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

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.

A Randomized, Double-Blind, Single-Dose Study Comparing the Biosimilarity of HOT-1010 With Bevacizumab (Avastin®) in Chinese Healthy Male Subjects

“…The mean t 1/2 of HOT-1010 and Avastin ® was 14.6 d and 14.9 days, which was consistent with the results of other bevacizumab biosimilars (13.1-19.3 days) in Chinese, Indian, Caucasian and Korean healthy male subject studies (Knight et al, 2016;Zhang et al, 2018;Wang et al, 2019;Liu et al, 2020;Shin et al, 2020;Singh et al, 2020). The median T max of HOT-1010 (3.48 h) was similar to that of bevacizumab and other bevacizumab biosimilars (2.5-4.5 h) when intravenous dose ranged from 1 to 3 mg/kg (Zhang et al, 2018;Wang et al, 2019;Liu et al, 2020;Shin et al, 2020;Singh et al, 2020). HOT-1010 was well-tolerated and no safety concerns were identified, and safety profiles were similar between HOT-1010 group and Avastin ® group.…”

“…Although the exact mechanisms are not clear yet, these AEs of HOT-1010 should be paid more attention in the future study. Additionally, 82 subjects were found to be negative for ADA test, other studies also showed the relatively low immunogenicity of bevacizumab (Knight et al, 2016;Zhang et al, 2018;Wang et al, 2019;Liu et al, 2020;Shin et al, 2020;Singh et al, 2020), the comparison of immunogenicity still needs to be further investigated with larger sample size.…”

SB8: A Bevacizumab Biosimilar

“…Similarity between SB8 and EU-sourced reference bevacizumab was demonstrated as geometric LSM ratios and their 90% CIs for AUC ∞ , AUC last and C max (primary endpoints) were within the prespecified acceptance range of 0.80–1.25 in healthy volunteers [ 4 ]…”

“…Pharmacokinetic similarity of SB8 to EU-sourced bevacizumab was demonstrated in a randomized, double-blind, phase 1 pharmacokinetic study in healthy volunteers [ 4 ]. The 90% CI for geometric least squares means ratios for the primary endpoints of area under the concentration-time curve (AUC) from time zero to infinity, AUC from time zero to the last quantifiable concentration and the maximum observed serum concentrations (C max ) were within the prespecified bioequivalence margin of 80.00–125.00% [ 4 ]. Furthermore, in a phase 3 study in patients with NSCLC (Sect.…”

“…SB8 is approved in the EU for same types of cancer as bevacizumab (Table 2 ) [ 1 ]. SB8 has similar physicochemical, functional and pharmacodynamic characteristics to those of reference bevacizumab [ 2 , 3 ] and pharmacokinetic similarity of the agents has also been demonstrated [ 3 , 4 ]. This article summarizes, from an EU perspective, the key features of SB8 and its clinical use in the treatment of various cancers, focusing on non-small cell lung cancer (NSCLC).…”