A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk
Hao Zhang1,
Jie-mei Gu1,
Ai-jun Chao2,
Qun Cheng3,
Dong-hui Teng4,
Jin-ming Yu5,
Bing-wu Wang6,
Ya-nan Huo7,
Li Mao8,
Qiu Zhang9,
Hong Yang10,
Shi-gui Yan11,
Ke-qin Zhang12,
Xue-ling Zhao13,
Hua Lin14,
Yu Pei15,
Zhong Yuan16,
Ru-chun Dai17,
Liang He18,
Li Chen19,
Yong-feng Su20,
Zhong-liang Deng21,
Li You22,
Bo Ban23,
Mei Zhu24,
You-liang Cao25,
Yi-kun Zhu26,
Zhi-jun Li27,
Zhi Zhang28,
Cheng-qing Yi29,
Yi-bing Lu30,
Guang Wang31,
Cui-cui Han32,
Zhen-jiang Wang33,
Xian-xing Li34,
Zhen-lin Zhang1
1 Department of Osteoporosis and Bone Diseases, Shanghai Clinical Research Center of Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
2 Department of Osteo-Internal, Tianjin Hospital, Tianjin 300211, China
3 Department of Osteoporosis, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
4 Department of Orthopedics, Tianjin First Central Hospital, Tianjin 300192, China
5 Department of Endocrinology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530016, China
6 Department of Spine Surgery, Weifang People’s Hospital, Weifang 261000, China
7 Department of Endocrinology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 330006, China
8 Department of Endocrinology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian 223300, China
9 Department of Endocrinology, The First Affillated Hospital of Anhui Medical University, Hefei 230022, China
10 Department of Endocrinology, Ruian People’s Hospital, Wenzhou 325200, China
11 Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
12 Department of Endocrinology, Tongji Hospital of Tongji University, Shanghai 200065, China
13 Department of Orthopedics, First Affillated Hospital of Kunming Medical University, Kunming 650032, China
14 Metabolic Bone Disease Prevention and Treatment Research Center, Nanjing Drum Tower Hospital, Nanjing 210008, China
15 Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
16 Department of Osteoporosis, Nanchang Hongdu Hospital of TCM, Nanchang 330006, China
17 Department of Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
18 Department of Orthopedics, Beijing Jishuitan Hospital, Beijing 100035, China
19 Department of Endocrinology, Qilu Hospital of Shandong University, Jinan 250012, China
20 Department of Endocrinology, Inner Mongolia Baogang Hospital, Baotou 014010, China
21 Department of Spine Surgery, The second affiliated hospital of Chongqing medical university, Chongqing 400010, China
22 Department of Endocrinology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China
23 Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining 272007, China
24 Department of Endocrinology, Tianjin Medical University General Hospital, Tianjin 300052, China
25 Department of Orthopedics, The Third People’s Hospital of Yunnan Province, Kunming 650011, China
26 Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030001, China
27 Department of Rheumatology and Immunology, The First Affillated Hospital of Bengbu Medical College, Bengbu 233004, China
28 Department of Spine Surgery, Suining Central Hospital, Suining 629000, China
29 Department of Orthopedics, Shanghai Pudong Hospital, Shanghai 201399, China
30 Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China
31 Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
32 Department of Medical, Qilu Pharmaceutical Co., Ltd, Jinan 250100, China
33 Department of Project, Qilu Pharmaceutical Co., Ltd, Jinan 250100, China
34 Department of Statistical analysis, Qilu Pharmaceutical Co., Ltd, Jinan 250100, China
Correspondence to: Zhen-lin Zhang: zhangzl@sjtu.edu.cn,
DOI: 10.1038/s41401-022-00954-y
Received: 6 January 2022
Accepted: 4 July 2022
Advance online: 27 July 2022
Abstract
The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): −77.352% (−87.080%, −66.844%), and N-terminal procollagen of type l collagen (P1NP): −50.867% (−57.184%, −45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.
Keywords:
denosumab biosimilar; postmenopausal osteoporosis; Chinese women; bone mineral density; bone turnover markers; adverse events
