A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin ® (EU and US) in healthy male subjects

Aim The aim of this study was to compare the pharmacokinetics (PK) of DRL_BZ with that of EU‐approved (reference medicinal product; RMP) and US‐licensed (reference product; RP) bevacizumab (Avastin ® ) in healthy male subjects. Methods In this double‐blind, parallel‐group, Phase 1 study (BZ‐01‐001), men aged 20–45 years were randomized 1:1:1 to receive a single intravenous infusion of 1 mg kg −1 of bevacizumab as DRL_BZ, RMP or RP. A total of 149 subjects were randomized (DRL_BZ, 50; RMP, 50; RP, 49). Primary endpoints included maximum observed serum concentration ( C max ), area under the concentration–time curve from time zero (pre‐dose) extrapolated to infinity (AUC (0–∞) ), and area under the concentration–time curve from time zero (pre‐dose) to last quantifiable concentration (AUC (0– t ) ). Secondary objectives were to compare the safety and immunogenicity of DRL_BZ with those of the reference products. Results Primary PK parameters were comparable across groups, and 90% confidence intervals for the geometric mean ratios of the primary PK endpoints were within the pre‐specified equivalence margins (80–125%) for all pairwise comparisons (DRL_BZ vs . RMP, DRL_BZ vs . RP and RMP vs . RP). No deaths or serious adverse events were reported. Similar numbers of subjects reported similar numbers of treatment‐emergent adverse events in the three treatment groups. One subject who received DRL_BZ had anti‐drug antibodies at the Day 85 visit; however, no anti‐drug antibodies were detected in this subject at the 12‐month follow‐up visit. Conclusions PK, safety and immunogenicity of DRL_BZ were comparable to EU‐approved and US‐licensed bevacizumab in healthy male subjects.