Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Issue 10326 (19th February 2022)

• Record Type: Journal Article
• Authors: Heier, Jeffrey S; Khanani, Arshad M; Quezada Ruiz, Carlos; Basu, Karen; Ferrone, Philip J; Brittain, Christopher; Figueroa, Marta S; Lin, Hugh; Holz, Frank G; Patel, Vaibhavi; Lai, Timothy Y Y; Silverman, David; Regillo, Carl; Swaminathan, Balakumar; Viola, Francesco; Cheung, Chui Ming Gemmy; Wong, Tien Y; Abbey, Ashkan; Abdulaeva, Elmira; Abraham, Prema; Adan Civera, Alfredo; Agostini, Hansjurgen; Alezzandrini, Arturo; Alfaro, Virgil; Almony, Arghavan; Altay, Lebriz; Amini, Payam; Antoszyk, Andrew; Aradi, Etelka; Arias, Luis; Arnold, Jennifer; Asaria, Riaz; Astakhov, Sergei; Astakhov, Yury; Awh, Carl C.; Balaratnasingam, Chandra; Banerjee, Sanjiv; Baumal, Caroline; Becker, Matthias; Belfort, Rubens; Bratko, Galina; Bridges, William Jr. Z; Brown, Jamin; Brown, David M.; Budzinskaya, Maria; Buffet, Sylvia; Burgess, Stuart; Byon, Iksoo; Cagini, Carlo; Calzada, Jorge; Cameron, Stone; Campochiaro, Peter; Carlson, John; Carneiro, Angela; Chan, Clement; Chang, Emmanuel; Chang, Andrew; Chao, Daniel; Chaudhry, Nauman; Chee, Caroline; Cheek, Andrew; Chen, Shih-Jen; Chen, San-Ni; Cheung, Gemmy; Chexal, Saradha; Chittum, Mark; Chow, David; Cole, Abosede; Connolly, Brian; Cornut, Pierre Loic; Couvillion, Stephen; Danzig, Carl; Daskalov, Vesselin; Dessouki, Amr; Devin, Francois; Dollin, Michael; Dolz, Rosa; Downey, Louise; Dreyer, Richard; Dugel, Pravin; Eichenbaum, David; Eldem, Bora; Engstrom, Robert; Escobar, Joan Josep; Eter, Nicole; Faber, David W.; Falk, Naomi; Feiner, Leonard; Fernandez Vega, Alvaro; Ferrone, Philip; Figueroa, Marta; Fine, Howard; Fineman, Mitchell; Fox, Gregory M.; Francais, Catherine; Franco, Pablo; Fraser-Bell, Samantha; Fung, Nicholas; Furno Sola, Federico; Gale, Richard; Garcia-Layana, Alfredo; Garcia-Layana, Alfredo; Gasperini, Julie; Gawecki, Maciej; Ghanchi, Faruque; Gill, Manjot; Giunta, Michel; Glaser, David; Goldstein, Michaella; Gomez Ulla, Francisco; Gomi, Fumi; Gonzalez, Victor; Graff, Jordan; Gupta, Sunil; Guthoff, Rainer; Guymer, Robyn; Haas, Anton; Hampton, Robert; Hatz, Katja; Hayashi, Ken; Heier, Jeffrey; Herba, Ewa; Hershberger, Vrinda; Higgins, Patrick; Holekamp, Nancy; Honda, Shigeru; Howard, James; Hu, Allen; Huddleston, Stephen; Iida, Tomohiro; Imaizumi, Hiroko; Ito, Yasuo; Ito, Yasuki; Itty, Sujit; Javey, Golnaz; Javid, Cameron; Kaga, Tatsushi; Kaluzny, Jakub; Kang, Se Woong; Kapoor, Kapil; Karabas, Levent; Kawasaki, Tsutomu; Kelty, Patrick; Kerenyi, Agnes; Khanani, Arshad; Khoramnia, Ramin; Khurana, Rahul; Kimura, Kazuhiro; Klein-Mascia, Kendra; Kobayashi, Namie; Kodjikian, Laurent; Koizumi, Hideki; Kokame, Gregg; Kulikov, Alexey; Kwong, Henry; Kwun, Robert; Lai, Timothy; Lai, Chi-Chun; Lalonde, Laurent; Lanzetta, Paolo; Larsen, Michael; Lavina, Adrian; Lee, Won Ki; Lee, ji Eun; Lee, Seong; Levy, Jaime; Lindsell, Lucas; Liu, Mimi; London, Nikolas; Lotery, Andrew; Lozano Rechy, David; Luckie, Alan; Maberley, David; Maeno, Takatoshi; Mahmood, Sajjad; Makkouk, Fuad; Marcus, Dennis; Margherio, Alan; Masse, Helene; Matsubara, Hisashi; Maturi, Raj; Mehta, Sonia; Menon, Geeta; Mentes, Jale; Michels, Mark; Mitamura, Yoshinori; Mitchell, Paul; Mohamed, Quresh; Mones, Jordi; Montemayor Lobo, Rodrigo; Montero, Javier; Moore, Jeffrey; Mori, Ryusaburo; Morori-Katz, Haia; Mukherjee, Raj; Murata, Toshinori; Muzyka-Wozniak, Maria; Nardi, Marco; Narendran, Niro; Nicolo, Massimo; Nielsen, Jared; Nishimura, Tetsuya; Noda, Kousuke; Nowinska, Anna; Oh, Hideyasu; Ohr, Matthew; Okada, Annabelle; Oleksy, Piotr; Ono, Shinji; Ozdek, Sengul; Ozturk, Banu; Pablo, Luis; Park, Kyu Hyung; Parke, D. Wilki; Parravano, Maria Cristina; Patel, Praveen; Patel, Apurva; Patel, Sunil; Patel, Sugat; Pauleikhoff, Daniel; Pearce, Ian; Pearlman, Joel; Petkova, Iva; Pieramici, Dante; Pozdeyeva, Nadezhda; Qureshi, Jawad; Raczynska, Dorota; Ramirez Estudillo, Juan; Rathod, Rajiv; Razavi, Hessam; Regillo, Carl; Reilly, Gayatri; Ricci, Federico; Rich, Ryan; Romanowska-Dixon, Bożena; Rosenblatt, Irit; Ruiz Moreno, Jose Maria; Sacu, Stefan; Saedon, Habiba; Saeed, Usman; Sagong, Min; Sakamoto, Taiji; Sandhu, Sukhpal; Sararols, Laura; Saravia, Mario; Schadlu, Ramin; Schlottmann, Patricio; Sekiryu, Tetsuju; Seres, András; Sermet, Figen; Shah, Sumit; Shah, Rohan; Shah, Ankur; Sheidow, Thomas; Sheth, Veeral; Shiragami, Chieko; Sikorski, Bartosz; Silva, Rufino; Singerman, Lawrence; Sisk, Robert; Sisk, Robert; Sørensen, Torben L.; Souied, Eric; Spinak, David-J; Staurenghi, Giovanni; Steinmetz, Robert; Stoller, Glenn; Stoltz, Robert; Suan, Eric; Suner, Ivan; Suzanne, Yzer; Tadayoni, Ramin; Takahashi, Kanji; Takayama, Kei; Taleb, Alexandre; Talks, James; Terasaki, Hiroko; Thompson, John; Toth-Molnar, Edit; Tran, Khoi; Tuli, Raman; Uchiyama, Eduardo; Vajas, Attila; Van Lith-Verhoeven, Janneke; Varsanyi, Balazs; Viola, Francesco; Virgili, Gianni; Vogt, Gábor; Völker, Michael; Warrow, David; Weber, Pamela; Wells, John A.; Wickremasinghe, Sanjeewa; Wieland, Mark; Williams, Geoff; Williams, Thomas; Wong, David; Wong, King; Wong, James; Wong, Ian; Wong, Robert; Wowra, Bogumil; Wykoff, Charles C.; Yamashita, Ayana; Yasuda, Kanako; Yilmaz, Gursel; Yiu, Glenn; Yoneda, Ai; Yoon, Young Hee; Yoreh, Barak; Yu, HyeongGon; Yu, Seung Young; Yurieva, Tatiana; Zambrano, Alberto; Zatorska, Barbara; Zeolite, Carlos;
• Is Part Of: Lancet. Volume 399:Issue 10326(2022)
• Page Start: 729
• Page End: 740
• Publication Date: 2022-02-19
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Medicine; Electronic journals; Periodicals; 610.5
• DOI: 10.1016/S0140-6736(22)00010-1
• Languages: English
• ISSNs: 0140-6736

Abstract

Summary: Background: Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD). Methods: TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300 ). Findings: Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [−1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [–1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]). Interpretation: Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD. Funding: F Hoffmann-La Roche.