Predicting Aflibercept Local Exposure Using Ocular PBPK Model

This technical report presents a study on predicting the local exposure of aflibercept in humans through the use of an ocular physiologically based pharmacokinetic (O-PBPK) model. The study outlines the challenges faced by the pharmaceutical industry in developing both innovative and generic ophthalmic drug products. It details how O-PBPK models can provide insights into drug distribution across various eye tissues and serve as an alternative method for studying ocular pharmacokinetics and pharmacodynamics. The objective of this research is to demonstrate the application of a validated O-PBPK model, using preclinical data, to estimate clinical local exposure levels of aflibercept, a biologic therapy for Neovascular Age-Related Macular Degeneration. The findings indicate that the OCAT model effectively describes the concentrations of aflibercept in the aqueous humor, vitreous humor, and retina in rabbits, and adjustments made for human physiology allow for accurate predictions of systemic and ocular exposures in humans following intravitreal administration.