Denosumab Biosimilar SB16 Demonstrates Bioequivalence up to 18 Months

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The proposed denosumab biosimilar, SB16, demonstrated pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence, as well as equivalent efficacy, safety, and immunogenicity compared with the reference product among a cohort of postmenopausal women with osteoporosis for up to 18 months of treatment, according to recent research presented at the 2024 European Congress of Rheumatology (EULAR).¹

Denosumab, a US Food and Drug Administration (FDA)-approved medication, is indicated to treat postmenopausal women at high risk for fracture, patients with intolerance or inadequate response to other osteoporosis treatments, and patients who will be taking corticosteroids for ≥6 months and are at a high risk for fracture. The drug is also used to increase bone mass in men with osteoporosis at a high risk for fracture and men at a high risk for fracture treated with certain medications for prostate cancer.²

Previous trials have evaluated the biosimilarity of the proposed drug, a monoclonal antibody targeting RANK ligand (RANKL), for up to 12 months. The first trial was double-blind, 3-arm, multicenter, parallel group and single-dose study evaluating the pharmacokinetic equivalence between the biosimilar, Europe-sourced denosumab (EU-DEN), and United States-sourced denosumab (US-DEN).³

Investigators total of 168 healthy male participants aged between 28 – 55 years were enrolled in the study. Patients were randomized 1:1:1 to receive a single 60 mg subcutaneous dose of SB16, EU-DEN, or US-DEN. All corresponding 90% confidence intervals (CIs) of the geometric least squares means ratio of pharmacokinetic parameters between the 3 drugs were within the equivalence margin of .80 – 1.25.³

In the first part of a phase 3 trial, 457 patients were randomized 1:1 to subcutaneously receive either 60 mg of SB16 or the reference product at month 0, month 6, and month 12. The primary endpoints were the percent change from baseline in lumbar spine bone mineral density at 12 months. Other efficacy, safety, immunogenicity, and pharmacokinetic endpoints were also evaluated.³

The study met its primary endpoints and patients in the reference cohort were re-randomized 1:1 to begin SB16 or continue with denosumab.³

Among the initial cohort of patients, 407 were re-randomized into the SB16 + SB16 group (n = 206), DEN + DEN group (n = 101), or DEN + SB16 group (n = 100), of which 404 completed the switching period.¹

The mean percentage change from baseline in lumbar spine bone mineral density (BMD) was comparable between treatment groups at 18 months. In the SB16 + SB16 group, the least squares mean (LSM) of percentage change from baseline in lumbar spine BMD was 6.77 (standard error: 0.286).¹

The LSM difference in the full analysis set was –0.03% (90% confidence interval [CI] [–0.85, 0.79]) between SB16+SB16 and DEN+DEN groups and –0.52 (90% CI [–1.48, 0.43]) between the DEN+SB16 and DEN+DEN cohorts. The mean percentage change from baseline in total hip and femoral neck BMD at the end of the treatment period were comparable across treatment arms. Additionally, PK, PD, immunogenicity, and safety were similar among groups at the end of the study period.¹

“As we continue to advance with our biosimilar development, our endeavors to enhance understanding of biosimilars among healthcare professionals will continue through our scientific research, publication and educational activities,” Ilsun Hong, vice president and product evaluation team leader at Samsung Bioepis, said in a previous statement regarding the results of the phase 1 and 3 trials.³

Reference

1. ^{Eastell R, Langdahl B, Chung YS, Plebanki R, 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: EULAR. Vienna, Austria. June 12 – 15, 2024.}
2. ^{Prolia® (denosumab): Other approved indications. Prolia.com. (n.d.). https://www.prolia.com/proven-prolia-results/other-approved-indications}
3. ^{BioSpace. (2023, October 15). Samsung Bioepis presents phase 1 and 3 clinical results for SB16, a proposed biosimilar to Proliai (denosumab), at ASBMR 2023. https://www.biospace.com/article/releases/samsung-bioepis-presents-phase-1-and-3-clinical-results-for-sb16-a-proposed-biosimilar-to-prolia%E2%81%B1-denosumab-at-asbmr-2023/}