Dual-Pathway Inhibition with Faricimab: Differentiating Mechanisms in Retinal Vascular Diseases

This segment delves into the molecular and mechanistic distinctions between faricimab’s dual inhibition of VEGF-A and Ang-2 and aflibercept’s VEGF-only blockade. The discussion highlights the theoretical and practical implications of targeting Ang-2, a modulator of vascular stability through the TIE2 pathway. While VEGF remains the dominant pathogenic driver, Ang-2 inhibition may contribute additional benefits by stabilizing the vasculature and reducing leakage. Panelists debate whether faricimab’s clinical success stems from its dual mechanism or its higher molar dose and full-length antibody structure. They also touch on mixed evidence surrounding Ang-2 biology and the halted BURGUNDY port-delivery trial, which leaves questions about Ang-2’s independent therapeutic value. The conversation closes with forward-looking insights on biomarker-guided and sustained-delivery approaches, envisioning a future where VEGF and Ang-2 activity could be measured in real time to personalize dosing and improve long-term outcomes in retinal vascular diseases.