A randomized, single-dose, pharmacokinetic equivalence study comparing MB02 (proposed biosimilar) and reference bevacizumab in healthy Japanese male volunteers

Abstract

Purpose: MB02 is a biosimilar to bevacizumab that has demonstrated similar physicochemical and functional properties in in vitro studies to the reference bevacizumab (Avastin^®). This study aims to assess the pharmacokinetic (PK) similarity of MB02 to the reference bevacizumab in Japanese population.

Methods: This double-blind, randomized, parallel-group, single-dose PK study, was performed in healthy Japanese male volunteers. Subjects were equally randomized (1:1) to receive a single (3 mg/kg) IV dose of MB02 or reference bevacizumab. PK assessments were done up to 70 days post-dose. Non-compartmental parameters were calculated. PK similarity was determined using predefined equivalence range (0.80-1.25) for the area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC_0-∞). Immunogenicity samples were taken pre-dose and up to day 70. Safety was assessed throughout the study.

Results: In total, 48 subjects (24 in each treatment group) were dosed. Consequently to the observed similar PK profile, the 90% confidence interval for the geometric means ratio for the primary PK endpoint, AUC_0-∞, was within the predefined equivalence range (0.981-1.11). Forty-seven treatment-emergent adverse events (TEAEs) were reported in 20 subjects (41.7%) with comparable incidence among MB02 and reference bevacizumab groups (22 and 25, respectively), none of them was severe or serious. Anti-drug antibodies incidence was low and similar between treatment groups.

Conclusions: Pharmacokinetic similarity of MB02 to reference bevacizumab was evidenced in Japanese healthy subjects, with comparable safety and immunogenicity profile between treatments. This study supports the biosimilarity of MB02 to reference bevacizumab in Japanese population. ClinicalTrials.gov identifier: NCT04238650.

Keywords: Bevacizumab; Biosimilars; Japanese; MB02; Pharmacokinetics; Safety.

Fig. 1

Study participants flow

Fig. 2

Arithmetic mean serum concentration–time profiles of bevacizumab following single IV doses of MB02 and reference bevacizumab to healthy Japanese male subjects (up to 14 days and across All days). Pharmacokinetic population [Linear (A) and Semi-Logarithmic (B) Scale]