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

ABSTRACT:

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.

SUBMITTER: Wynne C 

PROVIDER: S-EPMC6138499 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature