Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of a biosimilar of denosumab (LY06006): a randomized, double-blind, single-dose, parallel-controlled clinical study in healthy Chinese subjects

ABSTRACT

Objectives

To compare the pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity of LY06006 (denosumab biosimilar) and denosumab in healthy Chinese adult male subjects.

Methods

In this randomized, double-blind, parallel-controlled, single-dose, comparative biosimilar study, a total of 168 subjects received 60 mg of LY06006 or denosumab by subcutaneous (SC) abdominal injections in a 1:1 ratio with a follow-up period of 168 days.

Results

After a single SC abdominal injection of 60 mg LY06006/denosumab, the geometric mean ratio of the main pharmacokinetic parameters, C_max and AUC_0-∞, of the two drugs were 97.57% and 104.27%, respectively; the geometric mean ratio of the main pharmacodynamic parameters AUEC_0-t and E_max, were 101.00% and 99.64%, respectively, and the 90% confidence interval was observed to be within 80–125%. The subjects in the test group (LY06006) and control group (denosumab) were all negative for anti-drug antibody (ADA). The incidence and severity of treatment-emergent adverse events (TEAEs)were similar for both groups, and no grade 3 or higher TEAEs occurred in either group.

Conclusions

This study demonstrated that LY06006 and denosumab have similar characteristics and bioequivalence in pharmacokinetics. Moreover, they had similar pharmacodynamic profiles, safety, and immunogenicity.

Clinical trial registration

www.clinicaltrials.gov identifier is NCT04973722

KEYWORDS:

• Denosumab
• biosimilar
• pharmacokinetics
• pharmacodynamics
• immunogenicity

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have received an honorarium from Expert Opinion on Investigational Drugs for their review work. One reviewer has declared research grants from Pfizer, Abbvie and Bristol Myers Squibb. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

Yuxia Xiang, Guoping Yang designed the experiment. Siyi Wang, Xiaoyan Yang, Jie Huang, Shuang Yang, Qian Wu, Honghui Chen, Shuting Wu performed the clinical trials. Jie Huang, Qian Wu, Honghui Chen, Shuting Wu analyzed the data. Siyi Wang, Xiaoyan Yang, Changlin Dou wrote the paper and edited the paper.

Additional information

Funding

This work was supported by the [National Natural Science Foundation of China]; under Grant [number 81803639]; [Hunan Provincial Natural Science Foundation of China] under Grant [number 2020JJ5852]; and [The Key Research and Development Project of Hunan Province] under Grant [number 2020SK2010].