ATC Group: S01LA Antineovascularisation agents

Aflibercept, also known as VEGF TRAP in the scientific literature, is a recombinant fusion protein consisting of VEGF-binding portions from the extracellular domains of human VEGF receptors 1 and 2 fused to the Fc portion of the human IgG1. Aflibercept blocks the activation of VEGF receptors and the proliferation of endothelial cells, thereby inhibiting the growth of new vessels that supply tumours with oxygen and nutrients.

Anecortave, a synthetic cortisone, has been shown to have antiangiogenic properties that have been established in multiple experimental models of angiogenesis. Anecortave is under investigation to treat exudative age-related macular degeneration (AMD). Although similar in chemical structure to the corticosteroid hydrocortisone acetate, it possesses no glucocorticoid activity.

Bevacizumab binds to vascular endothelial growth factor (VEGF), the key driver of vasculogenesis and angiogenesis, and thereby inhibits the binding of VEGF to its receptors, Flt-1 (VEGFR-1) and KDR (VEGFR-2), on the surface of endothelial cells. Neutralising the biological activity of VEGF regresses the vascularisation of tumours, normalises remaining tumour vasculature, and inhibits the formation of new tumour vasculature, thereby inhibiting tumour growth.

Brolucizumab is a humanised monoclonal single chain Fv (scFv) antibody fragment with a molecular weight of ~26 kDa. Brolucizumab binds with high affinity to VEGF-A isoforms, thereby preventing binding of VEGF-A to its receptors VEGFR-1 and VEGFR-2. By inhibiting VEGF-A binding, brolucizumab suppresses endothelial cell proliferation, thereby reducing pathological neovascularisation and decreasing vascular permeability.

Faricimab is a humanised bispecific immunoglobulin G1 (IgG1) antibody that acts through inhibition of two distinct pathways by neutralisation of both angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A). By dual inhibition of Ang-2 and VEGF-A, faricimab reduces vascular permeability and inflammation, inhibits pathological angiogenesis and restores vascular stability.

Pegaptanib is a pegylated modified oligonucleotide that binds with high specificity and affinity to extracellular Vascular Endothelial Growth Factor (VEGF165) inhibiting its activity. VEGF is a secreted protein that induces angiogenesis, vascular permeability and inflammation, all of which are thought to contribute to the progression of the neovascular (wet) form of AMD.

Ranibizumab is a humanised recombinant monoclonal antibody fragment targeted against human vascular endothelial growth factor A (VEGF-A). It binds with high affinity to the VEGF-A isoforms, thereby preventing binding of VEGF-A to its receptors VEGFR-1 and VEGFR-2. Binding of VEGF-A to its receptors leads to endothelial cell proliferation and neovascularisation, as well as vascular leakage, all of which are thought to contribute to the progression of the neovascular form of age-related macular degeneration, pathologic myopia and CNV or to visual impairment caused by either diabetic macular oedema or macular oedema secondary to RVO in adults and retinopathy of prematurity in preterm infants.

Verteporfin, also referred to as benzoporphyrin derivative monoacids (BPD-MA) consists of a 1:1 mixture of the equally active regioisomers BPD-MA_C and BPD-MA_D. It produces cytotoxic agents only when activated by light in the presence of oxygen. The selectivity of PDT using verteporfin is based, in addition to the localised light exposure, on selective and rapid uptake and retention of verteporfin by rapidly proliferating cells including the endothelium of choroidal neovasculature.