FDA-Approved SB16 Biosimilar Demonstrates Equivalence to Prolia

For countless women navigating postmenopausal osteoporosis (PMO), effective treatment often comes with a hefty price tag.1 New research shows that denosumab biosimilar SB16 is equivalent to the reference product, Prolia (denosumab), up to 12 months, which carries substantial implications for expanding access to effective PMO treatment, particularly for those facing financial barriers to originator denosumab therapy.2

PMO is a highly prevalent chronic bone disease affecting approximately 20% of women 50 years and older in the US, characterized by decreased bone mass and an increased risk of fragility fractures. Denosumab, a human monoclonal antibody, works by inhibiting osteoclast activity, leading to increased bone density. However, as an originator biologic, its cost can be prohibitive for many patients. Biosimilars, which are highly similar to already approved biologics in terms of quality, efficacy, and safety, offer a crucial alternative, often at a lower cost.

In February 2025, the FDA approved SB16 as denosumab-dssb, which will be marketed as Ospomyv and Xbryk depending on the indication.3 Denosumab-dssb is also approved in the European Union as Obodence or Xbryk. However, they are unable to enter the market until Samsung Bioepis settles its patent infringement case with reference manufacturer Amgen.4

The present multinational, double-blind, randomized phase 3 study, conducted across 40 sites in 5 countries (Czech Republic, Denmark, Lithuania, Poland, and Republic of Korea) enrolled 457 postmenopausal women aged 55 to 80 years with a bone mineral density (BMD) T-score of the lumbar spine or total hip between –2.5 and –4.0. These participants were treatment-naive to biologic medicines for osteoporosis. The study's primary objective was to evaluate the biosimilarity of SB16 to denosumab in terms of efficacy, safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity.

A key finding of the study was the equivalence of SB16 to denosumab in the primary efficacy end point: the percent change from baseline in lumbar spine BMD at month 12. In the full analysis set, the least-squares mean percent change from baseline in lumbar spine BMD was 5.63% for the SB16 group and 5.30% for the denosumab group, with a treatment difference of 0.33% (90% CI, –0.25% to 0.91%). This fell well within the predefined equivalence margin of –1.45% to 1.45%, demonstrating statistically significant equivalence. Similar results were observed in the per-protocol set.

Beyond the primary end point, secondary efficacy measures consistently supported the equivalence. For instance, mean percent changes from baseline in total hip BMD at month 12 were 3.50% for SB16 and 3.25% for denosumab. Femoral neck BMD also showed comparable increases, with 2.79% for SB16 and 2.30% for denosumab at month 12.

The PD profiles, assessed through bone turnover markers such as serum CTX and P1NP, were also remarkably similar between the 2 groups, indicating comparable effects on bone resorption and formation. At month 12, the median percent change from baseline in serum CTX concentrations was 69.0% for SB16 and 69.6% for denosumab. PK analyses further confirmed comparable drug concentrations between SB16 and denosumab throughout the study period.

In terms of safety, SB16 exhibited a profile consistent with that of denosumab. Overall, 70.7% of patients in the SB16 group experienced at least 1 treatment-emergent adverse event compared with 71.0% in the reference denosumab group. The incidence of serious AEs (SAEs) was comparable (3.6% for SB16 vs 3.5% for denosumab). The most frequently reported AE of special interest was hypocalcemia, occurring in 9.8% of the SB16 group and 11.7% of the reference denosumab group, with most cases being mild and asymptomatic.

Importantly, no cases of osteonecrosis of the jaw or atypical femoral fractures were reported in either group during the main study period. Immunogenicity was low and comparable, with fewer than 1% of patients in both groups testing positive for antidrug antibodies.

This robust clinical evidence demonstrating the biosimilarity of SB16 to denosumab is a critical step toward increasing treatment accessibility for patients with PMO. The high cost of originator denosumab has historically posed a significant barrier to consistent therapy, potentially leading to suboptimal bone health management and increased fracture risk.

“Because this study was initiated and designed to assess equivalence of a biosimilar to its reference product, a larger sample size to determine long-term fracture risk was not considered, which could be a potential limitation of this study,” the authors wrote.

References

1. Paying for Prolia. Amgen. Updated January 8, 2025. Accessed June 2, 2025. https://www.prolia.com/paying-for-prolia

2. Langdahl B, Chung Y-S, Plebanski R, et al. Proposed denosumab biosimilar SB16 vs reference denosumab in postmenopausal osteoporosis: phase 3 results up to month 12. J Clin Endocrinol Metab. 2025;110(6):e1951-e1958. doi:10.1210/clinem/dgae611

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

4. Wong HK, Menon AB. Biosimilar cases to watch: Prolia/Xgeva and denosumab competitors. The Center for Biosimilars. March 11, 2025. Accessed June 2, 2025. https://www.centerforbiosimilars.com/view/biosimilar-cases-to-watch-prolia-xgeva-and-denosumab-competitors