Bioavailability, safety and immunogenicity of biosimilar infliximab (BOW015) compared to reference infliximab.

OBJECTIVES: To compare the single-dose pharmacokinetics (PK), safety, and immunogenicity of the biosimilar infliximab (BOW015) to reference infliximab (rIFX) in healthy volunteers and to establish bioequivalence. METHODS: In this randomized, double-blind, parallel-group, single-dose study, subjects received either BOW015 or rIFX. Both drugs were administered as a single IV 5 mg/kg dose over 2 hours on day 1. PK sampling occurred 10 times over 3 days and during safety and immunogenicity follow-up on day 4 and 1, 2, 3, 5, 7, 9, and 12 weeks after the infusion. RESULTS: Of the 84 healthy male Caucasian subjects randomized, 43 received BOW015 and 41 received rIFX. PK parameters (geometric mean) for BOW015 vs. rIFX were as follows; C(max) 142.47 vs. 126.74 μg/mL, AUC(0-t) 36,211 vs. 34,304 h×μg/mL, and AUC(0-inf) 36,775 vs. 34,801 h×μg/mL. The point estimates of the BOW015/rIFX geometric mean ratios (90% CI) were; C(max) 1.13 (1.07 - 1.18), AUC(0-t) 1.06 (0.98 - 1.14), and AUC(0-inf) 1.06 (0.98 - 1.15). Overall, anti-drug antibodies were detected in 18.6% of BOW015-treated subjects and 24.4% of rIFX-treated subjects. A total of 26 (60.5%) subjects in the BOW015 group reported 50 treatment-emergent adverse events (TEAEs) and 27 (65.9%) subjects in the rIFX group reported 54 TEAEs. CONCLUSIONS: Bioequivalence of BOW015 to rIFX is demonstrated as 90% CIs for the study drug mean ratios of C(max), AUC(0-t), and AUC(0-inf) were within the log-transformed ± 20% equivalence range of 0.80 - 1.25. Safety and immunogenicity were also comparable.