Shanghai, China, November 9th, 2020 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient was dosed in a Phase 1 clinical trial of the company?s denosumab biosimilar HLX14, a recombinant anti-RANKL fully human monoclonal antibody injection. HLX14 was independently developed by Henlius with the denosumab originator as reference drug, and the development is in accordance with the NMPA and EMA biosimilar guidelines. It can be potentially used for the treatment of postmenopausal women with osteoporosis at high risk for fracture.

In China, osteoporosis has become a severe health problem for people over 50 years old, especially for middle and aged women. More than one third of women over 50 years old are suffering from osteoporosis^[1]. Health problems caused by osteoporosis, like facture, can result in significant loss of quality of life. Nonetheless, the percentage of patients with osteoporosis that have received standardized treatment is relatively low. With the increasing patient number and improved diagnosis of osteoporosis in China, the huge unmet medical needs in the treatment of osteoporosis are urgently to be addressed^[2]. HLX14 can specifically bind to RANKL (receptor activator of nuclear factor kappa B ligand) and block the interaction between RANKL and RANK, which is expressed on the surface of osteoclasts, thus inhibiting RANKL/RANK-mediated differentiation, maturation and activation of osteoclasts, thereby reducing bone resorption and the incidence of skeletal-related events^[3]. Denosumab has been approved for the treatment of postmenopausal women with osteoporosis at high risk for fracture and giant cell tumor of bone by NMPA. Additional indication of denosumab has been approved in the United States and the European Union, which is for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.

Following the principles of stepwise development, comparability and similarity assessment, HLX14 has been compared with the denosumab originator via a series of head-to-head non-clinical studies. As a result, HLX14 was shown to be highly similar to denosumab in pre-clinical pharmacology, toxicology and pharmacokinetic studies, suggesting potential benefits for osteoporosis patients at high risk of fracture. This is a Phase 1 clinical study of HLX14 in healthy male volunteers conducted in two parts. Part 1 is an open-label, randomised, parallel-controlled, single-dose, two-arm pilot study aimed to compare the pharmacokinetics, pharmacodynamics, safety, tolerability and immunogenicity of HLX14 and EU-sourced denosumab administered via subcutaneous injection. Part 2 is a double-blind, randomised, parallel-controlled, single-dose, four-arm study primarily aimed to establish the pharmacokinetic bioequivalence of HLX14 and US-, EU-, CN-sourced denosumab (hereinafter referred to as the ?reference drug?). The secondary objective of Part 2 is to evaluate the similarity of pharmacodynamics, safety, tolerability and immunogenicity between HLX14 and the reference drug. Results from this Phase 1 study will provide reference for dosing scheme in the following clinical studies of HLX14.

[1] 2018???????????????. http://www.nhc.gov.cn/wjw/zcjd/201810/4988546cfa1040db86c1815d3dad7a2b.shtml

[2] Lin X, Xiong D, Peng Y-Q, et al. Epidemiology and management of osteoporosis in the People?s Republic of China: current perspectives. Clin Interv Aging. 2015;10:1017?1033.

[3] Romas E. Clinical applications of RANK-ligand inhibition. Intern Med J 2009;39:110?6.