Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies

Jay B Wish, Marcelo G Rocha, Nancy E Martin, Christian Russel D Reyes, Steven Fishbane, Mark T Smith, George Nassar, Jay B Wish, Marcelo G Rocha, Nancy E Martin, Christian Russel D Reyes, Steven Fishbane, Mark T Smith, George Nassar

Abstract

Rationale & objective: Epoetin alfa-epbx is a biosimilar to the reference product, epoetin alfa. We compare the safety of epoetin alfa-epbx versus epoetin alfa based on a pooled analysis of findings from 2 randomized, double-blind, comparative clinical studies, and report new data for the long-term safety of epoetin alfa-epbx.

Study design: Pooled analyses of previously conducted studies.

Setting & participants: Hemodialysis patients with anemia.

Interventions: Data from patients who received 1 or more subcutaneous or intravenous doses of study drug were integrated across route of administration in combined randomized groups (epoetin alfa-epbx, n = 423; epoetin alfa, n = 426). Data from patients who received 1 or more doses of epoetin alfa-epbx in either open-label extension trial were integrated across route of administration in a combined long-term safety studies group (n = 576).

Outcomes: Adverse events (AEs), immunogenicity, and other outcomes were assessed.

Results: Incidences of treatment-emergent AEs, serious AEs, and discontinuation of study drug treatment because of treatment-emergent AEs were similar between combined randomized epoetin alfa-epbx and epoetin alfa, which had mean treatment durations of 18.1 and 17.7 weeks, respectively. Incidences of treatment-emergent AEs, serious AEs, and discontinuation of study drug treatment because of treatment-emergent AEs were 86.5%, 39.4%, and 6.6%, respectively, for the combined long-term safety studies group, which had a mean treatment duration of 40.0 weeks. In total, 12 patients across the combined randomized groups (epoetin alfa-epbx, n = 5; epoetin alfa, n = 7) and 9 patients in the combined long-term safety studies group tested anti-recombinant human erythropoietin antibody positive in 1 or more visits during study conduct. No patient in any group developed neutralizing antibodies or pure red blood cell aplasia.

Limitations: Epoetin alfa comparator not included in the long-term safety studies, greater cumulative exposure to study drug for epoetin alfa-epbx, shorter follow-up in the randomized studies, and potential for selection bias among patients in the open-label long-term safety studies.

Conclusions: This analysis reinforces previous conclusions of similar safety profiles between epoetin alfa-epbx and epoetin alfa. Furthermore, epoetin alfa-epbx had no unexpected safety signals during long-term treatment.

Funding: This study was funded by Hospira Inc, which was acquired by Pfizer Inc in September 2015.

Trial registration: ClinicalTrials.gov EPOE-10-13 (NCT01473420); EPOE-10-01 (NCT01473407); EPOE-11-04 (NCT01628120); EPOE-11-03 (NCT01628107).

Keywords: Anemia; chronic kidney disease; epoetin alfa; epoetin alfa-epbx; hemodialysis; long-term; safety.

© 2019 Pfizer Inc. and the Author(s).

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Patient disposition. Study completion and study discontinuation rates for the combined randomized and combined open-label long-term safety study (LTSS) groups. aPatients were eligible for the open-label LTSSs, EPOE-11-04 and EPOE-11-03, if they received treatment and completed the required study assessments during the respective core studies: EPOE-10-13 maintenance period, up to and including week 16 study assessments; and EPOE-10-01 treatment period, up to and including week 24 study assessments. Patients who discontinued treatment before week 16 of the maintenance period in EPOE-10-13 and before week 24 of the treatment period in EPOE-10-01 were offered treatment with standard-of-care erythropoiesis-stimulating agents (ESAs) for the rest of the maintenance and treatment periods and were to complete the required week 16 (EPOE-10-13) or week 24 (EPOE-10-01) study assessments to be eligible for enrollment in the LTSS. Enrollment in the LTSS occurred within 28 days after completion of the maintenance period week 16 study assessments for the EPOE-10-13 core study and after completion of the treatment period week 24 study assessments for the EPOE-10-01 core study. Abbreviation: AE, adverse event.

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