Review of Adalimumab Biosimilar SB5 in Immune-Mediated Inflammatory Diseases

Abstract

SB5 is an approved biosimilar of adalimumab, a recombinant monoclonal anti-tumor necrosis factor (TNF) antibody. The approval of SB5 was based on the comparison with reference adalimumab in analytical studies, pharmacokinetic (PK) and immunogenicity assessments, and randomized controlled trials. Efficacy data was primarily obtained in patients with rheumatoid arthritis, and extended to include additional indications such as psoriasis, Crohn's disease, or ulcerative colitis by extrapolation. Following its approval, additional post-marketing data have been collected comparing SB5 with reference adalimumab. This review summarizes the clinical data on SB5 from randomized controlled trials and provides a comprehensive overview of the available post-approval data. In "real-world" settings, SB5 was as effective as its reference product across different indications and countries, treatment persistence was well maintained throughout studies, and no new safety concerns were identified. In both controlled and "real-world" settings, switching from reference adalimumab to SB5 was not associated with altered efficacy or clinical complications. In post-approval studies, the quality of SB5 was consistent over time, independent of the batch and process changes, and the SB5 autoinjector was preferred over other autoinjectors by both healthcare professionals and patients. Taken together, these data support the use of SB5 whenever reference adalimumab is appropriate and demonstrate that switching from reference adalimumab to SB5 is feasible.

Keywords: Adalimumab; Anti-TNF; Biosimilar; Crohn’s disease; Inflammatory bowel disease; Psoriasis; Rheumatoid arthritis; SB5; Ulcerative colitis.

Fig. 1

Study design of the SB5 phase IV interchangeability study. ADL, reference adalimumab; EOS, end of study; F/U, follow-up; PASI50, 50% reduction in the Psoriasis Area and Severity Index; PK, pharmacokinetics

Fig. 2

Trend of biologic activities of Herceptin®. a Relative FcγRIIIa binding activity of Herceptin® (n = 98); b relative ADCC activity of Herceptin® (n = 102). Dotted line shows the min–max range of expiry date before August 2018, 1st drift and 2nd drift periods. Boxplot shows the interquartile range, median and outlier (◊). Statistical significance was assessed with one-way ANOVA (*P ≤ 0.05); ADCC, antibody dependent cell-mediated cytotoxicity; ANOVA, analysis of variance; FcγRIIIa, Fc gamma receptor IIIa. The figure and caption have been adapted from Kim et al. [36]

Fig. 3

Event-free survival and overall survival among patients receiving reference TRZ, by ADCC status. a Event-free survival by ADCC status, drifted TRZ vs non-drifted TRZ. b Overall survival by ADCC status, drifted TRZ vs non-drifted TRZ. Tick marks represent censored patients. HRs with corresponding 95% CIs and P values were estimated using a stratified Cox proportional hazards regression model. Non-drifted TRZ, patients who were never exposed to any vials from a drifted TRZ lot during the neoadjuvant period. Drifted TRZ, patients who were exposed to at least one vial from a drifted TRZ lot during the neoadjuvant period. ADCC, antibody-dependent cell-mediated cytotoxicity; CI, confidence interval; HR, hazard ratio; TRZ, trastuzumab reference product. The figure and caption have been adapted from Pivot et al. [37]

Fig. 4

Biological activities in SB5 batches. a Fluorescence resonance energy transfer (FRET)-based competitive inhibition binding assay. b Cell-based NFκB-luc reporter gene assay. The figure and caption have been adapted from Lee et al. [38]