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

Lancet. 2022 Feb 19;399(10326):729-740. doi: 10.1016/S0140-6736(22)00010-1. Epub 2022 Jan 24.


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 with ClinicalTrials.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.

Funding: F Hoffmann-La Roche.

Publication types

  • Clinical Trial, Phase III
  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors* / administration & dosage
  • Angiogenesis Inhibitors* / adverse effects
  • Angiopoietin-2* / antagonists & inhibitors
  • Antibodies, Bispecific* / administration & dosage
  • Antibodies, Bispecific* / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Intravitreal Injections
  • Macular Degeneration* / diagnosis
  • Macular Degeneration* / drug therapy
  • Male
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A* / antagonists & inhibitors
  • Visual Acuity / drug effects


  • aflibercept
  • Angiogenesis Inhibitors
  • Angiopoietin-2
  • ANGPT2 protein, human
  • Antibodies, Bispecific
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • VEGFA protein, human
  • faricimab

Associated data

  • ClinicalTrials.gov/NCT03823300
  • ClinicalTrials.gov/NCT03823287