An Qing, Zheng Yingxin, Zhao Yirong, Liu Tao, Guo Huaizu, Zhang Dapeng, Qian Weizhu, Wang Hao, Guo Yajun, Hou Sheng, Li Jing
Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Jiangsu, China.
State Key Laboratory of Antibody Medicine and Targeted Therapy; Shanghai, China,
Drug Des Devel Ther. 2019 Mar 12;13:791-805. doi: 10.2147/DDDT.S170913. eCollection 2019.
Infliximab (Remicade), a chimeric monoclonal antibody against human TNFα, will inevitably face competition from biosimilar products, because of its effectiveness in autoimmune diseases and rapidly increasing market demand. According to guidelines for biosimilar development, the "biosimilar-expression system" may differ from that of the innovator, but more appropriate studies should be carried out to demonstrate the comparability between biosimilar and innovator. CMAB008 is an infliximab biosimilar candidate developed by the State Key Laboratory of Antibody Medicine and Targeted Therapy of China. Infliximab was expressed in SP2/0 cells, while CMAB008 was produced in a CHO-expression system.
In this study, infliximab and CMAB008 were compared on physicochemical and biological characterizations, including protein content, activity, physiochemical integrity, impurities, additives, and immunogenicity.
The results showed that they were highly similar and comparable, except some differences in glycosylation. As glycosylation profiles can influence immunogenicity and occurrence of allergy or other adverse reactions of antibody therapeutics, primary tolerability and pharmacokinetics of CMAB008 were evaluated. In the phase I clinical trial, plasma concentration of CMAB008 and antidrug antibodies were also measured using ELISA and bridging ELISA, respectively. CMAB008 exhibited favorable clinical tolerability, no adverse events in the 3 mg/kg single-dose group (recommended therapeutic dosage), and no serious adverse events in the multiple-dose group. Also, no injection-site reactions were observed in the experiment.
In summary, CMAB008 might have the potential to be an effective drug compared with infliximab.
英夫利昔单抗（类克）是一种抗人肿瘤坏死因子α的嵌合单克隆抗体，因其在自身免疫性疾病中的有效性以及市场需求的迅速增长，不可避免地将面临生物类似药产品的竞争。根据生物类似药研发指南，“生物类似药表达系统”可能与创新药不同，但应开展更恰当研究以证明生物类似药与创新药之间的可比性。CMAB008是中国抗体药物与靶向治疗国家重点实验室研发的一种英夫利昔单抗生物类似药候选产品。英夫利昔单抗在SP2/0细胞中表达，而CMAB008在CHO表达系统中生产。
在本研究中，对英夫利昔单抗和CMAB008进行了理化和生物学特性比较，包括蛋白质含量、活性、理化完整性、杂质、添加剂和免疫原性。
结果显示，除了糖基化存在一些差异外，它们高度相似且具有可比性。由于糖基化谱可影响抗体治疗药物的免疫原性以及过敏或其他不良反应的发生，因此对CMAB008的初步耐受性和药代动力学进行了评估。在I期临床试验中，还分别使用酶联免疫吸附测定（ELISA）和桥接ELISA检测了CMAB008的血浆浓度和抗药抗体。CMAB008表现出良好的临床耐受性，3mg/kg单剂量组（推荐治疗剂量）未出现不良事件，多剂量组也未出现严重不良事件。此外，实验中未观察到注射部位反应。
总之，与英夫利昔单抗相比，CMAB008可能有潜力成为一种有效的药物。
