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 - 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
SN - 2590-0595
VL - 1
SP - 271
EP - 280
JO - Kidney Medicine
JF - Kidney Medicine
IS - 5
ER -