Amgen Inc., Thousand Oaks, CA, USA.
Eur J Haematol. 2020 Jul;105(1):66-74. doi: 10.1111/ejh.13411. Epub 2020 Apr 27.
ABP 959 is a proposed biosimilar to eculizumab, a monoclonal antibody targeting the human C5 complement protein. The objective of this randomized, double-blind, three-arm, study was to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) similarity of ABP 959 relative to the eculizumab reference product (RP) in healthy adult male subjects.
Eligible subjects aged 18-45 years were randomized to receive a 300-mg IV infusion of ABP 959, or FDA-licensed eculizumab (eculizumab US), or EU-authorized eculizumab (eculizumab EU). Primary PK endpoint was area under the total serum concentration-time curve from 0 to infinity (AUC ); primary PD endpoint was area between the effect curve (ABEC) of CH50-time data.
The geometric mean of PK and PD parameters were similar between ABP 959 versus eculizumab US and eculizumab EU; PK and PD similarity was established based on 90% confidence intervals of the geometric mean ratio being within prespecified equivalence margin of 0.8 and 1.25. The incidence of treatment-emergent adverse events was similar across groups. The incidence of binding anti-drug antibodies was similar across treatments; no subjects developed neutralizing antibodies.
This study demonstrated PK and PD similarity of ABP 959 to eculizumab RP; safety and immunogenicity profiles were also similar.
ABP959 是一种针对人 C5 补体蛋白的单克隆抗体依库珠单抗的拟生物制剂。这项随机、双盲、三臂研究的目的是证明 ABP959 在健康成年男性受试者中的药代动力学（PK）和药效学（PD）与依库珠单抗参比制剂（RP）相似。
年龄在 18-45 岁之间的合格受试者被随机分配接受 300 毫克静脉注射 ABP959、或美国食品和药物管理局批准的依库珠单抗（依库珠单抗美国）、或欧盟授权的依库珠单抗（依库珠单抗欧盟）。主要 PK 终点是血清总浓度-时间曲线下面积从 0 到无穷大（AUC）；主要 PD 终点是 CH50-时间数据的效应曲线下面积（ABEC）。
ABP959 与依库珠单抗美国和依库珠单抗欧盟的 PK 和 PD 参数的几何平均值相似；基于 90%置信区间的几何均数比值在预设的 0.8 和 1.25 等效区间内，确定了 PK 和 PD 相似性。各组治疗后出现不良事件的发生率相似。各组治疗中出现结合性抗药物抗体的发生率相似；没有受试者产生中和抗体。
这项研究表明 ABP959 与依库珠单抗 RP 的 PK 和 PD 相似；安全性和免疫原性特征也相似。
