Switching from Epoetin Alfa (Epogen®) to Epoetin Alfa-Epbx (Retacrit™) Using a Specified Dosing Algorithm: A Randomized, Non-Inferiority Study in Adults on Hemodialysis

Background: For patients with anemia undergoing hemodialysis, erythropoiesis-stimulating agents (ESAs) are typically dosed via precise algorithms. Using one such algorithm, we assessed the maintenance of hemoglobin levels in patients switched from epoetin alfa reference product (Epogen (R)) to epoetin alfa-epbx (Retacrit (TM); a biosimilar to US-licensed Epogen (R)/Procrit (R)). Methods: This randomized, open-label, non-inferiority study was conducted at Fresenius Medical Care North America (FMCNA) hemodialysis centers. Patients with anemia and chronic kidney disease undergoing maintenance hemodialysis and receiving routine intravenous (IV) Epogen (R) were randomized 1:1 to switch to IV Retacrit (TM) or continue standard-of-care (Epogen (R)) for 24 weeks, using analogous versions of the FMCNA ESA-dosing algorithm. The primary endpoint was the proportion of time patients' hemoglobin was 9-11 g/dL during weeks 17-24. Results: Of 432 randomized patients, 418 received treatment (Retacrit (TM), n = 212; standard-of-care, n = 206) and comprised the full analysis set. A similar proportion of patients discontinued from each arm. The proportion of time patients' hemoglobin was within the target range was 61.9% (95% CI 57.5-66.2) in the Retacrit (TM) arm and 63.3% (95% CI 58.7-67.7) in the standard-of-care arm. The difference in proportions between treatment arms was -1.4% (95% CI -7.6 to 4.9), and the lower bound of the confidence interval was within the pre-specified non-inferiority margin of -12.5%. There was no statistically significant difference between arms in the mean change from baseline in the weekly mean ESA dose during weeks 17-24, and no clinically relevant differences in safety outcomes. Conclusions: Switching to Retacrit (TM) was non-inferior to continuing Epogen (R) in maintaining hemoglobin levels in patients receiving hemodialysis, when both ESAs were dosed using a specified algorithm. (C) 2018 The Author(s) Published by S. Karger AG, Basel