A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

Donghoon Shin, Yoon Jung Lee, Jihye Choi, Dahyoung Lee, Minjeong Park, Magdalena Petkova, Donghoon Shin, Yoon Jung Lee, Jihye Choi, Dahyoung Lee, Minjeong Park, Magdalena Petkova

Abstract

Purpose: To compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US).

Methods: In this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3 mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration-time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUClast), and maximum observed serum concentration (Cmax). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00-125.00%. Safety and immunogenicity were also investigated.

Results: The 90% CIs for the geometric LSMean ratios of AUCinf, AUClast and Cmax were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUCinf, 88.65%, 89.08% and 100.49% for AUClast and 99.59%, 101.15% and 101.56% for Cmax, respectively. Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8: 50.0%, bevacizumab-EU: 37.5%, bevacizumab-US: 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected.

Conclusion: This study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. CLINICALTRIALS.

Gov identifier: NCT02453672 (submitted date); EudraCT number: 2015-001,026-41.

Keywords: Bevacizumab; Biosimilar; Immunogenicity; Pharmacokinetics; SB8.

Conflict of interest statement

Dr. D. Shin reports personal fees from Samsung Bioepis Co., Ltd., during the conduct of the study; Dr. Y. J. Lee reports personal fees from Samsung Bioepis Co., Ltd., during the conduct of the study; Dr. J. Choi reports personal fees from Samsung Bioepis Co., Ltd., during the conduct of the study, Dr. D. Lee reports personal fees from Samsung Bioepis Co., Ltd., during the conduct of the study; Dr. M. Park reports personal fees from Samsung Bioepis Co., Ltd., during the conduct of the study and Dr. M. Petkova reportss personal fees from SGS LSS, during the conduct of the study. All the authors are employees of either Samsung Bioepis Co., Ltd. or of an organization contracted by Samsung Bioepis Co., Ltd. for the present study. There are no other relationships or activities that could appear to influence the submitted work.

Figures

Fig. 1
Fig. 1
CONSORT diagram of participants flow through the trial. Bevacizumab-EU European Union-sourced bevacizumab, Bevacizumab-US United States-sourced bevacizumab, PK pharmacokinetic. Included in PK population since the withdrawal was made between day 71 and day 85 (end of study), after PK blood sampling by day 71
Fig. 2
Fig. 2
Mean bevacizumab serum concentrations versus nominal times on linear and semi-logarithmic scale (PK population). Mean serum concentrations versus nominal times on linear (top graph) and semi-logarithmic scale (bottom graph) of SB8, bevacizumab-EU, and bevacizumab-US. Graphs were made with GraphPad Prism (GraphPad Software, La Jolla, CA, USA) version 8.4.1. Bevacizumab-EU: bevacizumab sourced from the European Union, Bevacizumab-US: bevacizumab sourced from the United States

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Source: PubMed

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