KHK4951 + aflibercept

KHK4951 + aflibercept is a combination regimen currently being investigated for the treatment of neovascular (wet) age-related macular degeneration (nAMD). It consists of KHK4951, an investigational small molecule nano-crystalized eye drop formulation of tivozanib, and aflibercept, a recombinant fusion protein already approved for nAMD and other retinal vascular diseases. KHK4951 acts as a vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 tyrosine kinase inhibitor, inhibiting VEGF-driven pathological angiogenesis and vascular leakage in the retina. Aflibercept binds and neutralizes VEGF-A, VEGF-B, and placental growth factor, preventing their activation of receptors that drive abnormal blood vessel growth and leakage. In current phase 2 clinical trials for nAMD, patients receive a run-in period with aflibercept injections (standard of care), followed by KHK4951 eye drops, with aflibercept available as rescue therapy if needed[2][5].