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

Abstract

Objective

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.

Methods

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.

Results

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–∞ 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.

Conclusions

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.

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