Pharmacokinetic similarity study comparing the biosimilar candidate, LY05008, with its reference product dulaglutide in healthy Chinese male subjects

ABSTRACT

Background

Dulaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been approved for improving glycemic control and reducing the risk of cardiovascular (CV) adverse events. This study compared the pharmacokinetic (PK) profiles, safety, and immunogenicity of LY05008, a biosimilar candidate, to a licensed product dulaglutide in healthy Chinese male subjects.

Research design and methods

In this double-blind, open-label, parallel-group study, healthy Chinese male subjects were randomized 1:1 to receive either LY05008 or dulaglutide subcutaneously. Primary study endpoints were PK parameters such as the area under the concentration-time curve (AUC) from time zero to infinity (AUC_{0 – ∞}), AUC from time zero to the last quantifiable concentration (AUC_0–t), and maximum serum concentration (C_max). Safety and immunogenicity profiles were also included for data analysis.

Results

82 subjects were randomized to receive LY05008 (n = 41) or dulaglutide (n = 41). The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUC_{0 – ∞,} AUC_0–t and C_max of LY05008 to dulaglutide were all within the bioequivalence limits of 80%-125%. Other PK parameters, safety, and immunogenicity profiles were comparable across the two treatment groups.

Conclusion

This study demonstrated PK similarity of LY05008, a dulaglutide biosimilar, to dulaglutide in healthy Chinese male subjects, with comparable safety and immunogenicity data.

Trial registration

The trial is registered at the Chinese Clinical Trial Registry (Identifier No. ChiCTR2200066519).

KEYWORDS:

• Dulaglutide
• biosimilar
• pharmacokinetic similarity
• safety
• immunogenicity
• bioequivalence

Acknowledgments

We thank the participants for involving in this trial. We acknowledge the contribution of Ximaidi Biological Technology Co., Ltd. (Nanjing, China) for formulating a statistical analysis plan.

Declaration of interests

C Dou is an employee of Shandong Boan Biotechnology Co., Ltd., Yantai, China. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed involvement in speakers’ bureaus for Novo Nordisk. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Ethics statement

This study was reviewed and approved by the Institutional Review Board of the Second Hospital of Anhui Medical University. Written informed consent was obtained from all subjects prior to enrollment in the study.

Author contributions

W Hu was the leading principal investigator of this study, contributed to study conception, study design, data analysis and interpretation, manuscript drafting, and editing. Q Zhang, C Sun, J Wu, RP Zhou, and W Hu were involved in patient recruitment and data acquisition. J Wu and X Zhang did the literature search, research data analysis, and interpretation, and drafted the manuscript. YY Liu, C Dou, H Qian and Q Zhang were involved in the literature search, data acquisition, analysis, and interpretation. All authors contributed to development of the manuscript and approved the final version for submission.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14712598.2023.2189009

Additional information

Funding

This paper was funded by the National Major Scientific and Technological Special Project (Grant No. 2020ZX09201014) and Shandong Boan Biotechnology Co., Ltd., Yantai, China.