Anatomic Control with Faricimab versus Aflibercept in the YOSEMITE/RHINE Trials in Diabetic Macular Edema.

Abstract

Purpose: To compare anatomic biomarkers on spectral-domain optical coherence tomography between faricimab, a dual angiopoietin-2 (Ang-2)/vascular endothelial growth factor-A (VEGF-A) inhibitor, and aflibercept in a pooled analysis of results from the YOSEMITE/RHINE trials in diabetic macular edema (DME).

Design: YOSEMITE/RHINE (NCT03622580/NCT03622593) were identical, randomized, double-masked, active comparator-controlled, 100-week phase 3 noninferiority 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 treat-and-extend (T&E), or aflibercept 2.0 mg Q8W for 100 weeks. The T&E up to every 16 weeks dosing regimen was based on central subfield thickness (CST) and best-corrected visual acuity changes.

Main outcome measures: Post hoc analyses comparing faricimab with aflibercept on CST change; proportion of eyes with an absence of intraretinal fluid (IRF), and/or subretinal fluid, or achieving a CST < 280 μm at key timepoints during the trials; time to first absence of IRF; and time to first achieving CST < 280 μm.

Results: One thousand eight hundred ninety-one patients were enrolled across YOSEMITE/RHINE (n = 632 faricimab Q8W; n = 632 faricimab T&E; n = 627 aflibercept). There were greater CST reductions from baseline with both faricimab dosing regimens compared with aflibercept over the 100 weeks (adjusted means and area-under-the-curve analysis). Higher proportions of eyes achieved an absence of IRF with faricimab Q8W (58-63%) and faricimab T&E (44-49%) versus aflibercept (36-41%) at weeks 92-100. In eyes with IRF at baseline, the median time to first absence of IRF was achieved 40 weeks earlier with faricimab versus aflibercept. The proportion of eyes achieving a CST < 280 μm at weeks 92-100 was 70-74% with faricimab Q8W, 61-65% with faricimab T&E, and 61-63% with aflibercept. In eyes with CST ≥ 280 μm at baseline, the median time to first instance of CST < 280 μm was achieved 16 weeks earlier with faricimab versus aflibercept.

Conclusions: Dual Ang-2/VEGF-A inhibition with faricimab resulted in greater and faster improvement in anatomic outcomes compared with aflibercept at key timepoints over the pooled YOSEMITE/RHINE trials.