Epoetin Delta, Erythropoietin Produced in a Human Cell Line, Is as Effective as Epoetin Alfa in the Treatment of Anemia.

Abstract

Epoetin therapy for anemia in patients with chronic kidney disease (CKD) is widespread and effective. Currently available erythropoietins are produced in Chinese hamster ovary (CHO) cell lines. Epoetin delta (Dynepo®, Shire plc) is the only erythropoietin synthesized in a human cell line. We report data from a 24-week, double-blind, active-comparator study, followed by a 28 week open-label phase, designed to test whether epoetin delta was as effective as epoetin alfa in the treatment of anemia in patients receiving hemodialysis. Patients with hemoglobin levels of 9.6–12.4 g/dL who had been receiving epoetin therapy for at least 90 days were eligible for entry to the study. Patients were randomized to epoetin delta or epoetin alfa in a 3:1 ratio with the first dose of study medication identical to the last dose the patient received before entering the study. Subsequent dosing was adjusted according to a predefined algorithm to maintain hemoglobin within the target range of 10–12 g/dL. Efficacy was evaluated on the basis of weekly determinations of hematological parameters (hemoglobin, hematocrit, red blood cell [RBC] and reticulocyte count). The primary efficacy endpoint was average hemoglobin over Weeks 12, 16, 20 and 24 and to demonstrate that the difference in hemoglobin levels between the two groups was less than 1g/dL (90% CI contained within the range -1 to 1). Other key efficacy measures included the percentage of hemoglobin levels > 10g/dL and hematocrit levels > 30% and profiles of hematological parameters from baseline to Week 52. From the randomized population, 555 patients received epoetin delta and 191 received epoetin alfa. 583 finished the 24-week double-blind phase and all these patients passed into the open-label phase to be treated with epoetin delta. Adjusted average hemoglobin over Weeks 12–24 was 11.57 g/dL for the epoetin delta group and 11.56 g/dL for the epoetin alfa group. The difference between the groups was 0.01g/dL with both 90% CI (-0.13; 0.15) and 95% CI (-0.16; 0.17) within the predefined acceptable range of -1 to 1 g/dL demonstrating equivalence between the agents. 89.5 % of patients receiving epoetin delta had hemoglobin levels > 10 g/dL compared with 91.5% of patients receiving epoetin alfa. Average hemoglobin levels were maintained in the target range until the end of the study with no need to increase mean dose. Overall, treatment with epoetin delta at a mean dose of 63.7 IU/kg maintained hemoglobin levels at an average value of 11.31 g/dL over Weeks 12 through to the end of the study. In the double-blind phase the overall incidence of adverse events was similar between the study groups and at levels expected given the baseline characteristics of the study population. Hypotension, upper respiratory infection, muscle cramps and headache were the most commonly reported events overall and the levels were similar between the groups. Adverse events considered possibly related to treatment occurred in 11.6% of patients receiving epoetin delta compared with 8.4% of patients receiving epoetin alfa. No patient in this study developed neutralizing anti-erythropoietin antibodies to either epoetin alfa or epoetin delta. Epoetin delta was demonstrated to be as effective as epoetin alfa for maintenance of hemoglobin levels in CKD patients requiring hemodialysis. Control of hemoglobin level was maintained over 52 weeks without the need to increase average dose and epoetin delta was well tolerated for up to one year of exposure.