ABSTRACT

Background

Bevacizumab (BEV) is a recombinant humanized monoclonal immunoglobulin G1 antibody that binds to vascular endothelial growth factor (VEGF)-A and acts as an antiangiogenic agent. It is approved for treatment of many cancer indications, including metastatic colorectal cancer and nonsquamous non–small cell lung cancer.

Research Design and Methods

The analytical similarity of the BEV biosimilar MYL-1402O to reference BEV sourced from the European Union and United States was assessed using physicochemical and functional tests to support the clinical development of MYL-1402O. Assessment of physicochemical and analytical similarity showed that MYL-1402O has the same amino acid sequence and similar posttranslational modification profile as the reference BEV products.

Results

The functional and biologic activity of MYL-1402O assessed using inhibition of VEGF-induced cell proliferation in human umbilical vein endothelial cells, inhibition of VEGF-induced VEGF receptor 2 phosphorylation, and fragment antigen and fragment crystallizable receptor binding, was comparable to reference BEV products.

Conclusions

The totality of the data assessment confirms the high degree of similarity of MYL-1402O to reference BEV with respect to physicochemical and in vitro functional properties. The product quality data presented here, along with data from phase 1 clinical studies, demonstrate the similarity of MYL-1402O to reference BEV products, supporting further clinical development of this BEV biosimilar.

中文翻译：

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MYL-1402O 与参考贝伐单抗的分析相似性评估

摘要

背景

贝伐单抗 (BEV) 是一种重组人源化单克隆免疫球蛋白 G1 抗体，可与血管内皮生长因子 (VEGF)-A 结合并作为抗血管生成剂。它被批准用于治疗许多癌症适应症，包括转移性结直肠癌和非鳞状非小细胞肺癌。

研究设计和方法

使用物理化学和功能测试评估了生物仿制药 BEV MYL-1402O 与来自欧盟和美国的参考 BEV 的分析相似性，以支持 MYL-1402O 的临床开发。理化和分析相似性评估表明，MYL-1402O 具有与参考 BEV 产品相同的氨基酸序列和相似的翻译后修饰谱。

结果

MYL-1402O 的功能和生物活性通过抑制人脐静脉内皮细胞中的 VEGF 细胞增殖、抑制 VEGF 诱导的 VEGF 受体 2 磷酸化以及片段抗原和片段可结晶受体结合来评估，与参考 BEV 产品相当.

结论

数据评估的整体证实了 MYL-1402O 在物理化学和体外功能特性方面与参考 BEV 的高度相似性。此处提供的产品质量数据以及来自 1 期临床研究的数据证明了 MYL-1402O 与参考 BEV 产品的相似性，支持这种生物仿制药 BEV 的进一步临床开发。