Population pharmacokinetic/pharmacodynamic model of LY06006 in Chinese healthy subjects and postmenopausal osteoporotic women

Aims LY06006, a biosimilar of denosumab, is a recombinant fully human monoclonal antibody targeting the receptor activator of nuclear factor κB ligand. LY06006 has completed Phase I and Phase III clinical studies. The objective of this study is to develop a pharmacokinetic (PK)/pharmacodynamic (PD) model of LY06006 in healthy male and osteoporotic female populations in China. Methods In total, 420 subjects were enrolled in this study, including 84 healthy male subjects from the Phase I study and 336 osteoporotic postmenopausal women from the Phase III study. A nonlinear mixed‐effects model was used for model development. The free serum concentration of LY06006 was used for PK analysis, and Type 1 collagen C‐terminal telopeptide was used for PD analysis. Results A two‐compartment Michaelis–Menten approximate model was used to describe the PK profiles of LY06006. Body weight was a significant covariate for the volume of distribution of the central compartment (V 1 ) and clearance. The estimated values of V 1 in postmenopausal women with osteoporosis were 0.87×, those observed in healthy male subjects. The indirect effect model was used to describe PK/PD relationship. Subjects' height significantly influenced the baseline values of C‐terminal telopeptide. Conclusion A population PK/PD model was developed in Chinese healthy male subjects and postmenopausal osteoporotic women. A 60‐mg dose of LY06006 achieves similar PD efficacy to denosumab. Clinical trial registration: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ): ChiCTR2000039637, ChiCTR2000032882.