A randomized phase I comparative pharmacokinetic study comparing SB5 with reference adalimumab in healthy volunteers

Abstract

SummaryWhat is known and objective: SB5 is a biosimilar to the reference adalimumab (ADL) currently in development. The primary study objective was to demonstrate pharmacokinetic (PK) equivalence of SB5 to European Union-sourced adalimumab (EU-ADL), and United States-sourced adalimumab (US-ADL) in healthy subjects. Safety, tolerability and immunogenicity were also assessed as secondary objectives. Methods:In this phase I, single-blind trial, 189 healthy volunteers were randomized to a single 40 mg dose of SB5, EU-ADL or US-ADL and PK was evaluated for 71 days afterwards. Serum adalimumab concentrations were measured using an enzymelinked immunosorbent assay (ELISA) test. PK parameters were calculated based on actual sampling times relative to dosing and non-compartmental analysis methods, and equivalence was determined using predefined margins of 0.8-1.25.Results and discussion: Baseline characteristics and demographics were comparable between the three groups. Mean values of area under the concentration-time curve from time zero to infinity (AUC inf ), maximum serum concentration (C max ) and AUC from time zero to the last quantifiable concentration (AUC last ) were similar between groups, and 90% confidence interval for these parameters were within the predefined equivalence margins for all pairwise comparisons. No discontinuations due to treatment-emergent adverse events (TEAEs) or deaths were reported.Number and kind of TEAEs were comparable between the three groups and considered mild to moderate. The incidence of subjects with antidrug antibodies (ADA) and the overall incidence of neutralizing antibody (NAb) were comparable across the three groups.What is new and conclusion: The PK of SB5 was equivalent to that of EU-ADL and US-ADL. SB5 was well tolerated with similar safety and immunogenicity profile to EU-ADL and US-ADL. K E Y W O R D S bioequivalence, biosimilar, clinical pharmacokineticsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Switching From Reference Adalimumab to SB5 (Adalimumab Biosimilar) in Patients With Rheumatoid Arthritis

“…The European Commission granted a marketing authorization for SB5 in August 2017. Pharmacokinetic (PK) equivalence and comparable safety for SB5 and ADA were demonstrated in a phase I study in healthy individuals . In a phase III randomized study in patients with moderate‐to‐severe RA, equivalent efficacy was demonstrated for SB5 and ADA, as seen in percentages of patients meeting the ACR 20% improvement criteria (achieving an ACR20 response) (72.4% and 72.2%, respectively) and additional efficacy end points up to 24 weeks; SB5 was well tolerated, with PK, safety, and immunogenicity profiles comparable to those of ADA .…”

“…ADA is a recombinant human IgG1 specific for TNF that is approved for the treatment of RA as well as several other inflammatory conditions . SB5 (Imraldi; Samsung Bioepis) was developed as an ADA biosimilar and has an identical amino acid sequence and physicochemical and in vitro functional properties similar to those of reference ADA . The European Commission granted a marketing authorization for SB5 in August 2017.…”

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

“…To our knowledge, no published clinical trials evaluating the approved adalimumab biosimilars ABP 501, BI 695501, or SB5 in IBD, or real-world evidence for other infliximab biosimilars exist. All three adalimumab biosimilars have demonstrated pharmacokinetic similarity to the RP in equivalence studies in healthy subjects [125][126][127] and similar efficacy and safety in clinical trials in patients with RA [128][129][130].…”

Evaluation of similar quality attribute characteristics in SB5 and reference product of adalimumab

“…Although SB5 has slightly different non-glycosylated heavy chain (NGHC) levels compared to the reference product, the difference had no significant clinical impact. 19,20 Charge heterogeneity…”