RESUMEN
Hematide is a synthetic peptide-based, pegylated erythropoiesis stimulating agent in clinical development for treatment of anemia. To support chronic clinical dosing requirements, a 9-month repeat dose IV monkey safety study was undertaken. Animals received 0, 0.2, 2 or 20 mg/kg hematide IV every three weeks for nine months followed by a 14-week recovery. Hematide administration was associated with time and dose-dependent polycythemia. Histological findings were related to exaggerated pharmacology that was secondary to the administration of an erythropoiesis stimulating agent to a normocythemic animal. In conclusion, these results support the use of repeated administration of hematide for the correction of anemia.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hematínicos/farmacología , Macaca fascicularis , Péptidos/farmacología , Polietilenglicoles/farmacología , Animales , Enfermedad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Eritropoyesis/efectos de los fármacos , Péptidos/efectos adversos , Polietilenglicoles/efectos adversosRESUMEN
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.