In 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).
