Tolerance, variability, and pharmacokinetics of bevacizumab biosimilars in Chinese healthy male subjects

作者：Zhang, Hong; Li, Qingmei; Zhu, Xiaoxue; Li, Cuiyun; Li, Xiaojiao; Liu, Chengjiao; Hu, Yue; Chen, Guiling; Wei, Haijing; Wang, Jing; Shen, Zhenwei; Ding, Yanhua^*

来源：Cancer Chemotherapy and Pharmacology, 2018, 82(4): 615-623.

DOI：10.1007/s00280-018-3645-1

• Bevacizumab
• Biosimilar
• Immunogenicity
• Pharmacokinetics
• Inter-subject variability

The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of bevacizumab biosimilars (MIL60, BAT1706, IBI305) in Chinese healthy male subjects. @@@ This randomized, double-blind, two-arm, parallel studies included three separate investigations, which were conducted by three sponsors to investigate the bioequivalence of bevacizumab biosimilars (MIL60, BAT1706, IBI305) with that of bevacizumab-EU as a reference drug. Subjects received a single-dose of 1 or 3 mg/kg of the bevacizumab biosimilars or bevacizumab-EU and were followed up for 70-99 days. Serum concentrations of bevacizumab, antidrug antibody (ADA), and neutralizing antibody (NAb) were measured using electrochemiluminescence. In addition, the PK parameters were determined using non-compartmental methods. The safety assessments included adverse events, hematology tests, and biochemistry tests. @@@ The three bevacizumab biosimilars exhibited similar PK properties to that of bevacizumab-EU. Bevacizumab demonstrated linear PK properties and a concentration-dependent disposition. When comparing the three biosimilars with bevacizumab-EU, the 90% CIs of the ratios for C (max), AUC(0-t) , and AUC(0-a) were within 80-125%. The inter-CV ranged from 12.6 to 23.3%. Three subjects in the biosimilar groups and bevacizumab-EU were positive for the ADA and negative for the NAb. Treatment-related mild or moderate adverse events were reported in 56-80 and 36-80% of subjects in the biosimilar and bevacizumab treatment arms, respectively. @@@ The bevacizumab biosimilars exhibit similar PK characteristics to that of the reference product bevacizumab-EU. The inter-CV is moderate and less than 25% in all cases. The safety profile was similar among bevacizumab biosimilars and bevacizumab-EU with significant adverse events.

• 出版日期2018-10
• 单位吉林大学