Resolution of Angiographic Macular Leakage with Faricimab Versus Aflibercept in Patients with Diabetic Macular Edema in YOSEMITE/RHINE

Abstract

Purpose: To evaluate if dual angiopoietin-2 (Ang-2)/vascular endothelial growth factor-A (VEGF-A) inhibition with faricimab resulted in greater macular leakage resolution versus aflibercept in patients with diabetic macular edema (DME).

Design: Post hoc analysis of macular leakage assessments prespecified in the YOSEMITE/RHINE (NCT03622580/NCT03622593) phase 3 trials.

Participants: Adults with visual acuity loss due to center-involving DME.

Methods: Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg according to a personalized treat-and-extend-based regimen (T&E), or aflibercept 2.0 mg Q8W. This analysis included the first 16 weeks (head-to-head dosing period) when all patients received assigned study drug Q4W; patients were assessed 4 weeks after receiving 4 doses of assigned study drug Q4W.

Main outcome measures: Macular leakage area on fluorescein angiography assessed by a reading center; proportion of patients with resolution of macular leakage (defined as macular leakage area 0-1 mm²) and high macular leakage (defined as macular leakage area ≥ 10 mm²) at baseline and week 16; and the proportion of faricimab T&E patients receiving Q16W dosing at week 52 among those with resolution of and high macular leakage at week 16.

Results: Among patients with macular leakage data available at baseline, there were 1216 patients in the pooled faricimab (Q8W + T&E) arms and 593 patients in the aflibercept arm. Baseline median macular leakage area was similar between the faricimab (24.6 mm²) and aflibercept arms (25.6 mm²). At week 16, median macular leakage area was 3.6 mm² with faricimab versus 7.6 mm² with aflibercept (nominal P < 0.0001). More faricimab-treated patients (28%) achieved resolution of macular leakage versus aflibercept at week 16 (15%; nominal P < 0.0001). In the faricimab T&E arm, 63% of patients with resolution of macular leakage and 45% of patients with high macular leakage at week 16 achieved Q16W dosing at week 52 (nominal P < 0.01).

Conclusions: Faricimab demonstrated greater macular leakage resolution versus aflibercept during head-to-head dosing. These findings suggest that dual Ang-2/VEGF-A inhibition promotes vascular stability beyond VEGF inhibition alone, supporting faricimab's potential to offer greater disease control and extend durability for patients with DME.

Keywords: Angiopoietin-2; Diabetic macular edema; Faricimab; Macular Leakage; Vascular endothelial growth factor-A.