Henlius Begins Phase 3 Trials for Denosumab Biosimilar

Shanghai Henlius Biotech announced the commencement of an international multicenter phase 3 clinical trial for its denosumab biosimilar candidate (HLX14), a recombinant monoclonal antibody injection that helps to prevent fractures related to osteoporosis.

The news comes after Henlius entered into a licensing agreement with Organon over HLX14 and HLX11, a pertuzumab biosimilar, that will enable commercialization of the biosimilars in the United States, the European Union, Japan, and other emerging markets.

Originator denosumab is used for a range of indications, including osteoporosis with a high risk of fracture, giant cell tumor of bone, and skeletal-related events in multiple myeloma or bone metastases from solid tumors. Denosumab binds to receptor activator of nuclear factor kappa B ligand (RANKL) and blocks RANKL and RANK from interacting, both of which are overexpressed on the surface of osteoclasts. Inhibiting the interaction between RANKL and RANK can prevent activation osteoclasts, reduce bone resorption, and lower the incidence of skeletal-related events.

In China, osteoporosis is a significant health issue for people 50 years and older, and over one-third of the female population over the age of 50 has been diagnosed with the condition. Fractures caused by osteoporosis can lead to a decrease in patient quality of life, and the percentage of patients with osteoporosis in China who have received standardized treatment is relatively low.

“With the increasing patient number and improved diagnosis of osteoporosis, the huge unmet medical needs in the treatment of osteoporosis are urgently to be addressed,” wrote Henlius representatives in a statement on the trial commencement.

The randomized, double-blind, parallel-controlled study will aim to demonstrate comparable efficacy, safety, tolerability, and immunogenicity profiles of HLX14 and the reference product in postmenopausal women with osteoporosis at high risk of fracture. Enrolled patients have been randomized to receive subcutaneous injections of the biosimilar or the reference product for 6 months for 2 cycles.

The researchers will assess the percentage change from baseline to day 365 of bone mineral density (BMD) at the lumbar spine as the primary end point. In addition to safety, pharmacokinetics, and immunogenicity, the secondary endpoints are the change in BMD at the total hip from baseline to 1-year; the change in BMD at femoral neck from baseline to 1-year; and change in serum type 1 collagen C-telopeptide and serum procollagen type 1 N-telopeptide from base to day 29, day 92, day 274, and day 365.

In June 2020, China’s National Medical Products Administration approved HLX14 for use in postmenopausal osteoporosis.

However, Henlius isn’t the only company developing a denosumab biosimilar. Samsung Bioepis began a phase 3 trial for its candidate in December 2020 and Celltrion Healthcare started testing its candidate in a phase 1 trail in August 2020. JHL Biotech began a phase 1 trial for its denosumab biosimilar in May 2020. Neuclone, an Australian biosimilar developer, also announced that it was in the process of developing a denosumab biosimilar candidate in 2018.