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

PURPOSE

To evaluate if dual angiopoietin-2 (Ang-2)/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 III 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 (T&E)-based regimen, 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 every 4 weeks (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 mm) and high macular leakage (defined as macular leakage area ≥10 mm) 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 mm) and aflibercept arms (25.6 mm). At week 16, median macular leakage area was 3.6 mm with faricimab versus 7.6 mm 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.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.