Background SB5, a biosimilar to adalimumab reference product (ADL), 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 SB5 and EU sourced ADL (EU-ADL), SB5 and US sourced ADL (US-ADL), and between EU-ADL and US-ADL. Safety, tolerability, and immunogenicity were investigated as secondary objectives.
Methods This study was a randomised, single-blind, 3-arm, parallel group study in 189 healthy subjects. In each arm, all subjects received a single 40 mg dose of SB5, EU-ADL, or US-ADL by subcutaneous injection 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 adalimumab 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 SB5 and EU-ADL comparison, SB5 and US-ADL comparison, and EU-ADL and US-ADL 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 SB5, EU-ADL, and US-ADL groups. The most frequent TEAEs were nasopharyngitis and headache. The majority of TEAEs were mild to moderate in severity. Two serious adverse events (SAEs) were reported. Both SAEs were assessed not to be related to the study drugs. 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 SB5 and EU-ADL, SB5 and US-ADL, and between EU-ADL and US-ADL in healthy subjects. All three adalimumab products were generally well tolerated with similar safety profiles.
Disclosure of Interest D. Shin Employee of: Samsung Bioepis, Y. Kim Employee of: Samsung Bioepis, H. S. Kim Employee of: Samsung Bioepis, R. Fuhr Grant/research support from: Samsung Bioepis, T. Körnicke Grant/research support from: Samsung Bioepis