title: 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 (AUCinf) as a primary PK parameter, and maximum serum concentration (Cmax) and area under the serum concentration-time curve from zero to the last measurable time (AUClast) as secondary PK parameters. The 90% confidence intervals (CIs) of geometric mean ratio of AUCinfranged 0.980-1.105, which met the predefined criteria of 0.80-1.25. The 90% CIs of geometric mean ratios forCmaxand AUClastwere 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.
authors.affiliation: Daiichi Sankyo Co., Ltd. 1-2-58 Hiromachi Shinagawa-ku Tokyo 140-8710 Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tajima
authors.affiliation: Daiichi Sankyo Development Ltd. Chiltern Place, Chalfont Park Gerrards Cross SL9 0BG United Kingdom.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martinez
authors.affiliation: Daiichi Sankyo Co., Ltd. 1-2-58 Hiromachi Shinagawa-ku Tokyo 140-8710 Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Kobayashi
authors.affiliation: Daiichi Sankyo Pharma Development 399 Thornall Street Edison New Jersey 08837.
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.affiliation: Daiichi Sankyo Development Ltd. Chiltern Place, Chalfont Park Gerrards Cross SL9 0BG United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Dewland
keywords: BS‐503a; bevacizumab; biosimilar; healthy male volunteers; pharmacokinetics; safety; similarity