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

Heier, J. S.; Khanani, A. M.; Quezada Ruiz, C.; Basu, K.; Ferrone, P. J.; Brittain, C.; Figueroa, M. S.; Lin, H.; Holz, F. G.; Patel, V.; Lai, T. Y. Y.; Silverman, D.; Regillo, C.; Swaminathan, B.; Viola, F.; Cheung, C. M. G.; Wong, T. Y.; Abbey, A.; Abdulaeva, E.; Abraham, P.; Adan Civera, A.; Agostini, H.; Alezzandrini, A.; Alfaro, V.; Almony, A.; Altay, L.; Amini, P.; Antoszyk, A.; Aradi, E.; Arias, L.; Arnold, J.; Asaria, R.; Astakhov, S.; Astakhov, Y.; Awh, C. C.; Balaratnasingam, C.; Banerjee, S.; Baumal, C.; Becker, M.; Belfort, R.; Bratko, G.; Bridges, W. Z.; Brown, J.; Brown, D. M.; Budzinskaya, M.; Buffet, S.; Burgess, S.; Byon, I.; Cagini, C.; Calzada, J.; Cameron, S.; Campochiaro, P.; Carlson, J.; Carneiro, A.; Chan, C.; Chang, E.; Chang, A.; Chao, D.; Chaudhry, N.; Chee, C.; Cheek, A.; Chen, S. -J.; Chen, S. -N.; Cheung, G.; Chexal, S.; Chittum, M.; Chow, D.; Cole, A.; Connolly, B.; Cornut, P. L.; Couvillion, S.; Danzig, C.; Daskalov, V.; Dessouki, A.; Devin, F.; Dollin, M.; Dolz, R.; Downey, L.; Dreyer, R.; Dugel, P.; Eichenbaum, D.; Eldem, B.; Engstrom, R.; Escobar, J. J.; Eter, N.; Faber, D. W.; Falk, N.; Feiner, L.; Fernandez Vega, A.; Ferrone, P.; Figueroa, M.; Fine, H.; Fineman, M.; Fox, G. M.; Francais, C.; Franco, P.; Fraser-Bell, S.; Fung, N.; Furno Sola, F.; Gale, R.; Garcia-Layana, A.; Gasperini, J.; Gawecki, M.; Ghanchi, F.; Gill, M.; Giunta, M.; Glaser, D.; Goldstein, M.; Gomez Ulla, F.; Gomi, F.; Gonzalez, V.; Graff, J.; Gupta, S.; Guthoff, R.; Guymer, R.; Haas, A.; Hampton, R.; Hatz, K.; Hayashi, K.; Heier, J.; Herba, E.; Hershberger, V.; Higgins, P.; Holekamp, N.; Honda, S.; Howard, J.; Hu, A.; Huddleston, S.; Iida, T.; Imaizumi, H.; Ito, Y.; Ito, Y.; Itty, S.; Javey, G.; Javid, C.; Kaga, T.; Kaluzny, J.; Kang, S. W.; Kapoor, K.; Karabas, L.; Kawasaki, T.; Kelty, P.; Kerenyi, A.; Khanani, A.; Khoramnia, R.; Khurana, R.; Kimura, K.; Klein-Mascia, K.; Kobayashi, N.; Kodjikian, L.; Koizumi, H.; Kokame, G.; Kulikov, A.; Kwong, H.; Kwun, R.; Lai, T.; Lai, C. -C.; Lalonde, L.; Lanzetta, P.; Larsen, M.; Lavina, A.; Lee, W. K.; Lee, J. E.; Lee, S.; Levy, J.; Lindsell, L.; Liu, M.; London, N.; Lotery, A.; Lozano Rechy, D.; Luckie, A.; Maberley, D.; Maeno, T.; Mahmood, S.; Makkouk, F.; Marcus, D.; Margherio, A.; Masse, H.; Matsubara, H.; Maturi, R.; Mehta, S.; Menon, G.; Mentes, J.; Michels, M.; Mitamura, Y.; Mitchell, P.; Mohamed, Q.; Mones, J.; Montemayor Lobo, R.; Montero, J.; Moore, J.; Mori, R.; Morori-Katz, H.; Mukherjee, R.; Murata, T.; Muzyka-Wozniak, M.; Nardi, M.; Narendran, N.; Nicolo, M.; Nielsen, J.; Nishimura, T.; Noda, K.; Nowinska, A.; Oh, H.; Ohr, M.; Okada, A.; Oleksy, P.; Ono, S.; Ozdek, S.; Ozturk, B.; Pablo, L.; Park, K. H.; Parke, D. W.; Parravano, M. C.; Patel, P.; Patel, A.; Patel, S.; Patel, S.; Pauleikhoff, D.; Pearce, I.; Pearlman, J.; Petkova, I.; Pieramici, D.; Pozdeyeva, N.; Qureshi, J.; Raczynska, D.; Ramirez Estudillo, J.; Rathod, R.; Razavi, H.; Reilly, G.; Ricci, F.; Rich, R.; Romanowska-Dixon, B.; Rosenblatt, I.; Ruiz Moreno, J. M.; Sacu, S.; Saedon, H.; Saeed, U.; Sagong, M.; Sakamoto, T.; Sandhu, S.; Sararols, L.; Saravia, M.; Schadlu, R.; Schlottmann, P.; Sekiryu, T.; Seres, A.; Sermet, F.; Shah, S.; Shah, R.; Shah, A.; Sheidow, T.; Sheth, V.; Shiragami, C.; Sikorski, B.; Silva, R.; Singerman, L.; Sisk, R.; Sorensen, T. L.; Souied, E.; Spinak, D. -J.; Staurenghi, G.; Steinmetz, R.; Stoller, G.; Stoltz, R.; Suan, E.; Suner, I.; Suzanne, Y.; Tadayoni, R.; Takahashi, K.; Takayama, K.; Taleb, A.; Talks, J.; Terasaki, H.; Thompson, J.; Toth-Molnar, E.; Tran, K.; Tuli, R.; Uchiyama, E.; Vajas, A.; Van Lith-Verhoeven, J.; Varsanyi, B.; Virgili, G.; Vogt, G.; Volker, M.; Warrow, D.; Weber, P.; Wells, J. A.; Wickremasinghe, S.; Wieland, M.; Williams, G.; Williams, T.; Wong, D.; Wong, K.; Wong, J.; Wong, I.; Wong, R.; Wowra, B.; Wykoff, C. C.; Yamashita, A.; Yasuda, K.; Yilmaz, G.; Yiu, G.; Yoneda, A.; Yoon, Y. H.; Yoreh, B.; Yu, H.; S. Y., Yu; Yurieva, T.; Zambrano, A.; Zatorska, B.; Zeolite, C.

doi:10.1016/S0140-6736(22)00010-1

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.