Phase 1 Trial Provides Further Insight into Denosumab Biosimilar SB16

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Data from a single-dose study of healthy male adults is providing an overview of the pharmacokinetic and pharmacodynamic comparability of SB16, a denosumab biosimilar, relative to European Union- and United States-sourced denosumab.

A phase 1, parallel-group trial comparing a single 60 mg dose of SB 16 against groups receiving either European Union-sourced or United States-sourced denosumab, results of the study suggest the primary pharmacokinetic parameters were within the predefined equivalence margin, with the pharmacodynamic, safety, and immunogenicity profiles also comparable between the treatment groups.¹

“Treatment with a single dose of SB16 was generally safe and well-tolerated in healthy male subjects, and a safety profile in terms of incidence of treatment emergent adverse events were comparable with EU-DEN and US-DEN. The development of post-dose [anti-drug antibodies] to denosumab was also comparable between all treatment groups and no neutralizing antibodies were detected,” wrote investigators.¹

With denosumab serving as a staple in the management of osteoporosis, introduction of a biosimilar product could provide significant cost savings for individuals and health systems. Developed by Samsung Bioepis, SB16 has been the subject of multiple trials, including positive data from a phase 3 trial presented at the American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting. In addition to the phase 3 trial, providers were also given a glimpse into topline results from the current phase 1 trial at ASBMR 2023.²

A double-blind, parallel group, single-dose trial, the study randomized participants in a 1:1:1 ratio to 1:1:1 to receive a single 60 mg dose of either SB16, European Union-sourced denosumab, or United States-sourced denosumab subcutaneously, with assessments of pharmacokinetic equivalence, pharmacodynamics, safety, tolerability, and immunogenicity taking place over 197 days. For the purpose of analysis, blood samples for pharmacokinetics analysis were collected at predose, 12, 24, 48, 96, 144, 192, 240, 288, 336, 504, 672, 1008, 1344, 2016, 2688, 3360, 4032, and 4704 hours postdose.¹

Investigators evaluated pharmacokinetic equivalence using as area under the concentration-time curve (AUC) from time zero to infinity, AUC from time zero to the last quantifiable concentration, and maximum serum concentration (Cmax). Equivalence was determined if 90% confidence intervals (CIs) for the ratio of geometric least squares means (LSMeans) were within the equivalence margin of 0.80 to 1.25.¹

Conducted in 2 centers in the US and a single center in France, the trial required patients to be 28-55 years of age, a body weight of 60.0-95.0 kg, and a body mass index of 20.0-29.9 kg/m2 for inclusion. A total of 168 subjects were included in the study, with 56 included in each treatment group.¹

Upon analysis, results suggested all of the corresponding 90% CI of geometric LSMeans ratio of primary pharmacokinetic parameters were within the predefined equivalence margins. Additionally, further analysis indicated the pharmacodynamic, safety, and immunogenicity profiles were also comparable between the treatment groups.¹

Investigators pointed to multiple limitations within their study to consider when interpreting results. These included being limited to healthy male adults, which investigators pointed out was done because they are considered to be a more homogeneous and represent sensitive population to compare pharmacokinetic characteristics than patients with various disease-related factors and females with risk of reproductive toxicity and immunogenicity.¹

“Biosimilars, which have been clinically studied and have demonstrated to be bioequivalent in pharmacokinetics, and comparability in safety, efficacy, and immunogenicity, may be more cost-effective product of biologics which may help to increase patient access," investigators wrote.¹ "Our results support the demonstration of pharmacokinetic similarity between SB16 and reference DEN (EU-DEN and US-DEN). In addition, the comparability of pharmacodynamic, safety, and immunogenicity was also verified.”

References:

1. Lee H, Kim S, Seo H, Kim S. A phase I, randomized, Double-blind, single-dose pharmacokinetic study to evaluate the biosimilarity of SB16 (proposed denosumab biosimilar) with reference denosumab in healthy male subjects [published online ahead of print, 2023 Oct 23]. Expert Opin Investig Drugs. 2023;10.1080/13543784.2023.2273510. doi:10.1080/13543784.2023.2273510
2. Pine L. Denosumab biosimilar SB16 meets all primary endpoints in phase 1, 3 studies. HCP Live. October 16, 2023. Accessed October 24, 2023. https://www.hcplive.com/view/denosumab-biosimilar-sb16-meets-all-primary-endpoints-in-phase-1-3-studies.