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Vascular endothelial growth factor decoy receptor fusion protein (Aflibercept)

Target: Aflibercept
Molecular classification: Other (recombinant fusion protein), Decoy receptor (soluble receptor fusion protein)

Overview

Aflibercept is a recombinant fusion protein consisting of the extracellular ligand-binding domains of human vascular endothelial growth factor receptor 1 (VEGFR-1) and 2 (VEGFR-2), fused to the Fc portion of human IgG1. It acts as a high-affinity soluble decoy receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF), blocking their interaction with cellular VEGF receptors. By sequestering these ligands, aflibercept inhibits pathologic angiogenesis and vascular permeability in conditions such as neovascular (wet) age-related macular degeneration, diabetic macular edema, and metastatic colorectal cancer.

Other names: EyleaZaltrapVEGR TrapVEGF Trap-EyeZiv-afliberceptAflibercept-jbvf (Yesafili, biosimilar)Aflibercept-yszy (Opuviz, biosimilar)

Mechanism of action

Binds VEGF-A, VEGF-B, and PlGF with high affinity, preventing them from activating VEGF receptors (VEGFR-1 and VEGFR-2) on endothelial cells. Inhibits ligand-induced receptor dimerization and downstream signal transduction, suppressing angiogenesis and vascular permeability.

Biological functions

Binds and sequesters VEGF-A, VEGF-B, and PlGF, specifically blocking their interaction with endogenous VEGF receptorsInhibits angiogenesis and vascular permeability by blocking VEGF signaling

Disease associations

Cancer (metastatic colorectal cancer)Ophthalmologic diseases: neovascular (wet) age-related macular degeneration (AMD)Ophthalmologic diseases: diabetic macular edema (DME)Ophthalmologic diseases: macular edema following retinal vein occlusion (RVO)Ophthalmologic diseases: diabetic retinopathyOphthalmologic diseases: retinopathy of prematurity

Safety considerations

Intraocular: endophthalmitis, retinal detachment, increased intraocular pressureSystemic: arterial thromboembolic events, hypertension, proteinuria (notable primarily with systemic use in cancer)Hypersensitivity reactions and risk of systemic VEGF blockade effects (wound healing impairment, hemorrhage)

Interacting drugs

FOLFIRI regimen (fluorouracil, leucovorin, irinotecan) for metastatic colorectal cancer

Biomarkers

Increased ocular or systemic VEGF-A/PlGF levels (as an indicator for likely efficacy, but not established as companion diagnostic for aflibercept)Optical coherence tomography (OCT) imaging for retinal fluidVisual acuity changes, as clinical endpointsBiomarkers for selection/monitoring are mainly clinical or imaging-based rather than molecular

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