FDA Approves Third Pair of Denosumab Biosimilars

The FDA today approved Celltrion's Steoboclo and Osenvelt (CT-P41; denosumab-bmwo) for all indications of the reference products (Prolia and Xgeva, respectively).¹ The approval marks the third for denosumab biosimilars, expanding access to lower-cost biologics for the treatment of osteoporosis and bone metastases.²

Denosumab is a monoclonal antibody that inhibits the RANKL protein, a key driver of bone breakdown, helping to prevent bone loss, strengthen bones, enhance bone density, and reduce the risk of fractures in patients with osteoporosis and bone metastases. | Image credit: crevis - stock.adobe.com

Denosumab is a monoclonal antibody that inhibits the RANKL protein, a key driver of bone breakdown. By preventing bone loss, it strengthens bones, enhances bone density, and reduces the risk of fractures in patients.

These products are usually approved under 2 distinct names, each linked to a specific indication. Stoboclo corresponds with Prolia, which is prescribed for osteoporosis patients, while Osenvelt references Xgeva, used for treating and preventing bone fractures in patients at higher risk due to bone metastases.

The fresh approval comes nearly a year after the first approval for a denosumab biosimilar.³ Wyost and Jubbonti (denosumab-bddz) were approved in early March 2024, and Ospomyv and Obodence (denosumab-dssb) in February 2025.² Additionally, the European Commission granted approval for Stoboclo and Osenvelt in late February 2025.⁴

The approval was based on robust evidence from a phase 3 trial (NCT04757376) over 78 weeks evaluating the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of CT-P41 vs reference denosumab.⁵ The study was a double-blind, randomized, active-controlled clinical trial conducted at 20 sites across 4 countries.

Researchers studied 440 postmenopausal women with osteoporosis and found that CT-P41 and US-sourced denosumab were equally effective in improving lumbar spine bone mineral density (BMD) at week 52. Both treatments also showed similar improvements in hip and femoral neck BMD, fracture rates, and quality of life scores.

Safety profiles were comparable, demonstrating a low incidence of antidrug antibodies and serious adverse events. However, limitations included smaller sample sizes in some groups and external disruptions that impacted patient visits and dosing. Despite these, the findings support CT-P41 as a safe and effective alternative to US-sourced denosumab.

"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," Jean-Yves Reginster, MD, PhD, director of the WHO Collaborating Centre for Epidemiology of Musculoskeletal Health and Aging, said in a statement.¹

Stoboclo and Osenvelt are anticipated to launch in the US in June 2025 as part of a settlement agreement with Amgen, the reference product manufacturer.

References

1. Celltrion receives U.S. FDA approval for Stoboclo (denosumab-bmwo) and Osenvelt^® (denosumab-bmwo) biosimilars referencing Prolia and Xgeva. Press release. Celltrion; March 3, 2025. Accessed March 4, 2025. https://www.prnewswire.com/news-releases/celltrion-receives-us-fda-approval-for-stoboclo-denosumab-bmwo-and-osenvelt-denosumab-bmwo-biosimilars-referencing-prolia-and-xgeva-302390957.html

2. Jeremias S. FDA, EMA approve second pair of denosumab biosimilars. The Center for Biosimilars^®. February 17, 2025. Accessed March 4, 2025. https://www.centerforbiosimilars.com/view/fda-ema-approve-second-pair-of-denosumab-biosimilars

3. Jeremais S. FDA approves first denosumab biosimilars. The Center for Biosimilars. March 5, 2024. Accessed March 4, 2025. https://www.centerforbiosimilars.com/view/fda-approves-first-denosumab-biosimilar

4. Jeremias S. EC approves Celltrion denosumab, aflibercept biosimilars. The Center for Biosimilars. February 20, 2025. Accessed March 4, 2025. https://www.centerforbiosimilars.com/view/ec-approves-celltrion-denosumab-aflibercept-biosimilars

5. Jeremias S. Equivalence confirmed: CT-P41 paves the way for affordable osteoporosis care. The Center for Biosimilars. January 8, 2025. Accessed March 4, 2025. https://www.centerforbiosimilars.com/view/equivalence-confirmed-ct-p41-paves-the-way-for-affordable-osteoporosis-care