Wish Jay B, Rocha Marcelo G, Martin Nancy E, Reyes Christian Russel D, Fishbane Steven, Smith Mark T, Nassar George
Indiana University, Indianapolis, IN.
Pfizer Inc, Lake Forest, IL.
Kidney Med. 2019 Aug 28;1(5):271-280. doi: 10.1016/j.xkme.2019.06.009. eCollection 2019 Sep-Oct.
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.
Pooled analyses of previously conducted studies.
SETTING & PARTICIPANTS: Hemodialysis patients with anemia.
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).
Adverse events (AEs), immunogenicity, and other outcomes were assessed.
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.
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.
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.
This study was funded by Hospira Inc, which was acquired by Pfizer Inc in September 2015.
ClinicalTrials.gov EPOE-10-13 (NCT01473420); EPOE-10-01 (NCT01473407); EPOE-11-04 (NCT01628120); EPOE-11-03 (NCT01628107).
聚乙二醇化促红细胞生成素α-epbx是参比产品促红细胞生成素α的生物类似药。我们基于两项随机、双盲、对照临床研究结果的汇总分析，比较了聚乙二醇化促红细胞生成素α-epbx与促红细胞生成素α的安全性，并报告了聚乙二醇化促红细胞生成素α-epbx长期安全性的新数据。
对先前进行的研究进行汇总分析。
贫血的血液透析患者。
将接受1次或更多次皮下或静脉注射研究药物的患者数据，按给药途径整合到联合随机分组中（聚乙二醇化促红细胞生成素α-epbx，n = 423；促红细胞生成素α，n = 426）。在两项开放标签扩展试验中接受1次或更多次聚乙二醇化促红细胞生成素α-epbx注射的患者数据，按给药途径整合到联合长期安全性研究组中（n = 576）。
评估不良事件（AE）、免疫原性和其他结果。
在联合随机分组的聚乙二醇化促红细胞生成素α-epbx和促红细胞生成素α之间，治疗中出现的AE、严重AE以及因治疗中出现的AE而停用研究药物治疗的发生率相似，其平均治疗持续时间分别为18.1周和17.7周。联合长期安全性研究组的治疗中出现的AE、严重AE以及因治疗中出现的AE而停用研究药物治疗的发生率分别为86.5%、39.4%和6.6%，其平均治疗持续时间为40.0周。在联合随机分组中，共有12例患者（聚乙二醇化促红细胞生成素α-epbx，n = 5；促红细胞生成素α，n = 7），联合长期安全性研究组中有9例患者在研究期间的1次或更多次访视中抗重组人促红细胞生成素抗体检测呈阳性。任何组中均无患者产生中和抗体或纯红细胞再生障碍性贫血。
长期安全性研究未纳入促红细胞生成素α对照品，聚乙二醇化促红细胞生成素α-epbx的研究药物累积暴露量更大，随机研究的随访时间较短，开放标签长期安全性研究中的患者存在选择偏倚的可能性。
该分析强化了先前关于聚乙二醇化促红细胞生成素α-epbx与促红细胞生成素α安全性相似的结论。此外，聚乙二醇化促红细胞生成素α-epbx在长期治疗期间没有意外的安全信号。
本研究由Hospira公司资助，该公司于2015年9月被辉瑞公司收购。
ClinicalTrials.gov EPOE-10-13（NCT01473420）；EPOE-10-01（NCT01473407）；EPOE-11-04（NCT01628120）；EPOE-11-03（NCT01628107）。
