TENAYA and LUCERNE

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of the bispecific antibody, faricimab, which inhibits both angiopoietin-2 and vascular endothelial growth factor-A. DESIGN: TENAYA (NCT03823287) and LUCERNE (NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials across 271 sites worldwide. PARTICIPANTS: Treatment-naïve patients with neovascular age-related macular degeneration (nAMD) aged ≥ 50 years. METHODS: 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-based 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 on 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 in patients who received ≥ 1 dose of study treatment. RESULTS: Of 1326 patients treated across the trials, 1113 (83.9%) completed study treatment (n = 555 faricimab and n = 558 aflibercept). BCVA change from baseline at 2 years was comparable between faricimab and aflibercept in TENAYA (adjusted mean change 95% confidence interval (CI) +3.7 letters +2.1 to +5.4 and +3.3 letters +1.7 to +4.9, respectively; mean difference 95% CI 0.4 letters -1.9 to +2.8) and in LUCERNE (adjusted mean change 95% CI +5.0 letters +3.4 to +6.6 and +5.2 +3.6 to +6.8, respectively; mean difference 95% CI -0.2 letters -2.4 to +2.1). At week 112 in TENAYA and LUCERNE respectively, 59.0% and 66.9% achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2% achieved ≥ Q12W dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept in TENAYA (55.0% and 56.5% of patients) and LUCERNE (52.9% and 47.5% of patients) through week 112. CONCLUSIONS: Treat-and-extend-based faricimab treatment based on nAMD disease activity maintained vision gains through year 2 with most patients achieving extended dosing intervals.