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.

Abstract

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. 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. 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. 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.