A randomized, single-blind, single-dose study to assess the pharmacokinetic equivalence of the biosimilar ABP 215 and bevacizumab in healthy Japanese male subjects.

Purpose: Analytic, pharmacokinetic (PK), and clinical similarity between the biosimilar ABP 215 and bevacizumab has previously been demonstrated in global studies. Here we present a phase 1 study in healthy adult Japanese men.

Methods: This study was a randomized, single-blind, single-dose, parallel-group study comparing PK parameters of ABP 215 versus EU-authorized bevacizumab in healthy Japanese men. Primary endpoints were maximum observed serum concentration (C) and area under the serum concentration-time curve from time 0 to infinity (AUC). Secondary endpoints included AUC from time 0 to time of last quantifiable concentration (AUC), safety, tolerability, and immunogenicity.

Results: Baseline characteristics were similar among study subjects (n = 24/group). After a 3-mg/kg intravenous infusion, the geometric means (GMs) of C AUC, and AUC were 71.2 µg/mL, 25,259 µg h/mL, and 22,499.3 µg h/mL, respectively, for ABP 215 and 70.16 µg/mL, 25,801 µg h/mL, and 22,604.6 µg h/mL, respectively, for bevacizumab. The GM ratios (90% confidence interval; CI) for C AUC, and AUC were 1.015 (0.946-1.088), 0.979 (0.914-1.049), and 0.995 (0.941-1.053) for ABP 215 versus bevacizumab. All CIs fell within the prespecified bioequivalence margin (0.80-1.25). Adverse events (AEs) occurred in 2/24 subjects receiving ABP 215 and 1/24 receiving bevacizumab. There were no deaths or AEs leading to study discontinuation; no subject was positive for binding anti-drug antibodies (ADAs).

Conclusions: ABP 215 and bevacizumab showed PK similarity in Japanese men. Safety profiles were comparable between the two groups. The pharmacokinetics in Japanese subjects were consistent with those in a previous global PK equivalence study.