Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab

Abstract

ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab.

Rapid characterization of structural and functional similarity for a candidate bevacizumab (Avastin) biosimilar using a multipronged mass‐spectrometry‐based approach

“…Covalent acetylation is also a possibility but lacks a plausible mechanism in the manufacturing and sample handling processes used and has not previously been observed for Avastin. Glycation has been proposed to occur in Avastin, however, we see no direct evidence for this phenomenon in the data (ie, it may account for some of the complexity in the peak distribution, but we cannot resolve individual peaks that would correspond to glycation). The next common glycosylation, G1F, involves the addition of a galactose to one of the N‐acetylglucosamine termini (Figure E).…”

Efficacy and Safety of the Biosimilar ABP 215 Compared with Bevacizumab in Patients with Advanced Nonsquamous Non–small Cell Lung Cancer (MAPLE): A Randomized, Double-blind, Phase III Study

“…Similarity between ABP 215 and bevacizumab has been demonstrated in multiple, rigorous nonclinical and preclinical evaluations. ABP 215 has been shown to have the same primary and higher-order structure as bevacizumab (3). In addition, high similarity between ABP 215 and bevacizumab has been demonstrated with respect to biological functions in molecular studies and pharmacokinetic parameters in healthy volunteers (3,4).…”

“…ABP 215 has been shown to have the same primary and higher-order structure as bevacizumab (3). In addition, high similarity between ABP 215 and bevacizumab has been demonstrated with respect to biological functions in molecular studies and pharmacokinetic parameters in healthy volunteers (3,4). Here, we report the results of a phase III randomized study (MAPLE; registered at ClinicalTrials.gov, NCT01966003) comparing the efficacy, safety, immunogenicity, and pharmacokinetic profiles of ABP 215 and bevacizumab reference product (RP) in patients with advanced nonsquamous NSCLC.…”

Physicochemical and functional assessments demonstrating analytical similarity between rituximab biosimilar HLX01 and the MabThera®

“…All spectra exhibit strong β-sheet bands at around 1639 cm −1 and 1689 cm −1 as well as a β-turn band at around 1670 cm −1 , indicating the presence of antiparallel β-sheet structure typically observed in antibodies. 19 When compared with the reference spectrum of RS201505020304-RM04, the similarity of all samples were greater than 0.99. Collectively, DSC, CD and FTIR results demonstrated that the higher order structures of HLX01 were highly similar to those of the RPs.…”