Darbepoetin alfa effectively maintains hemoglobin concentrations at extended dose intervals relative to intravenous rHuEPO in Japanese dialysis patients

Abstract

Darbepoetin alfa (KRN321) is a novel molecule that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its three-fold longer half-life and greater biological activity than recombinant human erythropoietin (rHuEPO), KRN321 maintains an effective hemoglobin (Hb) level at extended dose intervals compared with rHuEPO. In this multicenter, open-label study, 513 dialysis patients maintained on stable rHuEPO therapy were switched to KRN321 at extended dose intervals. Those receiving rHuEPO two (n = 144, 28.1%) or three times (n = 305, 59.5%) per week were switched to KRN321 once per week, and those receiving rHuEPO once per week (n = 64, 12.5%) were switched to KRN321 once every two weeks. The doses of KRN321 (10-120 microg) were titrated to maintain Hb concentrations at 10-13 g/dL and, if possible, within 11-12 g/dL for up to 52 weeks. If the Hb concentration remained between 10.5 and 12 g/dL, conversion of the dosing frequency from once per week to once every two weeks was allowed. Hemoglobin concentrations were maintained regardless of the dosing interval. The percentage of patients with Hb values within 11-12 g/dL was 23.6% at week 0, 41.3% at week 7, 46.1%-51.9% between weeks 11 and 22 and 45.6% at week 52. KRN321 was well tolerated and the safety profile was consistent with previous trials conducted for KRN321. KRN321, when administered at extended dose intervals, is well tolerated and effective Hb concentrations are attained in Japanese hemodialysis patients.