Aflibercept

개요In November 2011, the U.S. FDA approved the recombinant fusion protein aflibercept, administered as an intravitreal injection, for the treatment of patients with neovascular (wet) age-related macular degeneration (AMD). Aflibercept differs from these agents in that it acts as a soluble decoy receptor that binds all VEGF isoforms more tightly than their native receptors, thereby diverting VEGF from its normal function. Aflibercept consists of a fusion of the second Ig domain of human VEGF receptor 1 and the third Ig domain of human VEGF receptor 2 fused to the constant region of (Fc) of human immunoglobulin G1. Aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kDa and glycoside molecular weight of 18 kDa. It is produced in recombinant Chinese hamster ovary (CHO) cells that overexpress the fusion protein. Aflibercept has subpicomolar affinity for VEGF-A (KD=0.66 pM for VEGF-A165 and 0.19 pM for VEGF-A121), the major driver of pathological angiogenesis and vascular leak in wet AMD.19 Ranibizumab and bevacizumab bind VEGF-A165 with lower affinity (KD=20.6 and 35.1 pM, respectively).