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d美国波士顿眼科咨询中心Jeffrey S Heier团队研究了玻璃体腔内注射faricimab治疗新生血管性年龄相关性黄斑变性的有效性、持久性和安全性。2022年1月24日，《柳叶刀》杂志发表了这一成果。

Faricimab是一种双特异性抗体，通过双重抑制血管生成素-2和血管内皮生长因子A发挥作用。研究组报道了两项3期临床试验的初步结果，这些试验评估了玻璃体腔内注射faricimab治疗新生血管性年龄相关性黄斑变性（nAMD）的疗效，最久每16周注射一次。

研究组在全球271个地点进行了一项随机、双盲、非劣效性试验，招募未接受治疗的50岁及以上nAMD患者，将患者按1：1随机分配，分别接受每8周玻璃体腔内注射faricimab 6.0 mg一次，并根据第20周和第24周方案定义的疾病活动评估，最多每16周注射一次；或每8周一次注射阿柏西普2.0 mg。

患者、研究人员、评估结果者和资助者均双盲。主要终点为在意向治疗人群中，在第40、44和48周（预先指定的非劣效边缘为4个字母）内，最佳矫正视力（BCVA）相对于基线的平均变化。安全性分析包括至少接受一剂研究治疗的患者。

在这两项试验中，共有1329名患者接受了随机分组。其中2019年2月19日至11月19日的试验中，faricimab组334例，阿柏西普组337例；2019年3月11日至11月1日的试验中，faricimab组331例，阿柏西普组327例。

第一个试验中，faricimab组与基线相比，经校正后BCVA平均改善5.8个字母，阿柏西普组平均改善5.1个字母；第二个试验中，两组较基线均改善6.6个字母，两个试验中faricimab的治疗效果均不逊于阿柏西普。Faricimab组和阿柏西普组的眼部不良事件发生率相差不大。

研究结果表明，每隔16周给予faricimab的视觉益处表明，它有可能在延长治疗间隔的同时保持疗效，从而减轻nAMD患者的治疗负担。

附：英文原文

Title: 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

Author: Jeffrey S Heier, Arshad M Khanani, Carlos Quezada Ruiz, Karen Basu, Philip J Ferrone, Christopher Brittain, Marta S Figueroa, Hugh Lin, Frank G Holz, Vaibhavi Patel, Timothy Y Y Lai, David Silverman, Carl Regillo, Balakumar Swaminathan, Francesco Viola, Chui Ming Gemmy Cheung, Tien Y Wong, Ashkan Abbey, Elmira Abdulaeva, Prema Abraham, Alfredo Adan Civera, Hansjurgen Agostini, Arturo Alezzandrini, Virgil Alfaro, Arghavan Almony, Lebriz Altay, Payam Amini, Andrew Antoszyk, Etelka Aradi, Luis Arias, Jennifer Arnold, Riaz Asaria, Sergei Astakhov, Yury Astakhov, Carl C. Awh, Chandra Balaratnasingam, Sanjiv Banerjee, Caroline Baumal, Matthias Becker, Rubens Belfort, Galina Bratko, William Jr. Z Bridges, Jamin Brown, David M. Brown, Maria Budzinskaya, Sylvia Buffet, Stuart Burgess, Iksoo Byon, Carlo Cagini, Jorge Calzada, Stone Cameron, Peter Campochiaro, John Carlson, Angela Carneiro, Clement Chan, Emmanuel Chang, Andrew Chang, Daniel Chao, Nauman Chaudhry, Caroline Chee, Andrew Cheek, Shih-Jen Chen, San-Ni Chen, Gemmy Cheung, Saradha Chexal, Mark Chittum, David Chow, Abosede Cole, Brian Connolly, Pierre Loic Cornut, Stephen Couvillion, Carl Danzig, Vesselin Daskalov, Amr Dessouki, Francois Devin, Michael Dollin, Rosa Dolz, Louise Downey, Richard Dreyer, Pravin Dugel, David Eichenbaum, Bora Eldem, Robert Engstrom, Joan Josep Escobar, Nicole Eter, David W. Faber, Naomi Falk, Leonard Feiner, Alvaro Fernandez Vega, Philip Ferrone, Marta Figueroa, Howard Fine, Mitchell Fineman, Gregory M. Fox, Catherine Francais, Pablo Franco, Samantha Fraser-Bell, Nicholas Fung, Federico Furno Sola, Richard Gale, Alfredo Garcia-Layana, Alfredo Garcia-Layana, Julie Gasperini, Maciej Gawecki, Faruque Ghanchi, Manjot Gill, Michel Giunta, David Glaser, Michaella Goldstein, Francisco Gomez Ulla, Fumi Gomi, Victor Gonzalez, Jordan Graff, Sunil Gupta, Rainer Guthoff, Robyn Guymer, Anton Haas, Robert Hampton, Katja Hatz, Ken Hayashi, Jeffrey Heier, Ewa Herba, Vrinda Hershberger, Patrick Higgins, Nancy Holekamp, Shigeru Honda, James Howard, Allen Hu, Stephen Huddleston

Issue&Volume: 2022-01-24

Abstract:

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 withClinicalTrials.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.

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

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00010-1/fulltext

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