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

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

作者地址:"[Gu, Jiemei; Zhang, Hao; Zhang, Zhenlin] Shanghai Jiao Tong Univ, Shanghai Clin Res Ctr Bone Dis, Dept Osteoporosis & Bone Dis, Peoples Hosp 6, Shanghai 200233, Peoples R China; [Xue, Qingyun] Beijing Hosp, Beijing, Peoples R China; [Wang, Li] Tianjin Hosp, Tianjin, Peoples R China; [Cheng, Zhifeng] Harbin Med Univ, Affiliated Hosp 4, Harbin, Peoples R China; [Zhang, Yawei] Jiangxi Pingxiang Peoples Hosp, Pingxiang, Peoples R China; [Li, Qifu] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China; [Yuan, Lingqing] Cent South Univ, Xiang ya Hosp 2, Changsha, Peoples R China; [Li, Yukun] Third Hosp Hebei Med Univ, Shijiazhuang, Peoples R China; [Dong, Jin] Shanxi Med Univ, Hosp 1, Jinzhong, Peoples R China; [Huo, Yanan] Jiangxi Prov Peoples Hosp, Nanchang, Peoples R China; [Tang, Xin] Sichuan Univ, West China Sch Med, West China Hosp, Chengdu, Peoples R China; [Hu, Ling] First Hosp Nanchang, Nanchang, Peoples R China; [Wang, Xinjia] Shantou Univ Med Coll, Affiliated Hosp 2, Shantou, Peoples R China; [Hua, Fei] First Peoples Hosp Changzhou, Changzhou, Peoples R China; [Shen, Lin] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Huazhong, Peoples R China; [Cheng, Jinluo] Changzhou No 2 Peoples Hosp, Changzhou, Peoples R China; [Zhou, Huimin] Hebei Med Univ, Hosp 1, Shijiazhuang, Peoples R China; [Xu, Youjia] Soochow Univ, Affiliated Hosp 2, Suzhou, Peoples R China; [Yang, Tao] Chongqing Univ, Three Gorges Hosp, Chongqing, Peoples R China; [Wang, Chuansuo] Hainan Med Coll, Affiliated Hosp 1, Haikou, Peoples R China; [Xu, Jin] Shandong Prov Hosp, Jinan, Peoples R China; [Shen, Jie] Southern Med Univ, Shunde Hosp, Guangzhou, Peoples R China; [Zhang, Ying] Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou, Peoples R China; [Zhang, Xiaomei] Bengbu Med Coll, Affiliated Hosp 1, Bengbu, Peoples R China; [Hong, Dun] Taizhou Hosp Zhejiang Prov, Taizhou, Peoples R China; [Guan, Xiaoling] Shandong Prov Qianfoshan Hosp, Jinan, Peoples R China; [Xiao, Xinhua] Univ South China, Affiliated Hosp 1, Hengyang, Peoples R China; [Wang, Guang] Capital Med Univ, Affiliated Beijing Chao Yang Hosp, Beijing, Peoples R China; [Liu, Yonghua] Third Hosp Nanchang, Nanchang, Peoples R China; [Fu, Liujun] Henan Univ Sci & Technol, Affiliated Hosp 1, Luoyang, Peoples R China; [Chen, Jianting] Southern Med Univ, Nanfang Hosp, Guangzhou, Peoples R China; [Cheng, Xigao] Nanchang Univ, Affiliated Hosp 2, Nanchang, Peoples R China; [Ding, Yue] Sun Yat sen Univ, Sun Yat sen Mem Hosp, Guangzhou, Peoples R China; [Liu, Lijun] Yiyang Cent Hosp, Yiyang, Peoples R China; [Yao, Qi] Ningbo First Hosp, Ningbo, Peoples R China; [Zhang, Xinchao] Fudan Univ, Jinshan Hosp, Shanghai, Peoples R China; [Li, Lixin] Xiamen Hosp TCM, Xiamen, Peoples R China; [Zhang, Panjun] Yixing Peoples Hosp, Wuxi, Peoples R China; [Deng, Chunying] Zigong Fourth Peoples Hosp, Sichuan, Peoples R China; [Jiang, Chengyan] First Peoples Hosp Zunyi, Zunyi, Peoples R China; [Wang, Kai] Taizhou Hosp TCM, Taizhou, Peoples R China; [You, Li] Shanghai Gen Hosp, Shanghai, Peoples R China; [Zhang, Shimin] Tongji Univ, Yangpu Hosp, Shanghai, Peoples R China; [Xiao, Jianzhong] Beijing Tsinghua Changgung Hosp, Beijing, Peoples R China; [Liu, Wei] Nantong First Peoples Hosp, Nantong, Peoples R China; [Du, Xiaohong] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Peoples R China; [Shang, Xianwen] Guizhou Med Univ, Affiliated Hosp, Guiyang, Peoples R China; [Pan, Tianrong] Anhui Med Univ, Hosp 2, Hefei, Peoples R China; [Lei, Chen] Ningxia Med Univ, Gen Hosp, Yinchuan, Peoples R China; [Guo, Shuren] Shandong Boan Biotechnol Co Ltd, Yantai, Peoples R China"

通信作者:"Zhang, ZL (通讯作者),Shanghai Jiao Tong Univ, Shanghai Clin Res Ctr Bone Dis, Dept Osteoporosis & Bone Dis, Peoples Hosp 6, Shanghai 200233, Peoples R China."












关键词:Biosimilar; Denosumab; Osteoporosis; Bone mineral density

摘要:"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 telo-peptide 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 (R). 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 (R). The presented results are encouraging and can offer some valuable evidence for the clinical practice."