Comparison of KN012, a denosumab biosimilar, versus reference denosumab in Chinese postmenopausal women with osteoporosis: efficacy, safety, and population pharmacokinetics in a 12-month phase III study.

Purpose: To evaluate the efficacy, safety, bone turnover markers, population pharmacokinetics, and immunogenicity profiles of KN012 compared to US reference denosumab (US-denosumab) in Chinese postmenopausal osteoporotic patients. Methods: This 12-month, double-blind, randomized, active-controlled Phase III study enrolled 279 participants who were randomized in a 1:1 ratio to receive either 60 mg of KN012 or US-denosumab subcutaneously at months 0 and 6. The primary endpoint was the mean percent change in lumbar spine bone mineral density (BMD) from baseline at Month 12. Efficacy equivalence was concluded if the associated 95% confidence intervals (CI) for least squares (LS) mean group differences fell within ±1.75%. The Secondary endpoints included percent changes in BMD at the hip, femoral neck, and trochanter. Safety, bone turnover markers, population pharmacokinetics, and immunogenicity were assessed throughout the study period. Results: The primary efficacy analysis indicated that the LS mean difference between the KN012 group and the US-denosumab group was 0.22% (95% CI, -0.78, 1.23) in the full analysis set (FAS) and 0.11% (95% CI,-0.92, 1.14) in the per-protocol set (PPS). Both confidence intervals fell entirely within the predefined equivalence margin (±1.75%), confirming clinical equivalence between KN012 and US-denosumab. Secondary efficacy endpoints, safety, bone turnover markers, population pharmacokinetics, and immunogenicity results were comparable between the two groups up to Month 12. Conclusions: KN012 demonstrates comparable efficacy, safety, bone turnover markers, population pharmacokinetics, and immunogenicity to US-denosumab in Chinese postmenopausal women with osteoporosis at high risk of fracture.