PMID- 38382813 OWN - NLM STAT- Publisher LR - 20240410 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) DP - 2024 Feb 19 TI - TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2. LID - S0161-6420(24)00134-9 [pii] LID - 10.1016/j.ophtha.2024.02.014 [doi] AB - PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Khanani, Arshad M AU - Khanani AM AD - Sierra Eye Associates and the University of Nevada, Reno, School of Medicine, Reno, Nevada. Electronic address: arshad.khanani@gmail.com. FAU - Kotecha, Aachal AU - Kotecha A AD - Roche Products, Ltd., Welwyn Garden City, United Kingdom. FAU - Chang, Andrew AU - Chang A AD - Sydney Retina Clinic, Sydney Eye Hospital, University of Sydney, and Discipline of Surgery, University of New South Wales, Sydney, Australia. FAU - Chen, Shih-Jen AU - Chen SJ AD - Department of Ophthalmology, Taipei Veterans General Hospital and National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Chen, Youxin AU - Chen Y AD - Department of Ophthalmology, Peking Union Medical College Hospital, Beijing, China. FAU - Guymer, Robyn AU - Guymer R AD - Center for Eye Research Australia, Royal Victorian Eye and Ear Hospital, and Department of Surgery, University of Melbourne, Melbourne, Australia. FAU - Heier, Jeffrey S AU - Heier JS AD - Ophthalmic Consultants of Boston, Boston, Massachusetts. FAU - Holz, Frank G AU - Holz FG AD - Department of Ophthalmology and GRADE Reading Center, University of Bonn, Bonn, Germany. FAU - Iida, Tomohiro AU - Iida T AD - Department of Ophthalmology, Tokyo Women's Medical University, Tokyo, Japan. FAU - Ives, Jane A AU - Ives JA AD - Roche Products, Ltd., Welwyn Garden City, United Kingdom. FAU - Lim, Jennifer I AU - Lim JI AD - Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois. FAU - Lin, Hugh AU - Lin H AD - Genentech, Inc., South San Francisco, California. FAU - Michels, Stephan AU - Michels S AD - Eye Clinic Zurich West, Zurich, Switzerland; Department of Ophthalmology, University of Zurich, Zurich, Switzerland. FAU - Quezada Ruiz, Carlos AU - Quezada Ruiz C AD - Genentech, Inc., South San Francisco, California. FAU - Schmidt-Erfurth, Ursula AU - Schmidt-Erfurth U AD - Department of Ophthalmology, Vienna Reading Center and Ophthalmic Image Analysis Group (OPTIMA), Medical University of Vienna, Vienna, Austria. FAU - Silverman, David AU - Silverman D AD - Roche Products, Ltd., Welwyn Garden City, United Kingdom. FAU - Singh, Rishi AU - Singh R AD - Cleveland Clinic Florida, Stuart, Florida. FAU - Swaminathan, Balakumar AU - Swaminathan B AD - F. Hoffmann-La Roche Ltd., Mississauga, Ontario, Canada. FAU - Willis, Jeffrey R AU - Willis JR AD - Genentech, Inc., South San Francisco, California. FAU - Tadayoni, Ramin AU - Tadayoni R AD - Universite Paris Cite, AP-HP, Lariboisiere, Saint Louis, Fondation Adolphe de Rothschild Hospitals, Paris, France. CN - TENAYA and LUCERNE Investigators LA - eng SI - ClinicalTrials.gov/NCT03823300 SI - ClinicalTrials.gov/NCT03823287 PT - Journal Article DEP - 20240219 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 SB - IM OTO - NOTNLM OT - Angiopoietin-2 OT - Faricimab OT - Neovascular age-related macular degeneration OT - Vascular endothelial growth factor A OT - Vascular stability FIR - Abbey, Ashkan IR - Abbey A FIR - Abdulaeva, Elmira IR - Abdulaeva E FIR - Abraham, Prema IR - Abraham P FIR - Adan Civera, Alfredo IR - Adan Civera A FIR - Agostini, Hansjurgen IR - Agostini H FIR - Alezzandrini, Arturo IR - Alezzandrini A FIR - Alfaro, Virgil IR - Alfaro V FIR - Almony, Arghavan IR - Almony A FIR - Altay, Lebriz IR - Altay L FIR - Amini, Payam IR - Amini P FIR - Antoszyk, Andrew IR - Antoszyk A FIR - Aradi, Etelka IR - Aradi E FIR - Arias, Luis IR - Arias L FIR - Arnold, Jennifer IR - Arnold J FIR - Asaria, Riaz IR - Asaria R FIR - Astakhov, Sergei IR - Astakhov S FIR - Astakhov, Yury IR - 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Vogt, Gabor IR - Vogt G FIR - Volker, Michael IR - Volker M FIR - Warrow, David IR - Warrow D FIR - Weber, Pamela IR - Weber P FIR - Wells, John A IR - Wells JA FIR - Wickremasinghe, Sanjeewa IR - Wickremasinghe S FIR - Wieland, Mark IR - Wieland M FIR - Williams, Geoff IR - Williams G FIR - Williams, Thomas IR - Williams T FIR - Wong, David IR - Wong D FIR - Wong, King IR - Wong K FIR - Wong, James IR - Wong J FIR - Wong, Ian IR - Wong I FIR - Wong, Robert IR - Wong R FIR - Wowra, Bogumil IR - Wowra B FIR - Wykoff, Charles C IR - Wykoff CC FIR - Yamashita, Ayana IR - Yamashita A FIR - Yasuda, Kanako IR - Yasuda K FIR - Yilmaz, Gursel IR - Yilmaz G FIR - Yiu, Glenn IR - Yiu G FIR - Yoneda, Ai IR - Yoneda A FIR - Yoon, Young Hee IR - Yoon YH FIR - Yoreh, Barak IR - Yoreh B FIR - Yu, Hyeong Gon IR - Yu HG FIR - Yu, Seung Young IR - Yu SY FIR - Yurieva, Tatiana IR - Yurieva T FIR - Zambrano, Alberto IR - Zambrano A FIR - Zatorska, Barbara IR - Zatorska B FIR - Zeolite, Carlos IR - Zeolite C EDAT- 2024/02/22 00:43 MHDA- 2024/02/22 00:43 CRDT- 2024/02/21 19:17 PHST- 2023/08/09 00:00 [received] PHST- 2024/02/12 00:00 [revised] PHST- 2024/02/13 00:00 [accepted] PHST- 2024/02/22 00:43 [pubmed] PHST- 2024/02/22 00:43 [medline] PHST- 2024/02/21 19:17 [entrez] AID - S0161-6420(24)00134-9 [pii] AID - 10.1016/j.ophtha.2024.02.014 [doi] PST - aheadofprint SO - Ophthalmology. 2024 Feb 19:S0161-6420(24)00134-9. doi: 10.1016/j.ophtha.2024.02.014.