A phase 1 study comparing the proposed biosimilar BS-503a with bevacizumab in healthy male volunteers.

Abstract

This is a randomized, double‐blind, single‐dose, parallel group phase 1 study to assess pharmacokinetic similarity, safety, and tolerability of BS‐503a, a proposed bevacizumab biosimilar. A total of 114 male healthy subjects were randomized (1:1) to receive a single 3 mg/kg intravenous dose of either BS‐503a or bevacizumab (Avastin®). Pharmacokinetic (PK) blood samples were collected up to Day 78, and serum drug concentrations were measured using a validated enzyme‐linked immunosorbent assay. Pharmacokinetic similarity was evaluated using area under the serum concentration‐time curve from zero to infinity (AUC inf) as a primary PK parameter, and maximum serum concentration (C max) and area under the serum concentration‐time curve from zero to the last measurable time (AUC last) as secondary PK parameters. The 90% confidence intervals (CIs) of geometric mean ratio of AUC inf ranged 0.980–1.105, which met the predefined criteria of 0.80–1.25. The 90% CIs of geometric mean ratios for C max and AUC last were 1.009–1.125 and 0.982–1.096, respectively, falling into the same criteria. At least one drug‐related treatment emergent adverse event occurred in 18 and 21 subjects treated with BS‐503a and bevacizumab, respectively. The most common adverse events were headache, epistaxis, and rhinorrhea. Most adverse events were mild or moderate; however, one drug‐related serious adverse event of duodenal ulcer perforation was reported by a subject 47 days after treatment of BS‐503a. In conclusion, BS‐503a was demonstrated to have highly similar PK to bevacizumab and adverse events observed were consistent with those observed for bevacizumab.