TY - JOUR
T1 - Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD
T2 - Pooled Analyses of Randomized and Open-label Studies
AU - Wish, Jay B.
AU - Rocha, Marcelo G.
AU - Martin, Nancy E.
AU - Reyes, Christian Russel D.
AU - Fishbane, Steven
AU - Smith, Mark T.
AU - Nassar, George
N1 - Funding Information:
This study was funded by Hospira Inc, which was acquired by Pfizer Inc in September 2015. Funding for medical writing support was provided by Pfizer Inc. The study sponsor monitored patient data collected by the investigators for completeness and acceptability throughout the course of the studies, participated in study design and data collection for the integrated analysis, generated and validated statistical analyses, and reviewed the final author-approved version for intellectual property protection.
Funding Information:
Jay B. Wish, MD, Marcelo G. Rocha, MD, Nancy E. Martin, MD, PharmD, Christian Russel D. Reyes, MS, Steven Fishbane, MD, Mark T. Smith, MD, and George Nassar, MD. SF and NEM contributed to conception or design of the work; SF, GN, MTS, and JBW participated in data collection; and MGR, CRDR, and JBW contributed to data analysis. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This study was funded by Hospira Inc, which was acquired by Pfizer Inc in September 2015. Funding for medical writing support was provided by Pfizer Inc. The study sponsor monitored patient data collected by the investigators for completeness and acceptability throughout the course of the studies, participated in study design and data collection for the integrated analysis, generated and validated statistical analyses, and reviewed the final author-approved version for intellectual property protection. Dr Wish has received personal fees for an advisory board from Pfizer Inc. Dr Rocha and Mr Reyes are employees of and own stock or options in Pfizer Inc. Dr Martin was an employee of and held stock or options in Hospira Inc, a Pfizer company, at the time of study conduct. Dr Fishbane has received consultancy fees from Pfizer Inc and personal fees for advisory boards from Hospira Inc, Keryx Inc, AstraZeneca Inc, and Akebia Inc. Dr Smith has received personal fees for an advisory board from Keryx. Dr Nassar declares no conflicts of interest. Upon request and subject to certain criteria, conditions, and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual de-identified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines, and medical devices (1) for indications that have been approved in the USA and/or EU, or (2) in programs that have been terminated (ie, development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The deidentified participant data will be made available to researchers whose proposals meet the research criteria and other conditions and for which an exception does not apply through a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer. Medical writing support was provided by Elyse Smith, PhD, of Engage Scientific Solutions and was funded by Pfizer Inc. Received February 18, 2019. Evaluated by 2 external peer reviewers, with direct editorial input from the Statistical Editor and the Editor-in-Chief. Accepted in revised form June 9, 2019.
Publisher Copyright:
© 2019 Pfizer Inc. and the Author(s)
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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).
AB - 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).
KW - Anemia
KW - chronic kidney disease
KW - epoetin alfa
KW - epoetin alfa-epbx
KW - hemodialysis
KW - long-term
KW - safety
UR - http://www.scopus.com/inward/record.url?scp=85072702212&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072702212&partnerID=8YFLogxK
U2 - 10.1016/j.xkme.2019.06.009
DO - 10.1016/j.xkme.2019.06.009
M3 - Article
AN - SCOPUS:85072702212
VL - 1
SP - 271
EP - 280
JO - Kidney Medicine
JF - Kidney Medicine
SN - 2590-0595
IS - 5
ER -