Denosumab Biosimilars Win FDA, EU Approvals for Select Cancer-Related Bone Loss

The FDA has approved denosumab-dssb biosimilars (Ospomyv, a 60-mg prefilled syringe; and Xbryk, a 120-mg vial) for use in all indications of the respective previously approved reference drugs Prolia and Xgeva.1 Additionally, the European Commission (EC) has approved the denosumab biosimilars Obodence (60-mg prefilled syringe) and Xbryk for use in the same indications as the reference drugs Prolia and Xgeva, respectively.2

In the United States (US), Ospomyv is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture; to increase bone mass in men with osteoporosis at high risk for fracture; for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture; to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer; and to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.1 Xbryk is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors; the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity; and for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

“The FDA approval of Ospomyv and Xbryk marks a key step in improving patient access and alleviating treatment cost for patients with osteoporosis and cancer-related bone loss in the US. By providing quality-proven biosimilars, we are helping to address a critical health care need and reduce the burden of skeletal fractures that impact patients’ quality of life,” Byoungin Jung, vice president and Regulatory Affairs team leader at Samsung Bioepis, stated in a news release. “This achievement underscores our commitment to health care innovation through biosimilars and our mission to meet the growing needs in critical therapeutic areas.”

In the European Union (EU), Obodence is indicated for the treatment of osteoporosis in postmenopausal women and in men at increased risk of fractures; treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures; and treatment of bone loss associated with long-term systemic glucocorticoid therapy in adult patients at increased risk of fracture.2 Xbryk is approved for the prevention of skeletal-related events in adults with advanced malignancies involving bone; and the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

The regulatory decisions by the FDA and EC were supported by data from a randomized, double-blind, 3-arm phase 1 trial (NCT06095427) that evaluated a denosumab biosimilar (LY06006) vs US- and EU-sourced denosumab in healthy male patients.

Findings published in Expert Opinion on Drug Metabolism & Toxicology demonstrated that LY06006 generated similar pharmacokinetic (PK), pharmacodynamic, safety, and immunogenicity outcomes compared with denosumab.3 The 90% confidence intervals (CIs) for geometric least squares mean ratios all fell within the predetermined equivalence margin for area under the concentration time curve (AUC) from time 0 to infinity (AUC0-inf; 89.0%-111.1%), AUC from 0 to last quantifiable concentration (AUC0-t; 89.7%-111.3%), and maximum serum concentration (Cmax; 92.3%-106.7%).

During the study, 300 healthy male patients were randomly assigned 1:1:1 to receive a single 60-mg subcutaneous dose of LY06006, US-sourced denosumab, or EU-sourced denosumab.

Cmax, AUC0-t, and AUC0-inf served as the trial’s primary PK end points. PK equivalence was based on the 2-sided 90% CI for the geometric least squares mean ratio falling between 80% and 125%.

“With this [EU] approval for a biosimilar, a cost-effective treatment option with equal clinical effectiveness and safety compared to the reference medicine, we are making an important progress towards enhancing access to an effective treatment option for patients with osteoporosis and cancer-related bone loss, which can lead to skeletal fractures, seriously affecting the quality of life of patients,” Jung stated in another news release.2 “This milestone reflects our passion for health and our continued focus on advancing biosimilar innovation and meeting the growing health care needs in vital therapeutic areas.”

References

1. FDA approves Samsung Bioepis’ Ospomyv, Xbryk (denosumab-dssb), a biosimilar to Prolia and Xgeva. News release. Samsung Bioepis. February 16, 2025. Accessed February 17, 2025. https://www.samsungbioepis.com/en/newsroom/newsroomView.do?idx=435&currentPage=1
2. Samsung Bioepis gains European Commission (EC) approval for denosumab biosimilar (Obodence, Xbryk). News release. Samsung Bioepis. February 16, 2025. Accessed February 17, 2025. https://www.samsungbioepis.com/en/newsroom/newsroomView.do?idx=436&currentPage=1
3. Fuhr R, Sun X, Wang X, et al. A three-arm clinical study to compare pharmacokinetic and pharmacodynamic similarity of the denosumab biosimilar LY06006 with reference denosumab in healthy male subjects. Expert Opin Drug Metab Toxicol. Published online November 24, 2024. doi:10.1080/17425255.2024.2432673