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

Ophthalmology. 2024 Aug;131(8):914-926. doi: 10.1016/j.ophtha.2024.02.014. Epub 2024 Feb 19.

Abstract

Purpose: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A.

Design: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials.

Participants: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older.

Methods: Patients 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 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 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.

Results: Of 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.

Conclusions: Treat-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.

Keywords: Angiopoietin-2; Faricimab; Neovascular age-related macular degeneration; Vascular endothelial growth factor A; Vascular stability.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors* / administration & dosage
  • Angiogenesis Inhibitors* / therapeutic use
  • Angiopoietin-2* / antagonists & inhibitors
  • Antibodies, Bispecific* / administration & dosage
  • Antibodies, Bispecific* / adverse effects
  • Antibodies, Bispecific* / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Humans
  • Intravitreal Injections*
  • Male
  • Middle Aged
  • Receptors, Vascular Endothelial Growth Factor* / administration & dosage
  • Receptors, Vascular Endothelial Growth Factor* / antagonists & inhibitors
  • Recombinant Fusion Proteins* / administration & dosage
  • Recombinant Fusion Proteins* / adverse effects
  • Recombinant Fusion Proteins* / therapeutic use
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A* / antagonists & inhibitors
  • Visual Acuity* / physiology
  • Wet Macular Degeneration* / diagnosis
  • Wet Macular Degeneration* / drug therapy
  • Wet Macular Degeneration* / physiopathology

Substances

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

Associated data

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