3 Early clinical trial data clearly demonstrated the benefits of ranibizumab however, the mandatory monthly intravitreal injections place a significant burden on patients and healthcare systems. 3 Ranibizumab (Lucentis) is the first approved recombinant humanized monoclonal antibody fragment that can block human VEGFA and improve visual acuity in patients with wAMD. 3 In the last decade, several intravitreal anti-VEGF drugs have been introduced consequently, previously unachievable improvements in vision have been observed in patients with wAMD. High expression of vascular endothelial growth factor A (VEGFA) is a major factor that contributes to disease pathogenesis by stimulating choroidal neovascularization, resulting in the leakage of blood and fluid into the macula. Through neuropilin 1 binding, IDB0062 can improve the efficacy and accelerate the onset of pharmacological action in the posterior segment, which is targeted for macular degeneration, thereby improving drug responsiveness in drug-resistant patients.Ĭonsidering its novel mechanism of action, IDB0062 may help in controlling resistance to conventional anti–vascular endothelial growth factor drugs in clinical settings. In the monkey intravitreal pharmacokinetic study, IDB0062 improved drug distribution in the retina compared with ranibizumab, confirming the accelerated onset of pharmacological action when IDB0062 is injected in the vitreous humor. In addition, IDB0062 showed non-inferior efficacy compared with aflibercept in vivo despite the low selectivity for mouse vascular endothelial growth factor A. IDB0062 effectively inhibited not only vascular endothelial growth factor A in vitro but also placenta growth factor 2, vascular endothelial growth factor B, and platelet-derived growth factor BB, which induce vascular endothelial growth factor A–independent angiogenesis. To evaluate the ocular distribution of IDB0062, we intravitreally administered IDB0062 and ranibizumab to cynomolgus monkeys and measured the retinal drug levels. The in vivo efficacy of IDB0062 was determined using mouse choroidal neovascularization and oxygen-induced retinopathy models. We compared the in vitro activity of IDB0062 and conventional drugs using cell proliferation, wound healing, and Transwell assays. To overcome this drawback, we developed the novel recombinant dual-targeting antibody fragment IDB0062, which is comprised of the anti–vascular endothelial growth factor A Fab and neuropilin 1-targeting peptide, and we assessed its properties. Repeated administration of anti–vascular endothelial growth factor drugs to treat age-related macular degeneration leads to resistance.
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