Abstract
PurposeThis study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males.MethodsIn this randomized, single-blind, single-dose, three-arm, parallel-group study, healthy subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area under the serum concentration–time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (Cmax). Secondary endpoints included safety and immunogenicity.ResultsAUCinf and Cmax were similar across the three groups. Geometric means ratio (GMR) for Cmax and AUCinf, respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUCinf and Cmax were within the prespecified standard PK bioequivalence criteria of 0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When analyzed by investigational site, the incidence and severity of AEs were comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies was detected.ConclusionsThis study demonstrated the PK similarity of ABP 215 to both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to bevacizumab (EU). Safety and tolerability were comparable between treatments and no subject developed binding or neutralizing anti-drug anti-bodies.
Highlights
Bevacizumab is a recombinant humanized immunoglobulin G1 monoclonal anti-body that inhibits angiogenesis by binding to vascular endothelial growth factor (VEGF) and preventing its interaction with VEGF receptors on the surface of endothelial cells [1, 2]
The primary objective of this study was to demonstrate PK bioequivalence determined by comparing AUCinf and Cmax in subjects treated with ABP 215 to those treated with bevacizumab (US) and bevacizumab (EU)
A total of 191 (94.5%) subjects completed the study; 63 (92.6%) subjects in the ABP 215 treatment group, 64 (95.5%) subjects in the bevacizumab (US) group, and 64 (95.5%) subjects in the bevacizumab (EU) group
Summary
Bevacizumab is a recombinant humanized immunoglobulin G1 monoclonal anti-body that inhibits angiogenesis by binding to vascular endothelial growth factor (VEGF) and preventing its interaction with VEGF receptors on the surface of endothelial cells [1, 2]. Bevacizumab is approved for treatment of several types of cancer, including colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma, where it has been shown to improve progression-free and overall survival when used alone or in combination with other cancer therapies [3, 4]. Bevacizumab was approved by the US Food & Drug Administration (FDA) ( Avastin®; Genentech, Inc., San Francisco, USA) in 2004 and by the European Medicines Agency (EMA) (Avastin®; Roche Pharma AG, GrenzachWyhlen, Germany) in 2005 [3, 4]. Several proposed bevacizumab biosimilars are in development, some of which have completed or currently are in Phase III development [5,6,7,8]. ABP 215, a proposed bevacizumab biosimilar, was submitted for approval to the US FDA and EMA in 2016 [5, 9].
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