Journal of Orthopaedic Translation (Jan 2023)

Denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women: A randomized, double-blind, placebo-controlled, multicenter phase III study

  • Jiemei Gu,
  • Hao Zhang,
  • Qingyun Xue,
  • Li Wang,
  • Zhifeng Cheng,
  • Yawei Zhang,
  • Qifu Li,
  • Lingqing Yuan,
  • Yukun Li,
  • Jin Dong,
  • Yanan Huo,
  • Xin Tang,
  • Ling Hu,
  • Xinjia Wang,
  • Fei Hua,
  • Lin Shen,
  • Jinluo Cheng,
  • Huimin Zhou,
  • Youjia Xu,
  • Tao Yang,
  • Chuansuo Wang,
  • Jin Xu,
  • Jie Shen,
  • Ying Zhang,
  • Xiaomei Zhang,
  • Dun Hong,
  • Xiaoling Guan,
  • Xinhua Xiao,
  • Guang Wang,
  • Yonghua Liu,
  • Liujun Fu,
  • Jianting Chen,
  • Xigao Cheng,
  • Yue Ding,
  • Lijun Liu,
  • Qi Yao,
  • Xinchao Zhang,
  • Lixin Li,
  • Panjun Zhang,
  • Chunying Deng,
  • Chengyan Jiang,
  • Li You,
  • Kai Wang,
  • Shimin Zhang,
  • Jianzhong Xiao,
  • Wei Liu,
  • Xiaohong Du,
  • Xianwen Shang,
  • Tianrong Pan,
  • Chen Lei,
  • Shuren Guo,
  • Zhenlin Zhang

Journal volume & issue
Vol. 38
pp. 117 – 125

Abstract

Read online

Objectives: This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50–85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60 ​mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint. Results: Of the 448 randomized patients, 409 (LY06006, n ​= ​311; placebo, n ​= ​98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P ​< ​0.0001). For the secondary endpoints, LY06006 was associated with increased lumbar spine BMD levels measured at month 6, BMD levels at the femoral neck, total hip, and trochanter measured at months 6 and 12 and reduced serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 ​N-peptide (P1NP) levels at months 1, 6, and 12. Safety analysis was based on the safety analysis set (SS), and 264 (78.6%) subjects in the LY06006 group and 83 (75.5%) in the placebo group experienced adverse events (AEs). Most events were mild or moderate and not related to the study drugs. Conclusion: In postmenopausal women with a high risk of fracture, LY06006 increased the BMD and decreased bone resorption; thus, LY06006 might be an effective treatment for osteoporosis. LY06006 was generally safe and well tolerated without unexpected adverse reactions, similar to the reference drug Prolia®. The characteristics of effectiveness and safety were similar to those reported in previous studies. The translational potential of this article: In this multi-center, randomized, double-blind, placebo-controlled phase 3 study, LY06006 showed substantially efficacy to increase BMD and well tolerance without unexpected adverse reactions, which is comparable to the reference drug Prolia ®. The presented results are encouraging and can offer some valuable evidence for the clinical practice.

Keywords