Characterization of the glycosylation profile of erythropoiesis-stimulating agents (ESAs) and impact on potency

Abstract

To evaluate the impact of glycosylation of Chinese Hamster Ovary (CHO) cell produced erythropoiesis-stimulating agents (ESAs) on in vivo efficacy, epoetin glycoforms were fractionated and characterized. A comprehensive series of biochemical, in vitro bio-functional analyses and in vivo potency assays were conducted to better understand the relationship of structure to function of epoetin glycoforms. The hyper-glycosylated ESA darbepoetin alfa was also assessed to understand the range of in vivo potency response. Results demonstrate a strong link between sialylation or antennary structure, but not between N-acetyllactosamine repeat number and in vivo potency. Results for darbepoetin as compared to epoetin also confirm an inverse relationship between in vivo potency and potency measured using in vitro methods.

Keywords: Biosimilar(s); Cellular Receptor; Glycosylation; Hepatic Clearance; In Vitro/In Vivo (IVIVC) Correlation(s).