Aflibercept and Faricimab Equipotently Restore Endothelial Barrier Function

Area of Science:

• Ophthalmology and Angiogenesis Research
• Endothelial Cell Biology
• Molecular Medicine

Background:

• Vascular endothelial growth factor (VEGF)-A165 is a key driver of pathological angiogenesis and vascular permeability.
• VEGF-A165-induced vascular permeability contributes to various ocular diseases.
• Aflibercept and faricimab are biologic agents targeting VEGF-A165, but their comparative efficacy in maintaining endothelial barrier integrity requires further elucidation.

Purpose of the Study:

• To conduct a head-to-head in vitro comparison of aflibercept and faricimab.
• To evaluate their biological effects on vascular endothelial growth factor (VEGF)-A165-induced vascular permeability.
• To assess their impact on endothelial cell-layer integrity and related molecular pathways.

Main Methods:

• Utilized a human umbilical vein endothelial cell (HUVEC) model exposed to VEGF-A165.
• Administered aflibercept or faricimab preventively or therapeutically.
• Measured cell-layer permeability using the xCELLigence platform, transcriptomic changes via RNA sequencing, and protein release via electrochemiluminescence immunoassay.

Main Results:

• Both aflibercept and faricimab prevented VEGF-A165-induced increases in HUVEC cell-layer permeability.
• In therapeutic settings, both drugs temporally improved endothelial barrier integrity.
• Aflibercept demonstrated non-inferiority to faricimab in both preventive and therapeutic scenarios.
• Both agents comparably downregulated VEGF-A165-induced angiogenesis-related genes and suppressed/reversed angiopoietin-2 (ANG2) and soluble Tie2 expression.

Conclusions:

• In vitro, additional angiopoietin-2 (ANG2) blockade by faricimab did not enhance endothelial barrier integrity beyond VEGF-A165 blockade by aflibercept.
• Aflibercept and faricimab exhibited comparable efficacy in maintaining or restoring endothelial barrier function.
• The primary mechanism for maintaining vascular integrity appears to be the inhibition of VEGF-A165 binding to its receptor.