burden and improve outcomes compared with anti-VEGF monotherapy.<\/jats:p>","DOI":"10.1007\/s00417-024-06531-9","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T06:01:50Z","timestamp":1717740110000},"page":"3437-3451","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Faricimab for neovascular age-related macular degeneration and diabetic macular edema: from preclinical studies to phase 3 outcomes"],"prefix":"10.1007","volume":"262","author":[{"given":"Hansj\u00fcrgen","family":"Agostini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Abreu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline R.","family":"Baumal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolly S.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"G.\u00a0Csaky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Demetriades","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Kodjikian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer I.","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Margaron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi M.","family":"Mon\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tunde","family":"Peto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Ricci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"R\u00fcth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishi P.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivaylo","family":"Stoilov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balakumar","family":"Swaminathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Willis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9841-6220","authenticated-orcid":false,"given":"Peter D.","family":"Westenskow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"6531_CR1","doi-asserted-by":"publisher","unstructured":"Flaxel CJ, Adelman RA, Bailey ST, Fawzi A, Lim JI, Vemulakonda GA, Ying GS (2020a) Age-related macular degeneration Preferred Practice Pattern. 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Francis Abreu is an employee of Genentech, Inc. Caroline R<b>.<\/b> Baumal is a consultant for Alcon and employee of Apellis. Dolly S. Chang is an employee of Genentech, Inc. Karl G. Csaky is a consultant for AbbVie, Adverum, Annexon, Cognition Therapeutics, Endogena, EyeBio, Genentech, Inc., Gyroscope, Heidelberg Engineering, Johnson & Johnson, Merck, NGM Bio, Novartis Pharma AG, Ocular Therapeutix, ReNeuron, Retrotope, and Ribomic; provides contracted research for Alexion, Annexon, Boehringer Ingelheim, Genentech, Inc., Gyroscope, Iveric Bio, and NGM Bio; and is a speaker for Genentech, Inc. Anna M. Demetriades was an employee of Genentech, Inc. during development of this manuscript. Laurent Kodjikian is a consultant for AbbVie, Alimera, Bayer, Horus, Novartis, Roche, and Thea. Jennifer I. Lim is a consultant for Aura, Cognition, Eyenuk, Luxa, Opthea, Quark, Roche\/Genentech, Inc., Santen, Unity, and Viridian; has received financial support from Aldeyra, Chengdu, Janssen, NGM Bio, Regeneron, Roche\/Genentech, Inc., and Stealth; and is a grant recipient from Iveric Bio and Novartis. Philippe Margaron is an employee of F. Hoffmann La Roche Ltd. Jordi M. Mon\u00e9s has received research funds from Apellis, Ionis Pharmaceuticals, Iveric Bio, Janssen, Kodiak Sciences, Novartis, Reneuron, and Roche; is a consultant for Annexon, Apellis, Cellcure, Iveric Bio, Lineage Cell Therapeutics, Maculogix, Novartis, PerceiveBio, Reneuron, and Roche; and has equity in EyeBio, Iveric Bio, Notal Vision, and Perceive. Tunde Peto is an advisor for Alimera, Astellas, Bayer, Heidelberg, Novartis, Optomed, OPTOS, Oxurion, and Roche. Federico Ricci is an advisor for AbbVie, Allergan, Apellis, Astellas, Bayer, Biogen, MSD, Novartis, Regeneron, and Roche. Matthias R\u00fcth is an employee of F. Hoffmann La Roche Ltd. Rishi P. Singh is a consultant for Alcon, AsclepiX, Bausch and Lomb, Genentech, Inc., Gyroscope, Novartis, and Regeneron, and has received research sponsorship from NGM Bio. Ivaylo Stoilov is an employee of Genentech, Inc. Balakumar Swaminathan was an employee of Genentech Inc. during development of this manuscript. Jeffrey R. Willis is an employee of Genentech, Inc. Peter D. Westenskow is an employee of F. Hoffmann-La Roche Ltd.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}