Reduction in Pigment Epithelial Detachment Thickness with Faricimab versus Aflibercept 2 mg during Head-to-Head Dosing in TENAYA/LUCERNE

Summary

TENAYA LUCERNE post hoc: nAMD PED improved better with Vabysmo than Eylea 2mg.

Abstract

Purpose: To evaluate the effects of dual angiopoietin-2 (Ang-2)/VEGF-A pathway inhibition with faricimab versus VEGF pathway inhibition with aflibercept 2 mg on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD).

Design: TENAYA/LUCERNE (NCT03823287/NCT03823300) post hoc analysis.

Participants: Patients with treatment-naïve nAMD.

Methods: Patients were randomized 1:1 to faricimab 6 mg up to every 16 weeks (n = 665) after 4 initial every-4-week (Q4W) doses or aflibercept 2 mg every 8 weeks (n = 664) after 3 Q4W doses. Pigment epithelial detachment was defined as retinal pigment epithelium (RPE) elevation width ≥350 μm and graded as predominantly/purely serous (serous PED) or predominantly/only fibrovascular (fibrovascular PED). Large PED definition: thickness ≥125 μm.

Main outcome measures: Pigment epithelial detachment thickness change from baseline during initial 12-week head-to-head dosing, proportion of patients with serous PED at the end of head-to-head dosing, and time to first reduction of maximum PED thickness by 50%.

Results: Baseline PED characteristics were similar between arms. At week 12, the adjusted mean decrease from baseline in maximum PED thickness was greater with faricimab than aflibercept 2 mg in eyes with large (-119.1 [n = 500] vs. -101.4 μm [n = 496]; nominal P = 0.0028), serous (-136.1 [n = 128] vs. -108.2 μm [n = 114]; nominal P = 0.0147), and any type (-87.9 [n = 644] vs. -74.5 μm [n = 638]; nominal P = 0.0067) PED at baseline. The proportion of eyes with serous PED at baseline remaining serous at week 12 was lower with faricimab than aflibercept 2 mg (4.7% vs. 13.4%; nominal P = 0.0258). In eyes with large PED at baseline, the cumulative incidence of PEDs achieving time to first reduction of maximum PED thickness by 50% at week 12 was 35.3% with faricimab versus 25.7% with aflibercept 2 mg. The corresponding incidence in eyes with serous PED at baseline was 61.1% with faricimab versus 51.8% with aflibercept 2 mg. The incidence of RPE tears was low (faricimab, 2.9%; aflibercept 2 mg, 1.5%).

Conclusions: In TENAYA/LUCERNE, dual Ang-2/VEGF-A inhibition with faricimab elicited greater improvements in PED outcomes versus aflibercept 2 mg during head-to-head dosing. These findings are consistent with the greater drying of retinal fluid with faricimab during head-to-head dosing, which may allow for rapid treatment interval extension.