Faricimab reduces macular leakage vs aflibercept in patients with DME

Abstract

Purpose : Increased vascular permeability is a hallmark feature of diabetic macular edema (DME). In preclinical mouse models, dual angiopoietin-2 (Ang-2)/vascular endothelial growth factor A (VEGF-A) inhibition was associated with greater vascular leakage reductions versus Ang-2 or VEGF-A inhibition alone, suggesting synergistic actions of Ang-2 and VEGF-A. This analysis evaluated if dual Ang-2/VEGF-A inhibition with faricimab improves macular leakage over VEGF-A inhibition alone with aflibercept in patients with DME.

Methods : YOSEMITE (NCT03622580) and RHINE (NCT03622593) were identical trials evaluating the efficacy and safety of 6.0-mg faricimab versus 2.0-mg aflibercept in patients with center-involving DME. Patients were randomized 1:1:1 to faricimab every 8 weeks (Q8W), faricimab according to a personalized treat-and-extend–based regimen (T&E), or aflibercept Q8W. This analysis included data from the first 16 weeks of the trials (matched dosing phase) in which all patients received assigned study drug Q4W. The faricimab Q8W and T&E arms were pooled as they received the same dosing regimen during this period. Outcomes included macular leakage area and the proportion of patients with minimal to no macular leakage (0–1 mm²).

Results : Data from the pooled YOSEMITE/RHINE trials included 1216 patients in the pooled faricimab arms and 593 patients in the aflibercept arms. Median baseline macular leakage area was similar in the faricimab (24.58 mm²) and aflibercept arms (25.64 mm²). At week 16, median macular leakage area was significantly lower in the faricimab versus aflibercept arm (3.59 vs 7.62 mm², respectively; P < 0.0001) (Fig 1). A significantly greater proportion of patients receiving faricimab (28.4%) demonstrated minimal to no leakage at week 16 compared with those receiving aflibercept (15.2%; P < 0.0001).

Conclusions : In patients with DME, dual Ang-2/VEGF-A inhibition with faricimab resulted in a greater reduction in macular leakage and a larger proportion of patients achieving minimal to no leakage versus aflibercept. These findings suggest that dual Ang-2/VEGF inhibition provides greater vascular stability, which may contribute to the faster fluid resolution and extended durability observed with faricimab versus aflibercept in YOSEMITE/RHINE.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.