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

PURPOSE: To compare anatomic biomarkers on spectral-domain OCT between faricimab, a dual angiopoietin-2 (Ang-2)/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 III 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; the proportion of eyes with an absence of intraretinal fluid (IRF), subretinal fluid, or both IRF and 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: In total, 1891 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 to 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 to 100 was 70% to 74% with faricimab Q8W, 61% to 65% with faricimab T&E, and 61% to 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 improvements in anatomic outcomes compared with aflibercept at key timepoints over the pooled YOSEMITE/RHINE trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.