Background SB2, a biosimilar to infliximab reference product (INF), has an identical amino acid sequence and similar physicochemical and in vitro functional properties to its reference drug.
Objectives The primary objective of this study was to demonstrate pharmacokinetic (PK) equivalence between SB2 and EU sourced INF (EU-INF), SB2 and US sourced INF (US-INF), and between EU-INF and US-INF. Safety, tolerability, and immunogenicity were investigated as secondary objectives.
Methods This study was a randomised, single-blind, 3-arm, parallel group study in 159 healthy subjects. In each arm, all subjects received a single 5 mg/kg dose of SB2, EU-INF, or US-INF by intravenous infusion on Day 1 and then were observed for 71 days during which the PK, safety, tolerability, and immunogenicity measurements were made. The serum concentration of infliximab was measured using an enzyme-linked immunosorbent assay (ELISA). The primary PK parameters were area under the concentration-time curve from time zero to infinity (AUCinf), area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast), and maximum concentration (Cmax). Equivalence for the primary PK parameters was to be concluded if the 90% confidence intervals (CIs) for the ratio of geometric least squares means (LSMeans) of the groups compared were completely contained within the pre-defined equivalence margin of 0.8 to 1.25 using an analysis of variance (ANOVA).
Results All of the 90% CIs for the geometric LSMeans ratios of primary PK parameters for SB2 and EU-INF comparison, SB2 and US-INF comparison, and EU-INF and US-INF comparison were within the pre-defined equivalence margin of 0.8 to 1.25 (Table). The proportion of subjects who experienced treatment-emergent adverse events (TEAEs) was comparable between the SB2, EU-INF, and US-INF groups. The most frequent TEAEs were nasopharyngitis and headache. The majority of TEAEs were mild to moderate in severity. Three serious adverse events (SAEs) were reported in two subjects from SB2 group where one SAE was assessed to be related to the study drug: one subject had a Borrelia infection which resolved without sequelae. There were no statistically significant differences in the incidence of post-dose anti-drug antibodies between the three groups.
Conclusions This study demonstrated PK equivalence between SB2 and EU-INF, SB2 and US-INF, and between EU-INF and US-INF in healthy subjects. All three infliximab products were generally well tolerated with similar safety profiles.
Disclosure of Interest D. Shin Employee of: Samsung Bioepis, Y. Kim Employee of: Samsung Bioepis, Y. S. Kim Employee of: Samsung Bioepis, R. Fuhr Grant/research support from: Samsung Bioepis, T. Körnicke Grant/research support from: Samsung Bioepis
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