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Phase I study comparing SB8 with reference bevacizumab Posted 08/01/2021

SB8, developed by Samsung Bioepis, was approved as a biosimilar of the reference product Avastin (bevacizumab) by the European Commission in August 2020 with the brand name of Aybintio [1]. The objective of this phase I study was to compare the pharmacokinetics, safety, tolerability and immunogenicity between SB8 and the European Union (EU) and United States (US) reference products (bevacizumab-EU and bevacizumab-US).

In this randomized, double-blind, single-dose, three-arm, parallel-group study, healthy male 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 (AUC∞) and to the last quantifiable concentration (AUClast), and maximum observed serum concentration (Cmax). Bioequivalence was achieved if the 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of the primary endpoints were within the pre-defined bioequivalence margins of 80.00%‒125.00%. Safety and immunogenicity were also investigated [2].

A total of 119 male participants received a single dose of study drug (SB8, n = 40; bevacizumab-EU, n = 40; bevacizumab-US, n = 39) and the final per-protocol population used in the pharmacokinetic (PK) analysis consisted of 114 participants (SB8, n = 38; bevacizumab-EU, n = 38; bevacizumab-US, n = 38). The 90% CIs of the geometric LSMeans ratios for AUC∞, AUClast, and Cmax were fully contained within the pre-defined bioequivalence margin of 80.00%‒125.00% for all comparisons between treatment groups. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUC∞, 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 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.

In summary, this phase I study demonstrated PK bioequivalence and comparable safety and immunogenicity profiles of SB8 to both reference products, bevacizumab EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. These results represent an important contribution to the totality of evidence supporting the biosimilarity of SB8 to its reference product bevacizumab, following the demonstration of analytical and functional similarity in extensive quality and non-clinical assessments. This totality of evidence is complemented by further clinical data from a phase III study [3] in patients with non-small-cell lung carcinoma, demonstrating equivalence of SB8 and bevacizumab in terms of best overall response rate and comparable safety, PK and immunogenicity.

Conflict of interest
The authors of the research paper [2] reported conflict of interest, including having received personal fees from or being employees of Samsung Bioepis. For full details of the authors’ conflict of interest, see the research paper [1].

Abstracted by Donghoon Shin, Medical Affairs, Samsung Bioepis, Incheon, Korea.

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References
1. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 8]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe 
2. Shin D, Lee YJ, Choi J, et al. A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers. Cancer Chemother Pharmacol. 2020;86(4):567-75.
3. Reck M, Luft A, Bondarenko I, et al. A phase III, randomized, double-blind, multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer. Lung Cancer. 2020;146:12 8.

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