Safety and Biosimilarity of ior®EPOCIM Compared with Eprex® Based on Toxicologic, Pharmacodynamic, and Pharmacokinetic Studies in the Sprague–Dawley Rat

ABSTRACT: This study examined the safety, pharmacodynamic (PD), and pharmacokinetic (PK) biosimilarity of the human recombinant erythropoietin (EPO) products ior®EPOCIM and Eprex®following a 28-day repeated intravenous dose administration in male and female Sprague–Dawley rats with a 14-day recovery period. Safety profiling was based on clinical observations, clinical pathology, and pathology findings for control rats dosed with vehicle and rats dosed either with 30, 300, and 600 I.U./kg of ior®EPOCIM or 600 I.U. of Eprex®. Adverse findings for both ior®EPOCIM and Eprex® were similar and were a consequence of thrombotic events (ulcerative skin lesions, swollen hock joints/lameness, stomach ulcers) and decreased body weight gains, all known adverse reactions to this class of drug in rats. With the exception of stomach ulcers, all other adverse findings were fully reversible. Neither drug stimulated the production of antidrug antibodies. As expected, ior®EPOCIM and Eprex® both increased reticulocyte, red blood cell, hemoglobin, and hematocrit levels in rats. The PK of EPO following dosing with ior®EPOCIM was well behaved and consistent with the literature. The results of this study imply that ior®EPOCIM and Eprex® had safety profiles, PD responses, and toxicokinetic profiles that were biosimilar. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3432–3441, 2014