Shanghai Henlius Biotech and Organon announced that the European Medicines Agency has validated the marketing authorization applications for HLX14, an investigational biosimilar to denosumab targeting the treatment of osteoporosis in postmenopausal women at high risk for fracture. The validation represents a significant regulatory milestone for the companies' efforts to expand access to this bone-protective therapy.
Clinical Development Success
The marketing authorization application submissions were based on data from a phase 3 study (NCT05352516) that compared the efficacy, safety, tolerability, and immunogenicity of HLX14 with European Union-sourced reference denosumab in postmenopausal women with osteoporosis. In April 2024, Shanghai Henlius Biotech and Organon announced that the trial met both its primary efficacy and pharmacodynamic endpoints.
The randomized, double-blind, international, multicenter, parallel-controlled trial enrolled ambulatory postmenopausal women with osteoporosis between 60 and 90 years of age. Postmenopausal status was defined as more than 2 years of menopause, and patients were required to have a bone mineral density T-score between −2.5 and −4.0 at the lumbar spine or total hip.
Study Design and Endpoints
Eligible patients were stratified according to body mass index and geographic region, then randomly assigned 1:1 to receive either 60 mg of HLX14 or reference denosumab through subcutaneous injection every 6 months for a total of 3 doses.
The study's primary endpoints were the percentage change in bone mineral density at the lumbar spine from baseline to week 52 assessed by central imaging, and area under the effect-time curve for percentage change of serum type I collagen C-telopeptide from baseline to week 26.
Secondary efficacy endpoints included percent changes from baseline in bone mineral density at the lumbar spine, total hip, and femoral neck at various time points through week 78, as well as fracture rates from baseline to weeks 52 and 78.
Mechanism of Action and Market Need
Denosumab is a human monoclonal IgG2 antibody that has high affinity and specificity for RANKL. After binding to the RANK receptor on the surface of osteoclast precursors and osteoclasts, it prevents the interaction of RANKL/RANK, leading to decreased bone resorption in cortical and trabecular bone as osteoclasts are unable to form, function, or survive.
The biosimilar addresses a substantial medical need, as it was estimated that 32 million Europeans ages 50 or above had osteoporosis in 2019, with 25.5 million of these patients being women. Denosumab has been approved in various countries and regions under different trade names including Prolia and Xgeva for a range of indications, particularly for the treatment of osteoporosis in postmenopausal women at high risk for fracture.
