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

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 Cmax, AUC0-t, and AUC0-∞ 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).