Preclinical safety and pharmacology of Hematide, a peptidic erythropoiesis stimulating agent (ESA), in rats and monkeys.

The pharmacology, toxicokinetics, and safety of Hematide, a synthetic peptidic erythropoiesis-stimulating agent (ESA), were characterized. Hematide was given intravenously (0, 0.5, 5, and 50 mg/kg) weekly for five weeks with a 6- (rat) and 12-week (monkey) recovery period. The pharmacological action of Hematide resulted in polycythemia. Histopathology consistent with drug-induced exaggerated pharmacology was observed primarily in rats. Secondary sequelae resulting from pronounced polycythemia was considered the cause of deaths in rats and a single high-dose monkey. Toxicokinetic analysis indicated prolonged exposure. In conclusion, Hematide is a potent ESA and the safety and efficacy profile support clinical development.