A recent study evaluated the preclinical efficacy of VEGF-Grab, a novel VEGF candidate drug said to have a higher binding affinity to VEGF and placental growth factor (PlGF) than aflibercept, and found that it was comparable with aflibercept in in vivo antiangiogenic efficacy and superior in in vitro anti-VEGF activity. Clinical availability is still several years off, but these early results are promising as development moves forward.
The researchers noted that with current anti-VEGF agents, frequent retreatments are necessary, leading to a high economic burden; new angiogenesis-targeting agents that are equal to or better than conventional anti-VEGFs are needed. Aflibercept, a decoy receptor fusion protein, was the chosen comparison agent for VEGF-Grab—also a decoy receptor fusion protein—because it’s considered the most potent of the three currently available anti-VEGF agents, the other two of which are monoclonal antibodies.
The researchers determined the in vitro anti-VEGF efficacy of VEGF-Grab using VEGF-induced cell proliferation/migration and tube formation assays. They evaluated the in vivo antiangiogenic efficacy of intravitreal injection of VEGF-Grab and aflibercept in two angiogenesis models: mouse oxygen-induced retinopathy and rat laser-induced choroidal neovascularization.
In the in vitro model, VEGF-Grab demonstrated greater inhibition of VEGF-induced cell proliferation/migration than aflibercept and comparable inhibition of tube formation. In the in vivo oxygen-induced retinopathy model, VEGF-Grab showed comparable suppression of retinal neovascularization with aflibercept. The drug also had similar inhibition efficacy to aflibercept in the choroidal neovascularization model. In the mouse retina, there was no evidence of toxicity at seven and 30 days after the injection of either agent.
The researchers conclude that VEGF-Grab may be a potential candidate for AMD, macular edema, diabetic retinopathy and other VEGF-related eye disease treatments, and an alternative to aflibercept. “These results, together with the higher binding affinity to VEGF/PlGF suggested in the previous study, imply that VEGF-Grab offers greater potential for VEGF suppression than aflibercept.”
Hong HK, Park YJ, Kim DK, et al. Preclinical efficacy and safety of VEGF-Grab, a novel anti-VEGF drug, and its comparison to aflibercept. Retina. 2020;61:22.