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Pharmacokinetics, Tolerability, Safety, and Immunogenicity of LY01008 and Bevacizumab (Avastin®) in Healthy Chinese Subjects

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Background and Objective

LY01008 had been identified as being highly similar to the bevacizumab reference product in the pharmacy and pharmacology terms. The primary objective of this study was to compare the pharmacokinetic characteristics of the biosimilar candidate LY01008 with that of the bevacizumab (Avastin®) reference product after a single intravenous infusion in healthy Chinese adults. The secondary objective was to compare the safety and immunogenicity of LY01008 with those of bevacizumab.

Methods

In this double-blind, parallel-group, phase I study, 102 male subjects aged 18–45 years were randomized 1:1 to receive a single intravenous infusion of 3 mg/kg LY01008 or bevacizumab. Before the pivotal section, 12 healthy male subjects receiving a single intravenous (IV) infusion of 0.5 mg/kg or 1.5 mg/kg LY01008 were screened to verify the safety and tolerability of LY01008. Primary endpoints included the area under the concentration–time curve (AUC) from time zero to the last quantifiable time point (AUC0–t), AUC from time zero to the infinity time (AUC0–inf), and maximum plasma concentration (Cmax).

Results

The geometric mean ratios (GMRs) (90% confidence intervals, CIs) of AUC0–t, AUC0–inf, and Cmax of LY01008 to bevacizumab were 87.62% (82.91%, 92.61%), 87.27% (82.46%, 92.35%), and 96.45% (91.37%, 101.81%), respectively, in the pivotal section, which were within the prespecified equivalence margin of 80.00–125.00%. LY01008 and bevacizumab administered as a single 3 mg/kg intravenous dose were comparably well tolerated. No new or unexpected adverse events were observed. Nine subjects had antidrug antibodies (ADAs) (5 in the LY01008 group and 4 in the bevacizumab group) after dosing. No neutralizing antibody (Nab) was detected.

Conclusion

LY01008, a recombinant humanized monoclonal antibody (mAb) against vascular endothelial growth factor (VEGF), displayed pharmacokinetic similarity to bevacizumab, and good safety and tolerability profiles. The data from this trial provide fundamental information for further development.

Trial Registration

Clinical trial registration ID: CTR20170191.

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Acknowledgements

The authors thank all the subjects and their families who participated in the studies.

Author information

Author notes

  1. Lijun Xie, Ying Zhu have contributed equally to this paper.

Authors and Affiliations

  1. Phase I Clinical Trial Unit, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China

    Lijun Xie, Ying Zhu, Zuojun Liang, Yuqing Zhao, Sufeng Zhou, Juan Chen, Hongwen Zhang, Sijia Ding, Lu Wang & Feng Shao

  2. Department of Clinical Pharmacology, School of Pharmacy College, Nanjing Medical University, Nanjing, 211166, Jiangsu, China

    Ying Zhu & Feng Shao

Authors
  1. Lijun Xie
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  2. Ying Zhu
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  9. Lu Wang
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  10. Feng Shao
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Corresponding authors

Correspondence to Lu Wang or Feng Shao.

Ethics declarations

Funding

This study was funded by Boan Biotech Co., Ltd., Yantai city, Shandong province, China.

Availability of data and material

The data generated during this study are available from the corresponding author for reasonable requests.

Code availability

Not applicable.

Conflicts of interest

The authors have indicated that there are no conflicts of interest associated with the content of this article.

Ethical approval

The study protocols were conducted in accordance with the declaration of the ethical standards of the institutional and/or national research committee and with the Declaration of Helsinki. The studies were approved by the Ethics Committee of the First Affiliated Hospital with Nanjing Medical University (Nanjing, China).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Author contributions

(I) Conception and design: FS. (II) Administrative support and provision of study materials or subjects: LX, ZL, SZ, JC, HZ, SD. (III) Collection and assembly of data: LX, JC. (IV) Data analysis and interpretation: FS, LW. (V) Manuscript writing: LX, YZ, FS, LW. (VI) Final approval of manuscript: all authors.

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Not applicable.

Additional information

The authors confirm that the PI for this paper is Feng Shao and the co-investigator is Lu Wang. They had direct clinical responsibility for subjects

Supplementary Information

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Xie, L., Zhu, Y., Liang, Z. et al. Pharmacokinetics, Tolerability, Safety, and Immunogenicity of LY01008 and Bevacizumab (Avastin®) in Healthy Chinese Subjects. Eur J Drug Metab Pharmacokinet 47, 309–317 (2022). https://doi.org/10.1007/s13318-021-00752-7

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  • DOI: https://doi.org/10.1007/s13318-021-00752-7

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