Single ocular injection of a sustained-release anti-VEGF delivers 6 months pharmacokinetics and efficacy in a primate laser CNV model

Abstract 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 6 month 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 IC 50 than aflibercept in VEGF receptor binding assays (RBAs) and retaining activity upon release from microparticles over 12 months in vitro . Microparticles released functional dual dAb in rabbit and primate eyes over 6 months 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 6 months. Polymer breakdown and movement of microparticles in the eye may limit development of particle-based approaches for sustained release after IVT injection.