A three-arm clinical study to compare pharmacokinetic and pharmacodynamic similarity of the denosumab biosimilar LY06006 with reference denosumab in healthy male subjects.

Background: This study aimed to evaluate the pharmacokinetic (PK), pharmacodynamic (PD) similarity, comparable safety, and immunogenicity between LY06006, European Union-sourced denosumab (EU-DEN), and United States-sourced denosumab (US-DEN).

Research design and methods: In this double-blind, parallel-group, and single-dose study, 300 healthy male subjects were randomized 1:1:1 to receive a 60 mg dose of either LY06006, EU-DEN, or US-DEN subcutaneously. This study lasted for 253 days. Primary PK endpoints included maximum serum concentration (C_max), area under the concentration-time curve (AUC) from time zero to last quantifiable concentration (AUC_0-t), and AUC from time zero to infinity (AUC_0-inf). Pharmacokinetic equivalence was concluded if the two-sided 90% confidence interval (CI) for the geometric least squares mean ratio (GLSMR) of primary endpoints were within 80%-125%. Other PK parameters, PD parameters, safety, and immunogenicity assessments were also conducted during the study.

Results: The 90% CIs for ratios of GLSMR were within the predefined equivalence margin for AUC_0-inf (89.0%-111.1%), AUC_0-t (89.7%-111.3%), and C_max (92.3%-106.7%). The PD parameters, safety, and immunogenicity of LY06006 were also comparable to US-DEN and EU-DEN.

Conclusion: LY06006 was highly similar to US-DEN and EU-DEN in terms of PK, PD, safety and immunogenicity in healthy male subjects.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT06095427.