FDA, EMA Approve Second Pair of Denosumab Biosimilars

Nearly a year after the FDA approved the first denosumab biosimilars, the agency, along with the European Medicines Agency (EMA), announced the approval of 2 more biosimilars (denosumab-dssb; SB16) referencing Prolia/Xgeva (denosumab).^1,2,3

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SB16 will be marketed as Ospomyv in the US and Obodence in Europe when indicated for the treatment or prevention of osteoporosis, and Xbryk in both regions when used to prevent skeletal fractures in patients with bone metastases.^2,3 Additionally, Ospomyv/Obodence will be available as a 60-mg prefilled syringe, and Xbryk will be offered in a 120-mg vial.

The FDA granted interchangeability for Ospomyv and Xbryk, allowing them to be substituted for their respective reference products at the pharmacy level without needing to wait for a provider to give permission. Wyost and Jubbonti were also approved with interchangeability designations.¹

“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 healthcare 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, commented.²

Global Prevalence of Indications and Clinical Data

Osteoporosis is a significant issue in Europe, causing 4.3 million fragility fractures each year and driving health care costs beyond €56 billion annually.⁴ Additionally, the CDC's National Center for Health Statistics reported that an estimated 10.2 million US adults 50 years or older had osteoporosis in 2010, with 43.3 million more having low bone mass.⁵

Regarding bone metastases, between 2010 and 2015, 85,296 out of 1.4 million patients newly diagnosed with solid malignancies had bone metastases, according to data from the Surveillance, Epidemiology, and End Results database.⁶ Lung, breast, and prostate cancers were the most likely to spread to bone. Lung cancer had the highest prevalence of bone metastases at diagnosis (18.05%), followed by liver (6.63%), nasopharynx (6.33%), and renal cancer (5.45%). Breast and prostate cancer had lower prevalence at diagnosis (3.66% and 4.61%, respectively), but they had the highest proportion of bone metastases among all distant metastases (64.20% and 59.89%, respectively).

The FDA and EMA approvals of SB16 were based on a comprehensive evaluation of analytical, nonclinical, and clinical data. A phase 1 randomized, double-blind study confirmed pharmacokinetic (PK) equivalence between SB16, EU-sourced reference denosumab, and US-sourced reference denosumab in healthy male participants, meeting primary PK end points.⁷

Additionally, a phase 3 randomized, double-blind, multicenter study in patients with postmenopausal osteoporosis demonstrated equivalent efficacy and comparable safety, immunogenicity, PK, and pharmacodynamics (PD) profiles between SB16 and reference denosumab.⁸ The primary end point—percent change in lumbar spine bone mineral density at month 12—was met, and follow-up to month 18 showed that switching to SB16 did not result in adverse changes in efficacy, PK, PD, safety, or immunogenicity.

References

1. Jeremais S. FDA approves first denosumab biosimilars. The Center for Biosimilars^®. March 5, 2024. Accessed February 17, 2025. https://www.centerforbiosimilars.com/view/fda-approves-first-denosumab-biosimilar

2. FDA approves Samsung Bioepis’ Ospomyv, Xbryk (denosumab-dssb), a biosimilar to Prolia and Xgeva. Press release. Samsung Bioepis; February 15, 2025. Accessed February 17, 2025. https://www.businesswire.com/news/home/20250215814020/en/FDA-Approves-Samsung-Bioepis-denosumab-dssb-a-Biosimilar-to-Prolia-and-Xgeva

3. Samsung Bioepis gains European Commission (EC) approval for denosumab biosimilar (Obodence, Xbryk). Press release. Samsung Bioepis; February 15, 2025. Accessed February 17, 2025. https://www.businesswire.com/news/home/20250215715912/en/Samsung-Bioepis-Gains-European-Commission-EC-Approval-for-Denosumab-Biosimilar

4. Scorecard for osteoporosis in Europe: scope 2021 summary report. International Osteoporosis Foundation. 2021. Accessed February 17, 2025. https://www.osteoporosis.foundation/scope-2021

5. Sarafrazi Z, Wambogo EA, Shepherd JA. Osteoporosis or low bone mass in older adults: United States, 2017–2018. National Center for Health Statistics. March 2021. NCHS Data Brief No 405. Accessed February 17, 2025. https://www.cdc.gov/nchs/products/databriefs/db405.htm#:~:text=Osteoporosis%20is%20the%20most%20common,United%20States%20in%202017%E2%80%932018

6. Zhang J, Cai D, Hong S. Prevalence and prognosis of bone metastases in common solid cancers at initial diagnosis: a population-based study. BMJ Open. 2023;13(10):e069908. doi: 10.1136/bmjopen-2022-069908

7. Lee HA, Kim S, Seo H, Kim S. A phase I, randomized, double-blind, single-dose pharmacokinetic study to evaluate the biosimilarity of SB16 (the proposed denosumab biosimilar) with reference denosumab in healthy male subjects. Expert Opin Investig Drugs. 2023;32(10):959-966. doi:10.1080/13543784.2023.2273510

8. Eastell R, Langdahl B, Chung Y-S, et al. A randomized, double-blind, phase III study to compare SB16 (proposed denosumab biosimilar) to reference denosumab in patients with postmenopausal osteoporosis: 18-month results. Presented at 2024 European Calcified Tissue Society (ECTS) Congress; May 25-28, 2024; Marseille, France.