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

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 (R)). 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 drugrelated 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.