Comparability of biosimilar romiplostim with originator: Protein characterization, animal pharmacodynamics and pharmacokinetics

The results of preclinical studies of romiplostim analogue GP40141 are presented. The effect of a cell proliferation, phosphorylation of the TPO receptor and JAK2 phosphorylation were studied in the presence of romiplostim and in the presence of GP40141 in a cell line of mice (Mus musculus) lymphoblasts with stable expression of human TPO receptor 32D-hTPOR clone 63. Binding to the TPO receptor and to the neonatal Fc receptor (FcRn) was examined for both romiplostim and the developed analogue. In Sprague-Dawley rats, the dynamics of platelet count after the administration of romiplostim or GP40141 were determined. The pharmacokinetics of romiplostim and GP40141, as well as the dynamics of platelet count, were studied in cynomolgus monkeys. The serum concentrations of romiplostim were determined using a modified colorimetric enzyme-linked immunosorbent assay (ELISA). The data obtained allow us to assert the similarity of the biological action of Nplate® and GP40141.