Int J Clin Pharmacol Ther. 2022 Jun;60(6):269-279. doi: 10.5414/CP204176.
To compare the pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity between SB12 (a proposed eculizumab biosimilar) and the reference product (RP) eculizumab (i.e., European Union (EU)-sourced Soliris and United States (US)-sourced Soliris).
In this phase I study, healthy adult subjects were randomized to receive a 300-mg dose of SB12 or RP eculizumab via intravenous infusion. The PK endpoints were area under the serum concentration-time curve from time zero to infinity and to the last quantifiable concentration, and maximum serum concentration. Bioequivalence for the PK endpoints was determined if the 90% confidence intervals (CIs) for the ratio of geometric least squared means (Lsmeans) were within the pre-defined bioequivalence margins of 80.00 - 125.00%. PD, safety, and immunogenicity were also investigated.
The 90% CIs of the geometric Lsmeans ratios of the PK endpoints were fully contained within the pre-defined bioequivalence margin. PD profiles and incidence of treatment-emergent adverse events across treatment groups were comparable. Incidence of anti-drug antibodies was also comparable between all groups, and a positive result for neutralizing antibodies was not detected.
This study demonstrated PK bioequivalence and similar PD, safety, and immunogenicity profiles of SB12 to both reference eculizumab products.
比较 SB12（一种拟议的依库珠单抗生物类似药）与参照产品（即欧盟来源的 Soliris 和美国来源的 Soliris）的药代动力学（PK）、药效学（PD）、安全性和免疫原性。
在这项 I 期研究中，健康成年受试者被随机分配接受 300mg 剂量的 SB12 或 RP 依库珠单抗静脉输注。PK 终点为从零时到无穷大的血清浓度-时间曲线下面积和到最后可定量浓度的最大血清浓度。如果几何最小二乘均值（Lsmeans）比值的 90%置信区间（CI）在 80.00-125.00%的预设生物等效性范围内，则认为 PK 终点具有生物等效性。还研究了 PD、安全性和免疫原性。
PK 终点的几何 Lsmeans 比值的 90%CI 完全包含在预设的生物等效性范围内。治疗组的 PD 谱和治疗后出现的不良事件发生率相似。各组的抗药物抗体发生率也相似，未检测到中和抗体的阳性结果。
这项研究表明 SB12 与参照依库珠单抗产品具有 PK 生物等效性和相似的 PD、安全性和免疫原性特征。
