FDA Approves 2 Denosumab Biosimilars for Osteoporosis and Cancer-Related Bone Disease

The FDA has approved the biosimilars denosumab-bmwo (Stobloco) and (Osenvelt), referencing denosumab (Prolia) and (Xgeva), respectively, for use in all indications of the reference products.1

Stobloco is indicated for postmenopausal women with osteoporosis at high risk for fracture; to increase bone mass in men with osteoporosis at high risk for fracture or in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer; for glucocorticoid-induced osteoporosis in men and women at high risk for fracture; and to increase bone mass in women at high risk for fracture receiving an adjuvant aromatase inhibitor therapy for breast cancer.

Osenvelt 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 the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

“Denosumab is used to improve or protect bone health in patients with osteoporosis or those undergoing various cancer treatments and as a therapy for a lifetime for postmenopausal [patients with] osteoporosis,” Jean-Yves Reginster, MD, PhD, professor of medicine and Protein Research chair in Biochemistry Department in the College of Science at King Saud University; and director of the WHO Collaborating Centre for Epidemiology of Musculoskeletal Health and Aging, stated in a news release. "Biosimilars have expanded into new therapeutic areas such as immunology, oncology and ophthalmology as they continue to offer significant cost-saving potential while expanding patient access. Having a denosumab product with a clinically proven track record in quality and safety is a valuable addition for my patients.”

These regulatory decisions were supported by data from a phase 3 trial (NCT04757376) evaluating the efficacy, pharmacodynamics (PD), pharmacokinetics (PK), safety, and immunogenicity of CT-P41 (denosumab-bmwo) compared with reference denosumab.

The study met its primary end point. The least squares (LS) mean difference in lumbar spine bone mineral density (BMD) percent change from baseline at week 52 fell within the predefined equivalence margin in both the full analysis set (–0.139; 95% CI, –0.826 to 0.548) and the per-protocol set (–0.280; 95% CI, –0.973 to 0.414).2

The primary PD end point, measured as the geometric LS mean ratio for serum carboxy-terminal cross-linking telopeptide of type I collagen through week 26, was 94.94% (95% CI, 90.75%-99.32%), meeting the predefined 80% to 125% equivalence criteria.

Secondary efficacy, PD, PK, and safety outcomes remained comparable across all treatment groups throughout the 78-week study period, including in patients who transitioned from US-denosumab to CT-P41 after week 52.

The double-blind, randomized, active-controlled phase 3 trial was conducted over 78 weeks to evaluate the efficacy, PD, and safety of CT-P41 in postmenopausal women with osteoporosis. The trial consisted of two treatment periods and aimed to assess both initial treatment efficacy and the impact of switching from reference denosumab to CT-P41.

A total of 479 patients were enrolled and randomly assigned 1:1 to receive 60 mg subcutaneous CT-P41 or denosumab. At Week 52, patients initially assigned to CT-P41 continued treatment. Patients who had received reference denosumab were randomly assigned again in a 1:1 fashion to either continue denosumab or switch to CT-P41 for the remaining 26 weeks.

The primary efficacy end point was the percent change from baseline in lumbar spine BMD at week 52.

In a phase 1 study (NCT06037395), the primary and secondary PK, PD, safety, and immunogenicity results were comparable between CT-P41 and reference denosumab. Ninety percent CIs for ratios of geometric LS means were within the predefined equivalence margin for AUC0-inf (100.4%-114.7%), AUC0-last (99.9%-114.3%), and Cmax (95.2%-107.3%).3

The double-blind, two-arm, parallel-group study included healthy Asian adult males who were randomly assigned 1:1 to receive CT-P41 or reference denosumab.

References

1. Celltrion receives U.S. FDA approval for Stoboclo (denosumab-bmwo) and Osenvelt (denosumab-bmwo) biosimilars referencing Prolia and Xgeva. Celltrion. March 4, 2025. Accessed March 4, 2025. https://www.celltrion.com/en-us/company/media-center/press-release/3768
2. Reginster JY, Czerwinski E, Wilk K, et al. Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, active-controlled, Phase 3 trial in postmenopausal women with osteoporosis. Osteoporosis international. 2024;35(11):1919-1930. doi:https://doi.org/10.1007/s00198-024-07161-x
3. Kim A, Hong JH, Shin W, et al. A randomized, double-blind, single-dose, phase 1 study comparing the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of denosumab biosimilar CT‑P41 and reference denosumab in healthy males. Expert Opin Biol Ther. 2024;24(7):655-663. doi:10.1080/14712598.2024.2316846