SAR342434 is a biosimilar of insulin lispro (Humalog® U-100). Batches of SAR342434 were compared with Humalog® batches of either EU or US origin in a panel of in vitro biological assays that included insulin binding to insulin receptor (IR) isoforms A (IR-A) and B (IR-B) and IR-A/IR-B autophosphorylation. A surface plasmon resonance biosensor-based assay was developed to characterize the kinetics of insulin binding to solubilized full-length IR-A or IR-B. Insulin-dependent metabolic activity assays included inhibition of lipolysis in in vitro differentiated human adipocytes, glucose uptake in L6-myocytes, and repression of glucose-6-phosphatase gene expression in human hepatocytes. Mitogenic activity assays included insulin binding to insulin-like growth factor-1 receptor (IGF1R), IGF1R autophosphorylation, and cell proliferation in MCF-7 cells. Weighted geometric means and their respective 95% confidence intervals (CI) were calculated for all 50% inhibitory or effective concentration values and kinetic binding constants for IR-A and IR-B. Statistical evaluation of the data demonstrated that the 90% CIs of the ratio of geometric means between SAR342434 and Humalog® EU or Humalog® US were within the predefined acceptance limits for each assay. Insulin lispro as SAR342434 solution demonstrated similarity to both US- and EU-approved Humalog® based on a side-by-side biological similarity assessment.

中文翻译：

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快速作用的赖脯胰岛素产品SAR342434以及美国和欧盟批准的Humalog®的体外代谢和有丝分裂反应的比较。

SAR342434是赖脯胰岛素（U-100）的生物仿制药。在一系列体外生物学分析中，将SAR342434批次与欧盟或美国来源的Humalog®批次进行了比较，其中包括胰岛素与胰岛素受体（IR）亚型A（IR-A）和B（IR-B）和IR- A / IR-B自磷酸化。开发了基于表面等离子体共振生物传感器的测定法，以表征胰岛素与溶解的全长IR-A或IR-B结合的动力学。胰岛素依赖性代谢活性测定包括抑制体外分化的人脂肪细胞中的脂解，L6-肌细胞中的葡萄糖摄取以及人肝细胞中的葡萄糖-6-磷酸酶基因表达的抑制。有丝分裂活性测定包括胰岛素与胰岛素样生长因子1受体（IGF1R）的结合，IGF1R自磷酸化以及MCF-7细胞的细胞增殖。对于IR-A和IR-B的所有50％抑制或有效浓度值和动力学结合常数，计算了加权几何平均值及其各自的95％置信区间（CI）。数据的统计评估表明，SAR342434与Humalog®EU或Humalog®US之间的几何平均值之比的90％CI在每种测定的预定接受极限内。基于并行生物学相似性评估，赖脯胰岛素作为SAR342434溶液证明与美国和欧盟批准的Humalog®相似。数据的统计评估表明，SAR342434与EU或Humalog®US之间的几何均数比的90％CIs在每种测定的预定义接受范围内。基于并行生物学相似性评估，赖脯胰岛素作为SAR342434溶液证明与美国和欧盟批准的Humalog®具有相似性。数据的统计评估表明，SAR342434与EU或Humalog®US之间的几何均数比的90％CIs在每种测定的预定义接受范围内。基于并行生物学相似性评估，赖脯胰岛素作为SAR342434溶液证明与美国和欧盟批准的Humalog®具有相似性。