Aflibercept (VEGF Trap-eye): the newest anti-VEGF drug
- Correspondence to Michael W Stewart, Associate Professor and Chairman, Department of Ophthalmology, Mayo Clinic Florida, 4500 San Pablo Rd., Jacksonville, FL 32224, USA; stewart.michael{at}mayo.edu
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Contributors MWS is the sole author and is responsible for conceptualising, researching and writing this manuscript.
The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology over the past 7 years has revolutionised the treatment of exudative age-related macular degeneration (AMD) and holds great promise for diabetic macular oedema, branch and central retinal vein occlusions, and retinopathy of prematurity. Each of the three available drugs (pegaptanib, bevacizumab and ranibizumab) was eagerly embraced by surgeons, but the subsequent clinical results have been mixed, and the regulatory hurdles, particularly those regarding off-label use of bevacizumab, have been challenging.
Into this mix enters aflibercept (VEGF Trap-eye (VTE); Eylea, Regeneron, Tarrytown, New York, USA), for which the US Food and Drug Administration granted approval for the treatment of subfoveal choroidal neovascularisation due to AMD on 18 November 2011. In contrast to the antibody-based VEGF binding strategy used by ranibizumab and bevacizumab, the VTE incorporates the second binding domain of the VEGFR-1 receptor and the third domain of the VEGFR-2 receptor.1 By fusing these extracellular protein sequences to the Fc segment of a human IgG backbone, in a manner similar to the rheumatoid arthritis drug etanercept, developers have created a chimeric protein with a very high VEGF binding affinity (Kd≈1 pM).2 Like ranibizumab and bevacizumab, the VTE binds all isomers of the VEGF-A family, and although the clinical significance of this is not yet known, it also binds VEGF-B and placental growth factor.
The approval application draws on the strengths of two concurrent AMD trials: the VIEW 1 trial, which enrolled 1217 patients in North American centres, and the VIEW 2 trial, which enrolled 1240 patients in South American, European, Asian and Australian centres. Each trial randomised patients among four treatment arms: monthly 0.5 mg VTE, monthly or bimonthly 2 mg VTE, and monthly …
