Author: Timothy Lai
Co-authors: Stephan Michels, Anna-Maria Demetriades, Carlos Quezada Ruiz, David Silverman, Jane Ives, Balakumar Swaminathan, Hugh Lin
Abstract
Purpose: Week 48 data from the phase 3 TENAYA/LUCERNE trials support the hypothesis that dual inhibition of angiopoietin-2 and vascular endothelial growth factor (VEGF)-A with faricimab, the first bispecific antibody designed for intraocular use, may promote vascular stability and durable efficacy beyond current anti-VEGF therapies for neovascular age-related macular degeneration (nAMD). Here we report pooled 48-week efficacy results by faricimab dosing interval cohort.Setting/Venue: TENAYA (NCT03823287) and LUCERNE (NCT03823300) were identical, randomised, double-masked, active comparator–controlled, 112-week, phase 3 trials of faricimab in nAMD.
Methods : Treatment-naïve patients (pooled N = 1329) were randomised 1:1 to faricimab 6.0 mg up to every 16 weeks (Q16W; n = 665) or aflibercept 2.0 mg Q8W (n = 664). After 4 initial Q4W doses, faricimab-treated patients received Q8W, Q12W or Q16W dosing throughout the maintenance phase, based on pre-specified central subfield thickness (CST) and best-corrected visual acuity (BCVA) disease activity criteria and presence of new macular hemorrhage, as determined by the investigator during clinical examination at weeks 20 and 24. The primary endpoint was change in BCVA from baseline averaged over weeks 40, 44 and 48. Secondary efficacy endpoints, including visual/anatomical outcomes, were assessed Q4W through week 48. This post hoc analysis evaluated efficacy outcomes by faricimab dosing interval cohort as determined during clinical examination visits.
Results: Faricimab resulted in similar visual acuity and anatomical outcomes compared with aflibercept at week 48. The proportions of faricimab-treated patients on the different dosing interval cohorts at week 48 were as follows: Q16W, 45%; Q12W, 34%; and Q8W, 21%. The baseline patient demographics were generally well balanced across faricimab dosing interval cohorts. All faricimab-treated cohorts showed sustained vision gains throughout the maintenance phase. There was a consistently high proportion of patients avoiding a ≥ 15-letter vision loss throughout the study in all faricimab dosing interval cohorts (at week 48: Q16W, 96%; Q12W, 95%; and Q8W, 92%). In all faricimab dosing interval cohorts, the rapid decreases in CST during the 4-month initiation phase were sustained throughout the maintenance phase, with similar reductions between cohorts through week 48. Patients on the extended Q16W dosing interval maintained CST reductions after the initiation phase, with minimal variations in CST.
Conclusion : Vision gains and disease control in TENAYA/LUCERNE were sustained in the maintenance phase in all faricimab dosing interval cohorts. Despite receiving only 2 faricimab injections during the maintenance phase per study design, the Q16W dosing cohort demonstrated prolonged disease control and meaningful and sustained visual acuity gains, supporting the durable efficacy reported in the primary analysis.