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

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:

• infliximab
• biosimilar
• “biobetter”
• CMAB008
• immunogenicity

Acknowledgments

This work was supported by grants from the Ministry of Science and Technology of China (863 projects 2014AA021004), Shanghai Rising-Star Program (16QB1404300), and Shanghai Key Technologies R&D Program of Biological Medicine (15431906100, 16431901200, 16431904700, 16431904100, and 16DZ1910400).

Author contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Supplementary materials

Figure S1 Comparison of CMAB008 and infliximab at intact mass-spectrometry level after peptide-N-glycosidase F treatment.

Figure S2 Comparison of the heavy chain of CMAB008 and Infliximab after carboxypeptidase B treatment by liquid-chromatography mass-spectrometry analysis.

Table S1 AE profiles of CMAB008 and Remicade