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Drug Des Devel Ther. 2019 Mar 12;13:791-805. doi: 10.2147/DDDT.S170913. eCollection 2019.

Physicochemical characterization and phase I study of CMAB008, an infliximab biosimilar produced by a different expression system.

An Q1, Zheng Y2,3, Zhao Y2, Liu T2, Guo H2, Zhang D2,3,4, Qian W5, Wang H5, Guo Y2,4,6,7, Hou S2,4, Li J2,8.

Author information

1
Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Jiangsu, China.
2
State Key Laboratory of Antibody Medicine and Targeted Therapy; Shanghai, China, housheng301@163.com; lijing8523@163.com.
3
Obstetrics and Gynecology Hospital of Fudan University; Shanghai, China.
4
School of Pharmacy, Liaocheng University, Liaocheng, China, housheng301@163.com.
5
Shanghai Key Laboratory of Cell Engineering, Shanghai, China.
6
School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
7
Institute of Molecular and Cell Biology, Proteos, Singapore.
8
Shanghai Zhangjiang Biotechnology Co., Ltd; Shanghai, China, lijing8523@163.com.

Abstract

Background:

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:

CMAB008; biosimilar; immunogenicity; infliximab; “biobetter”

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