Safety and pharmacokinetics of a biosimilar of denosumab (KN012): Phase 1 and bioequivalence study in healthy Chinese subjects

ABSTRACT

Background

KN012 is a proposed biosimilar candidate for the reference drug denosumab, with the brand name Prolia®. This study explored the tolerance, variability, and pharmacokinetics (PK) of denosumab and its biosimilar in healthy Chinese subjects.

Research design and methods

A randomized, double-blind, parallel, two-arm study was performed to analyze the bioequivalence of denosumab biosimilar (60 mg) compared with denosumab.

Results

The PK properties of denosumab biosimilar were similar to those of denosumab. When denosumab biosimilar was compared to denosumab, the geometric mean ratios (GMRs) of C_max, AUC_0-t, and AUC_0-∞ were 98.74%, 102.54%, and 102.18%, respectively, and the 90% confidence interval was observed to be within 80–125%. The inter-subject variability ranged from 31.4% to 34.6%. Five subjects in the denosumab biosimilar group and one subject in the denosumab group were positive for anti-drug antibodies (ADAs) and negative for neutralizing antibodies (NAbs). Adverse reactions were observed in 100% (52 subjects) and 94.0% (47 subjects) of the subjects in the denosumab biosimilar and denosumab groups, respectively. Reductions in the blood calcium and phosphate levels were the most common adverse reactions.

Conclusion

The PK characteristics were comparable for the denosumab biosimilar and denosumab groups. Their safety profiles were also similar.

Trial Registration

: The trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html #CTR20181231).

KEYWORDS:

• Inter-subject variability
• pharmacokinetics
• biosimilar
• immunogenicity
• denosumab

Author contributions

Hong Zhang, Cuiyun Li, Jingrui Liu, Boguang Wang, Yanhong Mao, Yanhua Ding, and Qinglong Jin designed the experiment. Hong Zhang, Cuiyun Li, Jingrui Liu, Min Wu, Xiaojiao Li, Xiaoxue Zhu and Qianqian Li performed the clinical trials. Hong Zhang, Cuiyun Li, and Yanhua Ding analyzed the data and wrote the paper. Hong Zhang and Yanhua Ding edited the paper and drew the figures.

Data availability statement:

The data that support the findings of this study are available from the corresponding author, Y.D., upon reasonable request.

Declaration of interest

All data related to this study were interpreted by the trial staff with complete independence from the sponsor. Boguang Wang and Yanhong Mao are employees of the sponsor team. 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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Feiyang Biotechnology (Jilin) Co. Ltd., China.