Drug Design, Development and Therapy (Mar 2019)
Physicochemical characterization and phase I study of CMAB008, an infliximab biosimilar produced by a different expression system
Abstract
Qing An,1,* Yingxin Zheng,2,3,* Yirong Zhao,2,* Tao Liu,2 Huaizu Guo,2 Dapeng Zhang,2–4 Weizhu Qian,5 Hao Wang,5 Yajun Guo,2,4,6,7 Sheng Hou,2,4 Jing Li2,81Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Jiangsu, China; 2State Key Laboratory of Antibody Medicine and Targeted Therapy; Shanghai, China; 3Obstetrics and Gynecology Hospital of Fudan University; Shanghai, China; 4School of Pharmacy, Liaocheng University, Liaocheng, China; 5Shanghai Key Laboratory of Cell Engineering, Shanghai, China; 6School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China; 7Institute of Molecular and Cell Biology, Proteos, Singapore; 8Shanghai Zhangjiang Biotechnology Co., Ltd; Shanghai, China*These authors contributed equally to this workBackground: 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.Methods: In this study, infliximab and CMAB008 were compared on physicochemical and biological characterizations, including protein content, activity, physiochemical integrity, impurities, additives, and immunogenicity.Results: 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.Conclusion: In summary, CMAB008 might have the potential to be an effective drug compared with infliximab. Keywords: infliximab, biosimilar, “biobetter”, CMAB008, immunogenicity
