Organon announced that the U.S. Food and Drug Administration (FDA) has accepted its Biologic License Application (BLA) for HLX14, an investigational biosimilar of denosumab (Prolia/Xgeva; Amgen). Denosumab, a bone anti-resorptive medication, is prescribed for osteoporosis and other bone-related disorders, including bone metastases from solid tumors, osteoporosis in postmenopausal women at high fracture risk, and glucocorticoid-induced bone loss in men.
HLX14 is a fully human immunoglobulin G2 monoclonal antibody that targets the receptor activator of NF-κB ligand (RANKL). By binding to RANKL, HLX14 prevents it from interacting with its receptor, thus inhibiting osteoclast maturation and bone resorption.
The BLA submission is supported by data from head-to-head studies, including comparative quality analytical studies and two clinical studies. The first study was a two-part Phase 1 trial in healthy Chinese adult males. Part 1 was an open-label, randomized study, while Part 2 was a double-blinded, randomized study. Part 1 focused on pharmacokinetic parameters, comparing HLX14 with EU-sourced Prolia. Part 2 aimed to compare the pharmacokinetic similarity of HLX14 with Prolia sourced from the US, EU, and China.
The second study was a randomized, double-blind Phase 3 clinical trial that evaluated the efficacy, safety, tolerability, and immunogenicity of HLX14 compared to EU-sourced reference product in postmenopausal women with osteoporosis at high risk of fracture. The trial included 478 women who were randomized 1:1 to receive either HLX14 or the reference product. Participants received subcutaneous injections every six months over a 546-day treatment period, following a 28-day screening period.
The primary endpoints were efficacy and pharmacodynamic outcomes at 52 weeks. Secondary endpoints included secondary efficacy and pharmacodynamic assessments at 78 weeks. The study met its primary endpoints, demonstrating comparable percentage change in bone mineral density at the lumbar spine and similar effect-time curve for percentage change of serum type I collagen C-telopeptide.
Current Market Landscape
In March 2024, the FDA approved two denosumab biosimilars from Sandoz, marking the first FDA-approved biosimilars for denosumab, indicated for all of the reference product's uses. These biosimilars are also approved as interchangeable for Prolia and Xgeva for all their approved indications. The acceptance of the BLA for HLX14 represents another potential option for patients requiring denosumab treatment.
