Abstract
Purpose :
Dual inhibition of angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A with faricimab, the first bispecific antibody designed for intraocular use, may synergistically promote vascular stability and reduce treatment burden through extended durability in patients with neovascular age-related macular degeneration (nAMD). The phase 3 TENAYA and LUCERNE trials are designed to assess the efficacy, safety, and durability of faricimab compared with aflibercept in patients with nAMD. Here, we present the rationale for the clinical trial design.
Methods :
TENAYA (NCT03823287) and LUCERNE (NCT03823300) are identical, phase 3, randomized, double-masked, active comparator–controlled, 112-week studies of faricimab in nAMD. Treatment-naïve patients are randomized 1:1 to faricimab 6.0 mg up to every 16 weeks (Q16W) after 4 initial every-4-week (Q4W) doses or aflibercept 2.0 mg every 8 weeks (Q8W) after 3 initial Q4W doses. Based on disease activity assessments (prespecified anatomical and functional criteria, and investigator discretion) at weeks 20 and 24, patients in the faricimab arm are allocated to receive Q8W, every-12-week (Q12W), or Q16W dosing until week 60. Faricimab-treated patients then follow a personalized treatment interval (PTI), a protocol-driven treat-and-extend regimen with interval adjustment based on individualized treatment response as assessed by prespecified anatomical and functional criteria at study drug dosing visits, up to week 108.
Results :
The TENAYA and LUCERNE trials will evaluate the efficacy, safety, and durability of faricimab in patients with nAMD. The primary efficacy endpoint is change in best-corrected visual acuity from baseline averaged over weeks 40, 44, and 48. Secondary endpoints include the proportion of patients receiving faricimab Q16W, Q12W, and Q8W, and changes in anatomic outcomes; safety outcomes include the incidence and severity of adverse events. The PTI phase is designed to tailor treatment intervals according to patients’ needs, with individualized dosing up to Q16W, to reduce treatment burden while optimizing outcomes.
Conclusions :
The TENAYA and LUCERNE trials are ongoing global trials designed to evaluate the potential for dual Ang-2 and VEGF-A inhibition with faricimab to improve outcomes for patients with nAMD.
This is a 2021 ARVO Annual Meeting abstract.