Novel Glycosylated VEGF Decoy Receptor Fusion Protein, VEGF-Grab3 showed superior anti-angiogenic efficacy to Aflibercept (Eylea): a potential therapeutic agent for exudative Age-related macular degeneration (AMD)

Abstract

Purpose : To investigate the therapeutic potential for AMD, in vitro and in vivo efficacy, safety, and intraocular pharmacokinetics of a novel Glycosylated VEGF Decoy Receptor Fusion Protein, VEGF-Grab3 were compared with those of Aflibercept (Eylea, VEGF-Trap-Eye).

Methods : The binding affinity of drugs to VEGF and PlGF were assessed using a biacore assay. For the evaluation of in vivo anti-angiogenic efficacy, choroidal neovascularization (CNV) and oxygen induced retinopathy (OIR) mouse models were used. High dose (25µg/1µL) and low dose (2µg/1µL) of VEGF-Grab3 and Aflibercept were injected intravitreally in the right eyes. Ocular toxicity was evaluated up to 30 days and was compared between two drugs with histopathologic and electromicroscopic analysis of mouse eyeballs. Intraocular pharmacokinetics were also investigated using rabbit eyes.

Results : Affinity of VEGF-Grab3 to VEGF and PlGF was about 3-fold higher than Aflibercept. In vivo anti-angiogenic efficacy of VEGF-Grab3 was superior than Aflibercept for low dose administration while it was comparable for high dose administration. The mouse retina treated with the two drugs showed mildly increased müller cell activation and senescence of retinal pigment epithelial cells. However, no discernible ocular toxicity was observed. Intraocular pharmacokinetic profiles were similar between two drugs.

Conclusions : The new anti-VEGFR decoy protein, VEGF-Grab3 showed a superior therapeutic efficacy to Aflibercept with similar safety and pharmacokinetic profiles. Up to now, VEGF-grab3 is the most potent anti-VEGF agents that can be used for neovascular retinal diseases such as exudative AMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.