1. 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
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Khanani, Arshad M, Kotecha, Aachal, Chang, Andrew, Chen, Shih-Jen, Chen, Youxin, Guymer, Robyn, Heier, Jeffrey S, Holz, Frank G, Iida, Tomohiro, Ives, Jane A, Lim, Jennifer I, Lin, Hugh, Michels, Stephan, Ruiz, Carlos Quezada, Schmidt-Erfurth, Ursula, Silverman, David, Singh, Rishi, Swaminathan, Balakumar, Willis, Jeffrey R, Tadayoni, Ramin, Investigators, TENAYA and LUCERNE, Abbey, Ashkan, Abdulaeva, Elmira, Abraham, Prema, Civera, Alfredo Adan, 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 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, Chao, Daniel, Chaudhry, Nauman, Chee, Caroline, Cheek, Andrew, 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, Vega, Alvaro Fernandez, Ferrone, Philip, Figueroa, Marta, Fine, Howard, Fineman, Mitchell, Fox, Gregory M, Francais, Catherine, and Franco, Pablo
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Macular Degeneration ,Aging ,Clinical Research ,Neurosciences ,Patient Safety ,Neurodegenerative ,Clinical Trials and Supportive Activities ,Eye Disease and Disorders of Vision ,6.1 Pharmaceuticals ,Eye ,Humans ,Male ,Female ,Visual Acuity ,Intravitreal Injections ,Double-Blind Method ,Antibodies ,Bispecific ,Aged ,Angiogenesis Inhibitors ,Vascular Endothelial Growth Factor A ,Middle Aged ,Recombinant Fusion Proteins ,Wet Macular Degeneration ,Receptors ,Vascular Endothelial Growth Factor ,Angiopoietin-2 ,Treatment Outcome ,Tomography ,Optical Coherence ,Follow-Up Studies ,Aged ,80 and over ,Fluorescein Angiography ,Dose-Response Relationship ,Drug ,TENAYA and LUCERNE Investigators ,Faricimab ,Neovascular age-related macular degeneration ,Vascular endothelial growth factor A ,Vascular stability ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
PurposeTo evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A.DesignTENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials.ParticipantsTreatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older.MethodsPatients 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 measuresEfficacy 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.ResultsOf 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.ConclusionsTreat-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.
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- 2024