VEGF-A / VEGF-B / Placental Growth Factor (PlGF)

Class

Recombinant fusion protein (VEGF Trap — extracellular domains of VEGFR-1 and VEGFR-2 fused to a human IgG1 Fc region) — aflibercept, brand Eylea/Eylea HD

Pathway

Acts as a soluble decoy receptor, binding VEGF-A, VEGF-B, and PlGF with higher affinity than their native receptors, thereby blocking receptor activation and downstream angiogenic/vascular-permeability signaling

VEGF (vascular endothelial growth factor) family members—VEGF-A, VEGF-B, and placental growth factor (PlGF)—are signaling proteins that drive the growth of new blood vessels (angiogenesis) and increase the permeability of existing vessels. In several eye diseases, these proteins are locally overproduced, causing fluid accumulation, hemorrhage, and vision-threatening tissue damage. Aflibercept is a fusion protein built from the ligand-binding portions of two VEGF receptors, VEGFR-1 and VEGFR-2, joined to the constant region of a human antibody. This construct functions as a soluble decoy receptor, binding circulating VEGF-A, VEGF-B, and PlGF before they can engage their natural receptors on vascular endothelial cells, thereby blocking the downstream signaling that promotes vessel proliferation and leakiness. By neutralizing three related ligands rather than one, this approach addresses redundancy within the pathway, since PlGF and VEGF-B can activate overlapping receptor systems and sustain disease activity independent of VEGF-A alone. This mechanism is broadly relevant wherever pathological angiogenesis and vascular leakage underlie tissue injury, most notably in retinal and choroidal vascular disorders, though the same biological logic extends to other conditions driven by excessive VEGF pathway activity.