Switching to Biosimilar Epoetin Alfa Is Noninferior to Continuing Epogen When Using a Dosing Algorithm

Two pivotal studies of biosimilar epoetin alfa (Retacrit) versus its reference (Epogen) in patients undergoing hemodialysis have shown that the biosimilar and the originator have comparable safety and efficacy. In the phase 3b PIEDA (Phase 3b Investigation of Erythropoietin Drugs Using a Specified Dosing Algorithm) study, investigators sought to further investigate how switching from the reference to the biosimilar affects maintenance of hemoglobin levels when using an erythropoiesis-stimulating agent (ESA) dosing algorithm.

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The 24-week, open-label PIEDA study was conducted in 418 patients with anemia and chronic kidney disease at 46 Fresenius Medical Care North America (FMCNA) dialysis centers. The investigators used a computerized dosing algorithm that was originally developed for the reference program and is used in real-world practice in the FMCNA dialysis centers. The study’s primary endpoint was the proportion of the time that patients’ hemoglobin levels were 9 g/dL to 11 g/dL during the final 8 weeks of the study.

Patients were randomized to either continue treatment with the reference product (n = 206) or switch to the biosimilar (n = 212), and were treated for 24 weeks. Throughout the treatment period, the dose of epoetin alfa was adjusted using the algorithm, though the algorithm’s dose recommendation could be overridden at the provider’s discretion.

Data from 178 patients in the switch arm and 173 patients in the reference arm were included in the primary endpoint analysis. The estimated proportion of time that patients had hemoglobin levels in the target range was 61.9% (95% CI, 57.5%-66.2%) in the switch arm and 63.3% (95% CI, 58.7%-67.7%) in the reference arm. The estimated difference in proportions between the arms was —1.4% (95% CI, –7.6%-4.9%). The lower bound of the 95% CI was greater than the prespecified noninferiority margin of –12.5%, demonstrating noninferiority of switching to the biosimilar versus remaining on the reference.

Analysis of the change from baseline in weekly mean ESA doses over the final 8 weeks was based on 180 patients in the switch arm and 174 patients in the reference arm. The least squares mean change from baseline was —1861.8 (standard deviation [SD], 563.5) units per week for the switch arm and –799.8 (SD, 573.1) units per week for the reference arm, a difference that was not statistically significant.

In the final 8 weeks of treatment, the majority of patients had hemoglobin levels in the range of 10 g/dL to 11 g/dL in both the switch arm (56.7%) and the reference arm (53.2%) arm.

A total of 418 patients (61.5%) reported at least 1 treatment-emergent adverse event (AE). Of these patients, 135 were in the switch arm and 122 were in the reference arm. The most frequently reported AEs were dyspnea, falls, and nausea. The proportion of patients who had serious AEs was 31.1% in each arm. Twelve patients in each arm died during the study period, while 68 patients in the switch arm and 63 patients in the reference arm were hospitalized. There were no notable changes from baseline in laboratory parameters and vital signs between arms.

The authors concluded that switching to biosimilar epoetin alfa was noninferior to continued treatment with the reference in maintaining hemoglobin levels in patients with anemia and chronic kidney disease who are managed on hemodialysis when both treatments are dosed using an algorithm.

Reference

Thadhani R, Guilatco R, Hymes J, Maddux FW, Ahuja A. Switching from epoetin alfa (Epogen) to epoetin alfa-epbs (Retacrit) using a dosing algorithm: a randomized, non-inferiority study in adults on hemodialysis. Am J Nephrol. 2018;48(3): 214-224. doi: 10.1159/000492621.