Single ocular injection of a sustained-release anti-VEGF delivers 6 months pharmacokinetics and efficacy in a primate laser CNV model
نویسندگان
چکیده
A potent anti-vascular endothelial growth factor (VEGF) biologic and a compatible delivery system were co-evaluated for protection against wet age-related macular degeneration (AMD) over a 6month period following a single intravitreal (IVT) injection. The anti-VEGF molecule is dimeric, containing two different anti-VEGF domain antibodies (dAb) attached to a human IgG1 Fc region: a dual dAb. The delivery system is based on microparticles of PolyActive™ hydrogel co-polymer. The molecule was evaluated both in vitro for potency against VEGF and in ocular VEGF-driven efficacy models in vivo. The dual dAb is highly potent, showing a lower IC50 than aflibercept in VEGF receptor binding assays (RBAs) and retaining activity upon release from microparticles over 12months in vitro. Microparticles released functional dual dAb in rabbit and primate eyes over 6months at sufficient levels to protect Cynomolgus against laser-induced grade IV choroidal neovascularisation (CNV). This demonstrates proof of concept for delivery of an anti-VEGF molecule within a sustained-release system, showing protection in a pre-clinical primate model of wet AMD over 6months. Polymer breakdown and movement of microparticles in the eye may limit development of particle-based approaches for sustained release after IVT injection.
منابع مشابه
Ocular microparticle formulations for 6-month delivery of anti-VEGF.
Dr. Judah Folkman’s groundbreaking research in the fields of angiogenesis and vascular biology has been translated into successful medicines in the eye to treat disorders, such as wet age-related macular degeneration (AMD) and diabetic retinopathy. Although preceded by the ill-fated aptamer, pegaptanib (Macugen), the development of ranibizumab (Lucentis), the first protein-based vascular endoth...
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