Background SB4, a biosimilar to etanercept reference product (ETN), has an identical amino acid sequence, 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 SB4 and EU sourced ETN (EU-ETN), between SB4 and US sourced ETN (US-ETN), and between EU-ETN and US-ETN. Safety, tolerability, and immunogenicity were investigated as secondary objectives.
Methods This study was a randomised, single-blind, three-part (Part A, Part B and Part C), 2-treatment, 2-period cross-over study in 138 healthy male subjects. In each part, 46 subjects were randomised in a 1:1 manner to receive a single 50 mg subcutaneous dose of SB4 or the reference drug (Part A: SB4 or EU-ETN, Part B: SB4 or US-ETN, Part C: EU-ETN or US-ETN) in Period 1 followed by the cross-over treatment in Period 2 according to their assigned treatment sequence. Study treatments were separated by a 28 day washout period. PK assessment was performed 21 days after the treatment in each period. Immunogenicity was assessed at pre-dose and 28 days after the first treatment in Period 1.
The primary PK parameters were area under the concentration-time curve from time zero to infinity (AUCinf) and maximum concentration (Cmax). Equivalence for the primary PK parameters was to be concluded if the 90% confidence interval (CI) of 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 The geometric LSMeans ratio of AUCinf and Cmax were 0.990 and 1.037 (Part A), 1.011 and 1.044 (Part B), and 1.005 and 1.033 (Part C), respectively. All 90% CIs for the primary PK parameter comparisons in Part A, B, and C were completely contained within the pre-defined equivalence margin (Table).
The proportion of subjects who experienced treatment-emergent adverse events (TEAEs) was comparable between SB4 and EU-ETN (39.1% vs. 34.8%), SB4 and US-ETN (50.0% vs. 43.5%), and between EU-ETN and US-ETN (37.0% vs. 30.4%) in each part. The most frequent TEAEs reported were nasopharyngitis, headache, and injection site reaction. The majority of TEAEs reported was mild or moderate in severity and transient. There were no serious adverse events (SAEs) or deaths reported during the study.
Conclusions This study demonstrated PK equivalence of SB4 to EU-ETN, of SB4 to US-ETN, and of EU-ETN to US-ETN in healthy male subjects. All three etanercept products were generally well tolerated with similar safety profiles.
Disclosure of Interest Y. J. Lee Employee of: Samsung Bioepis, D. Shin Employee of: Samsung Bioepis, Y. Kim Employee of: Samsung Bioepis, J. W. Kang Employee of: Samsung Bioepis, R. Fuhr Grant/research support from: Samsung Bioepis, A. Gauliard Grant/research support from: Samsung Bioepis