A Matching-Adjusted Comparison of Faricimab and Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.

INTRODUCTION: Matching-adjusted network meta-analyses (NMAs) provide an established method to indirectly compare treatments across trials that share a common comparator. In this exploratory analysis, we conducted a matching-adjusted NMA to compare the efficacy of faricimab with aflibercept 8 mg for treatment of diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) via the common comparator of aflibercept 2 mg during the first 12 weeks of treatment when all agents are dosed equally.

METHODS: Weighting was applied to match patient populations from YOSEMITE/RHINE (NCT03622580/NCT03622593) and TENAYA/LUCERNE (NCT03823287/NCT03823300) based on their baseline characteristics to published aggregated baseline characteristics for PHOTON (NCT04429503) and PULSAR (NCT04423718), respectively. The matched populations were used to recalculate outcomes from faricimab trials and an NMA anchored to aflibercept 2 mg was conducted. The analysis focused on change in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters and central subfield thickness (CST) in µm during the first 12 weeks of treatment when dosing was every 4 weeks for all three agents. Results are expressed as mean difference in change in BCVA or CST for each aflibercept dose.

RESULTS: For nAMD, BCVA change was similar between faricimab and aflibercept 2 mg and 8 mg, whereas CST reduction was greater for faricimab versus aflibercept 8 mg (-17.0 µm; 95% credible interval [CrI], -25.0, -8.4) and 2 mg (-19.0 µm; 95% CrI, -24.0, -13.0). For DME, BCVA change from baseline at 12 weeks was similar between faricimab and aflibercept 2 mg and 8 mg, while CST reduction was greater for faricimab versus aflibercept 8 mg (-19.0 µm; 95% CrI, -35.0, -3.2) and 2 mg (-19.0 µm; 95% CrI, -27.0, -12.0).

CONCLUSION: This matching-adjusted NMA indicated that dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A inhibition with faricimab was associated with greater retinal drying during the matched-dosing phase in patients with nAMD and DME. Early dual pathway inhibition may therefore improve outcomes beyond anti-VEGF monotherapy.