贝伐珠单抗生物类似药 MYL-1402O 与 EU-贝伐珠单抗和 US-贝伐珠单抗的药代动力学研究。
A pharmacokinetics study of proposed bevacizumab biosimilar MYL-1402O vs EU-bevacizumab and US-bevacizumab.
机构信息
Viatris Inc, Morgantown, WV, USA.
PRA Health Sciences, Groningen, The Netherlands.
出版信息
J Cancer Res Clin Oncol. 2022 Feb;148(2):487-496. doi: 10.1007/s00432-021-03628-0. Epub 2021 Apr 17.
PURPOSE
Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor-specific angiogenesis in some cancers. MYL-1402O is a proposed bevacizumab biosimilar.
METHODS
The primary objective of this single-center, randomized, double-blind, three-arm, parallel-group, phase 1 study in healthy male volunteers was to evaluate bioequivalence of MYL-1402O to EU and US-reference bevacizumab, and EU-reference bevacizumab to US-reference bevacizumab. The primary pharmacokinetic parameter was area under the serum concentration-time curve from 0 extrapolated to infinity (AUC). Pharmacokinetic parameters were analyzed using general linear models of analysis of variance. Secondary endpoints included safety and tolerability.
RESULTS
Of 111 enrolled subjects, 110 were included in the pharmacokinetic analysis (MYL-1402O, n = 37; EU-reference bevacizumab, n = 36; US-reference bevacizumab, n = 37). Bioequivalence was demonstrated between MYL-1402O and EU-reference bevacizumab, MYL-1402O and US-reference bevacizumab, and between EU- and US-reference bevacizumab where least squares mean ratios of AUC were close to 1, and 90% CIs were within the equivalence range (0.80-1.25). Secondary pharmacokinetic parameters (AUC from 0 to time of last quantifiable concentration [AUC], peak serum concentration [C], time to C, elimination rate constant, and elimination half-life) were also comparable, with 90% CIs for ratios of AUC and C within 80-125%. Treatment-emergent adverse events were similar across all three treatment groups and were consistent with clinical data for bevacizumab.
CONCLUSION
MYL-1402O was well tolerated and demonstrated pharmacokinetic and safety profiles similar to EU-reference bevacizumab and US-reference bevacizumab in healthy male volunteers. No new significant safety issues emerged (ClinicalTrials.gov, NCT02469987; ClinicalTrialsRegister.eu EudraCT, 2014-005621-12; June 12, 2015).
目的
贝伐珠单抗是一种重组人源化单克隆抗体，可抑制某些癌症中血管内皮生长因子的特异性血管生成。Myl-1402O 是一种拟议的贝伐珠单抗生物类似药。
方法
这项在健康男性志愿者中进行的单中心、随机、双盲、三臂、平行组、I 期研究的主要目的是评估 MYL-1402O 与欧盟和美国参考贝伐珠单抗以及欧盟参考贝伐珠单抗与美国参考贝伐珠单抗的生物等效性。主要药代动力学参数为从 0 外推至无穷大的血清浓度-时间曲线下面积（AUC）。药代动力学参数采用方差分析的一般线性模型进行分析。次要终点包括安全性和耐受性。
结果
在纳入的 111 名受试者中，110 名受试者纳入药代动力学分析（Myl-1402O，n=37；欧盟参考贝伐珠单抗，n=36；美国参考贝伐珠单抗，n=37）。Myl-1402O 与欧盟参考贝伐珠单抗、Myl-1402O 与美国参考贝伐珠单抗以及欧盟参考贝伐珠单抗与美国参考贝伐珠单抗之间均显示出生物等效性，最小二乘均值比值的 AUC 接近 1，90%置信区间在等效范围内（0.80-1.25）。次要药代动力学参数（从 0 到最后可定量浓度的时间的 AUC[AUC]、血清峰浓度 [C]、C 时间、消除率常数和消除半衰期）也相似，AUC 和 C 的比值 90%置信区间在 80-125%范围内。所有三组治疗均出现治疗后不良事件，与贝伐珠单抗的临床数据一致。
结论
在健康男性志愿者中，Myl-1402O 具有良好的耐受性，其药代动力学和安全性特征与欧盟参考贝伐珠单抗和美国参考贝伐珠单抗相似。未出现新的重大安全性问题（ClinicalTrials.gov，NCT02469987；ClinicalTrialsRegister.eu EudraCT，2014-005621-12；2015 年 6 月 12 日）。
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