Ocular half-life of intravitreal biologics in humans and other species: meta-analysis and model-based prediction

Therapeutic antibodies administered intravitreally are the current standard of care to treat retinal diseases. The ocular half-life (t½) is a key determinant of the duration of target suppression. To support the development of novel, longer-acting drugs, a reliable determination of t½ is needed together with an improved understanding of the factors that influence it. A model-based meta-analysis was conducted in humans and nonclinical species (rat, rabbit, monkey, and pig) to determine consensus values for the ocular t½ of IgG antibodies and Fab fragments. Results from multiple literature and in-house pharmacokinetic studies are presented within a mechanistic framework that assumes diffusion-controlled drug elimination from the vitreous. Our analysis shows, both theoretically and experimentally, that the ocular t½ increases in direct proportion to the product of the hydrodynamic radius of the macromolecule (3.0 nm for Fab and 5.0 nm for IgG) and the square of the radius of the vitreous globe, which varies ...