PMID- 36381249
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221117
IS  - 2214-031X (Print)
IS  - 2214-0328 (Electronic)
IS  - 2214-031X (Linking)
VI  - 38
DP  - 2023 Jan
TI  - Denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women: A 
      randomized, double-blind, placebo-controlled, multicenter phase III study.
PG  - 117-125
LID - 10.1016/j.jot.2022.06.007 [doi]
AB  - 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(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.
CI  - (c) 2022 The Author(s).
FAU - Gu, Jiemei
AU  - Gu J
AD  - Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and 
      Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 
      Shanghai, 200233, PR China.
FAU - Zhang, Hao
AU  - Zhang H
AD  - Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and 
      Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 
      Shanghai, 200233, PR China.
FAU - Xue, Qingyun
AU  - Xue Q
AD  - Beijing Hospital, PR China.
FAU - Wang, Li
AU  - Wang L
AD  - Tianjin Hospital, PR China.
FAU - Cheng, Zhifeng
AU  - Cheng Z
AD  - Fourth Affiliated Hospital of Harbin Medical University, PR China.
FAU - Zhang, Yawei
AU  - Zhang Y
AD  - Jiangxi Pingxiang People's Hospital, PR China.
FAU - Li, Qifu
AU  - Li Q
AD  - The First Affiliated Hospital of Chongqing Medical University, PR China.
FAU - Yuan, Lingqing
AU  - Yuan L
AD  - The Second Xiang-ya Hospital, Central South University, PR China.
FAU - Li, Yukun
AU  - Li Y
AD  - Third Hospital of Hebei Medical University, PR China.
FAU - Dong, Jin
AU  - Dong J
AD  - First Hospital of Shanxi Medical University, PR China.
FAU - Huo, Yanan
AU  - Huo Y
AD  - Jiangxi Provincial People's Hospital, PR China.
FAU - Tang, Xin
AU  - Tang X
AD  - West China School of Medicine, West China Hospital of Sichuan University, PR 
      China.
FAU - Hu, Ling
AU  - Hu L
AD  - The First Hospital of Nanchang, PR China.
FAU - Wang, Xinjia
AU  - Wang X
AD  - The Second Affiliated Hospital of Shantou University Medical College, PR China.
FAU - Hua, Fei
AU  - Hua F
AD  - The First People's Hospital of Changzhou, PR China.
FAU - Shen, Lin
AU  - Shen L
AD  - Union Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, PR China.
FAU - Cheng, Jinluo
AU  - Cheng J
AD  - Changzhou No. People's Hospital, PR China.
FAU - Zhou, Huimin
AU  - Zhou H
AD  - The First Hospital of Hebei Medical University, PR China.
FAU - Xu, Youjia
AU  - Xu Y
AD  - The Second Affiliated Hospital of Soochow University, PR China.
FAU - Yang, Tao
AU  - Yang T
AD  - Chongqing University Three Gorges Hospital, PR China.
FAU - Wang, Chuansuo
AU  - Wang C
AD  - The First Affiliated Hospital of Hainan Medical College, PR China.
FAU - Xu, Jin
AU  - Xu J
AD  - Shandong Provincial Hospital, PR China.
FAU - Shen, Jie
AU  - Shen J
AD  - Shunde Hospital of Southern Medical University, PR China.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - The Third Affiliated Hospital of Guangzhou Medical University, PR China.
FAU - Zhang, Xiaomei
AU  - Zhang X
AD  - The First Affiliated Hospital of Bengbu Medical College, PR China.
FAU - Hong, Dun
AU  - Hong D
AD  - Taizhou Hospital of Zhejiang Province, PR China.
FAU - Guan, Xiaoling
AU  - Guan X
AD  - Shandong Provincial Qianfoshan Hospital, PR China.
FAU - Xiao, Xinhua
AU  - Xiao X
AD  - The First Affiliated Hospital of University of South China, PR China.
FAU - Wang, Guang
AU  - Wang G
AD  - Capital Medical University Affiliated Beijing Chao-Yang Hospital, PR China.
FAU - Liu, Yonghua
AU  - Liu Y
AD  - The Third Hospital of Nanchang, PR China.
FAU - Fu, Liujun
AU  - Fu L
AD  - The First Affiliated Hospital of Henan University of Science and Technology, PR 
      China.
FAU - Chen, Jianting
AU  - Chen J
AD  - Nanfang Hospital of Southern Medical University, PR China.
FAU - Cheng, Xigao
AU  - Cheng X
AD  - The Second Affiliated Hospital of Nanchang University, PR China.
FAU - Ding, Yue
AU  - Ding Y
AD  - Sun Yat-sen Memorial Hospital,Sun Yat-sen University, PR China.
FAU - Liu, Lijun
AU  - Liu L
AD  - Yiyang Central Hospital, PR China.
FAU - Yao, Qi
AU  - Yao Q
AD  - Ningbo First Hospital, PR China.
FAU - Zhang, Xinchao
AU  - Zhang X
AD  - Jinshan Hospital of Fudan University, PR China.
FAU - Li, Lixin
AU  - Li L
AD  - Xiamen Hospital of T.C.M, PR China.
FAU - Zhang, Panjun
AU  - Zhang P
AD  - Yixing People's Hospital, PR China.
FAU - Deng, Chunying
AU  - Deng C
AD  - Zigong Fourth People's Hospital, PR China.
FAU - Jiang, Chengyan
AU  - Jiang C
AD  - The First People's Hospital of Zunyi, PR China.
FAU - You, Li
AU  - You L
AD  - Shanghai General Hospital, PR China.
FAU - Wang, Kai
AU  - Wang K
AD  - Taizhou Hospital of TCM, PR China.
FAU - Zhang, Shimin
AU  - Zhang S
AD  - Yangpu Hospital,Tongji University, PR China.
FAU - Xiao, Jianzhong
AU  - Xiao J
AD  - Beijing Tsinghua Changgung Hospital, PR China.
FAU - Liu, Wei
AU  - Liu W
AD  - Nantong First People's Hospital, PR China.
FAU - Du, Xiaohong
AU  - Du X
AD  - The First Affiliated Hospital of Wenzhou Medical University, PR China.
FAU - Shang, Xianwen
AU  - Shang X
AD  - The Affiliated Hospital of Guizhou Medical University, PR China.
FAU - Pan, Tianrong
AU  - Pan T
AD  - The Second Hospital of Anhui Medical University, PR China.
FAU - Lei, Chen
AU  - Lei C
AD  - General Hospital of Ningxia Medical University, PR China.
FAU - Guo, Shuren
AU  - Guo S
AD  - Shandong Boan Biotechnology Co., Ltd., PR China.
FAU - Zhang, Zhenlin
AU  - Zhang Z
AD  - Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and 
      Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 
      Shanghai, 200233, PR China.
LA  - eng
PT  - Journal Article
DEP - 20221029
PL  - Singapore
TA  - J Orthop Translat
JT  - Journal of orthopaedic translation
JID - 101625127
PMC - PMC9633870
OTO - NOTNLM
OT  - Biosimilar
OT  - Bone mineral density
OT  - Denosumab
OT  - Osteoporosis
EDAT- 2022/11/17 06:00
MHDA- 2022/11/17 06:01
PMCR- 2022/10/29
CRDT- 2022/11/16 02:50
PHST- 2022/01/19 00:00 [received]
PHST- 2022/06/11 00:00 [revised]
PHST- 2022/06/23 00:00 [accepted]
PHST- 2022/11/16 02:50 [entrez]
PHST- 2022/11/17 06:00 [pubmed]
PHST- 2022/11/17 06:01 [medline]
PHST- 2022/10/29 00:00 [pmc-release]
AID - S2214-031X(22)00067-5 [pii]
AID - 10.1016/j.jot.2022.06.007 [doi]
PST - epublish
SO  - J Orthop Translat. 2022 Oct 29;38:117-125. doi: 10.1016/j.jot.2022.06.007. 
      eCollection 2023 Jan.