Pharmacokinetics of pertuzumab biosimilar compared with the original drug in cynomolgus monkeys

BACKGROUND: Developing biosimilar monoclonal antibodies for treating malignant diseases is a critical task. RPH-051 (pertuzumab) is a biosimilar drug, a recombinant humanized monoclonal antibody targeting type 2 human epidermal growth factor receptors. At the stage of non-clinical development, studies of pharmacokinetics of biosimilar vs. original drug product in a relevant animal species, provide important information on the comparability of drugs. AIM: To evaluate the pharmacokinetics of the biosimilar product RPH-051 in comparison with the original drug after a single intravenous injection in a cynomolgus monkey model. MATERIALS AND METHODS: The study was conducted in 8 cynomolgus monkeys (Macaca fascicularis) divided into 2 groups, each including 2 females and 2 males. The first group received the biosimilar RPH-051 (international nonproprietary name is pertuzumab, AO R-Pharm, Russia), the second group was treated with the comparator Perjeta® (international nonproprietary name is pertuzumab). The drugs were administered as a single intravenous dose of 50 mg/kg. Blood samples were collected before dosing, then at 1 min, 1, 2, 4, 8, 24 h, and on days 3, 7, 10, 14, 21 and 28 post-dosing. Quantitative analysis of pertuzumab serum levels was performed using enzyme-linked immunosorbent assay (ELISA) with spectrophotometric detection in the visible range of the spectrum. RESULTS: The method of quantitative assessment of serum level of pertuzumab using (ELISA) in cynomolgus monkeys was developed. The method was validated against the following parameters: selectivity, minimum required dilution, lower limit of quantification, calibration range, accuracy and precision (within the analytical run and between runs), specificity, linearity (possibility) of sample dilution, parallelism, and stability of the analyte in serum. Comparability of the drugs in the main pharmacokinetic parameters was established. The mean Cmax and AUClast values of RPH-051 and of the comparator were 1684.34 and 1405.34 μg/mL (Cmax); 265,282.18 and 280,168.92 (μg/mL)×h (AUClast), respectively. CONCLUSION: Comparability between the pharmacokinetic profiles of the biosimilar RPH-051 and the originator’s drug was demonstrated. In the course of the study, no adverse clinical events, animal body weight changes, or injection site reactions associated with the tested drugs were observed.