Denosumab biosimilar HLX14 versus EU-denosumab in postmenopausal women at high fracture risk: a randomized, double-blind, multicenter phase 3 trial
Year: 2026
Type: article
Abstract: Biosimilars can increase access to efficacious drugs. This randomized, double-blind phase 3 study demonstrated efficacy equivalence between HLX14 and EU-denosumab and comparable safety, pharmacokinetics, and immunogenicity in postmenopausal women with osteoporosis at high risk of fracture. The findings provided direct evidence for HLX14 as a potential denosumab biosimilar. HLX14 is a proposed biosimilar of denosumab. This randomized, double-blind, multicenter, parallel-controlled phase 3 study aimed to compare the equivalence between HLX14 and European Union-sourced denosumab (EU-denosumab). Elderly female subjects with osteoporosis at high risk of fracture were randomized to receive two doses of HLX14 or EU-denosumab. At Week 52, subjects receiving EU-denosumab were re-randomized 1:1 to continue with a third dose of EU-denosumab or switch to HLX14, while those receiving HLX14 continued with a third dose of the drug. The co-primary endpoints were the percent change from baseline in lumbar spine BMD (LS-BMD) at Week 52, and the area under the effect-time curve for percent change of serum type I collagen C-telopeptide from baseline to Week 26 (AUEC 0-26W ). Initially, 514 subjects were enrolled (256 vs. 258) across 40 hospitals in China. An increase in LS-BMD was evident in both groups (6.10% vs. 5.90%) at Week 52. The adjusted mean difference was 0.23% (90% confidence interval [CI]: −0.36%, 0.83%; 95% CI: −0.48%, 0.95%), demonstrating efficacy equivalence as the 95% and 90% CIs fell within the pre-specified equivalence margins of −1.45% to 1.45%. Similarly, pharmacodynamic equivalence was shown with the 95% and 90% CIs for the geometric mean ratio of AUEC 0-26W (1.01, 90% CI: 0.99, 1.04; 95% CI: 0.98, 1.05) fully contained within the equivalence margins of 0.8 to 1.25. The results of all secondary efficacy endpoints also supported the equivalence between HLX14 and EU-denosumab. Safety profiles were comparable and remained similar even after the single switch of treatment. The findings from this phase 3 study support biosimilarity between HLX14 and denosumab. This trial was registered at Clinicaltrials.gov (NCT05352516).
Source: Osteoporosis International
Authors: Li Xin, Zhiyong Li, Jun Zhang, Qun Xia, Ping Jin, Qingyun Xue, Xin Zheng, Xin Tang, Zhong Yuan, Lin Shen, Peng Duan, Yawei Zhang, Yanan Huo, Bingwu Wang, Zhifeng Cheng, Youliang Cao, Liping Li, Yuhong Zeng, Lizhen Lan, Yibing Lu, Li Mao, Zhan Zhang, Cong Chen, Qingyu Wang, Haoyu Yu, Jing Li, Jun Zhu
Institutions: Affiliated Hospital of Xuzhou Medical College, Zhejiang Provincial People's Hospital, Tianjin First Center Hospital, Third Xiangya Hospital, Beijing Geriatric Hospital, Beijing Hospital, West China Hospital of Sichuan University, Wuhan Union Hospital, Huazhong University of Science and Technology, Third Hospital of Nanchang, Jiangxi Pingxiang People's Hospital, Jiangxi Provincial People's Hospital, Weifang People's Hospital, Harbin Medical University, Fourth Affiliated Hospital of Harbin Medical University, Third People's Hospital of Yunnan Province, First Affiliated Hospital of Henan University of Science and Technology, Xi'an Honghui Hospital, Xi'an Jiaotong University, Shanxi Medical University, First Hospital of Shanxi Medical University, Second Affiliated Hospital of Nanjing Medical University, Huaian First People’s Hospital
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,090
OpenAlex ID: W7225227351