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

Thadhani, Ravi
Guilatco, Ruffy
Hymes, Jeffrey
Maddux, Franklin W.
Ahuja, Ajay

^aDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
^bDivision of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
^cPfizer Essential Health, Clinical Development and Medical Affairs, Pfizer Inc., Makati City, Philippines
^dFresenius Medical Care North America, Waltham, Massachusetts, USA
^ePfizer Essential Health, Clinical Development and Medical Affairs, Pfizer Inc., Lake Forest, Illinois, USA

^*Ravi Thadhani, MD, MPH, Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (USA), E-Mail [email protected]

Received May 30, 2018; Accepted August 01, 2018; previously published online September 07, 2018

American Journal of Nephrology 48(3):p 214-224, September 2018. | DOI: 10.1159/000492621

Abstract

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®) to epoetin alfa-epbx (RetacritTM; a biosimilar to US-licensed Epogen®/Procrit®).

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® were randomized 1: 1 to switch to IV RetacritTM or continue standard-of-care (Epogen®) 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 (RetacritTM, 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 RetacritTM 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: