Bioequivalence confirmed in the first population PK analysis for a bevacizumab biosimilar based on a comparative clinical study in patients with cancer
Abstract published: August 2021
Bioequivalence of biosimilars with their reference biologic must be demonstrated by exhaustive clinical testing as mandated by regulatory authorities. As part of this process, this study assessed the comparability of a bevacizumab biosimilar versus its originator in terms of PK values using a validated computer software model.
Bevacizumab is a recombinant monoclonal antibody that inhibits angiogenesis – the formation of new blood vessels necessary for tumor growth and survival – and used in the treatment of several cancers, including non-small cell lung cancer (NSCLC). Following the release of bevacizumab originator product, PF-06439535 (ZibarevTM) is a bevacizumab biosimilar that has undergone an extensive development program of analytical, preclinical, and clinical studies.
In clinical use, bevacizumab is dosed according to body weight and intravenously infused at a constant rate. Thereafter, this antibody drug is distributed systemically to body compartments, exerts its therapeutic effects, and is eliminated metabolically by enzymatic breakdown and excretion. These processes are represented by two pharmacokinetic (PK) parameters, the drug clearance (CL) and volume of distribution (V1), which, for two biosimilar drugs, should have the same values.
Potential differences in PK between bevacizumab biosimilar and reference bevacizumab emerging from a comprehensive comparator study were investigated using a population modeling approach. In this randomized clinical trial, patients with NSCLC were treated with either PF-06439535 or bevacizumab sourced from the European Union (bevacizumab-EU), both with four to six cycles of concomitant chemotherapy, and followed for 1 year. Before and after each cycle, serum samples were collected for analysis of bevacizumab (PF-06439535 or bevacizumab-EU) concentrations by ELISA. The data were pooled and analyzed by validated population PK model using customized computer software.
In general, the model successfully reproduced the observed longitudinal bevacizumab concentration–time profiles for the entire patient pool. The model confirmed there were no appreciable differences in CL and V1 between PF-06439535 and bevacizumab-EU in patients with NSCLC. These findings provide additional support for the demonstration of PK similarity between biosimilar PF-06439535 and reference bevacizumab.
The bevacizumab biosimilar, PF-06439535, demonstrated no clinical differences in either drug clearance or volume of distribution when compared with the reference product.