Darbepoetin Alfa (Mylan EPD LLC)

Abstract:  Darbepoetin alfa (KRN321) is a novel molecule that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its 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. This multicenter, open‐label, single‐arm study of 72 patients with end stage renal failure on peritoneal dialysis (PD) evaluated the efficacy and safety of KRN321 administered intravenously with the dosing intervals extended to monthly. PD patients that were either rHuEPO‐naïve or rHuEPO‐receiving were enrolled. In rHuEPO‐naïve patients, the initial dose of KRN321 was 40 μg weekly by intravenous administration. For rHuEPO‐receiving patients, an initial regimen of fortnightly intravenous administration was given and the initial dose was based on the dose of rHuEPO used before switching to KRN321. After starting the study medication, the Hb concentration was maintained between 10.0 g/dL and 13.0 g/dL. In those patients whose Hb concentrations showed a stable time‐course, the dosing intervals of KRN321 were extended. The results suggest that it may be feasible to reduce the frequency of treatment to a monthly schedule, with an associated adjustment of dose, in most patients. Adverse events were observed in 67 of the 72 patients (93.1%, 267 events). Most of all the adverse events were reported in patients with chronic renal failure receiving conventional rHuEPO. No safety problems specific to KRN321 were noted. These results suggest that KRN321 could reduce of frequency of hospital visits for PD patients receiving erythropoietic therapy for renal anemia.

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 μg) 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.