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. 2025 Jun;12(3):529-546.
doi: 10.1007/s40744-025-00760-y. Epub 2025 Apr 8.

A Comparison of the Immunogenicity of Intravenous BAT1806, a Tocilizumab Biosimilar, and Its Reference Product

Hans C Ebbers  1 , Peter C Taylor  2 , Xiaomei Leng  3 , Wei Wei  4 , Niamh M Kinsella  5 , Yinbo Zhou  6 , Xiaolei Yang  6 , Paul Chamberlain  7
Affiliations

A Comparison of the Immunogenicity of Intravenous BAT1806, a Tocilizumab Biosimilar, and Its Reference Product

Hans C Ebbers et al. Rheumatol Ther. 2025 Jun.

Abstract

Introduction: Biosimilars need to demonstrate similarity in terms of quality, pharmacokinetics (PK), efficacy, safety, and immunogenicity. Here, we report the outcome of a comprehensive evaluation of the immunogenicity of the biosimilar BAT1806 compared with the tocilizumab reference product (TCZ).

Methods: We conducted a post hoc analysis of study BAT1806-001-CR, a comparative PK study in healthy male volunteers (n = 129), and BAT1806-002-CR, a phase III, 52-week trial in patients with rheumatoid arthritis (n = 621). Anti-drug antibodies (ADA), ADA titers, and neutralizing ADA were measured, and their impact on PK, safety, and efficacy parameters were assessed.

Results: In BAT1806-001-CR, treatment-induced ADA were observed in 37.8% of participants for the BAT1806 group, 28.6% for the EU-sourced TCZ group, and 31.0% for the US-sourced TCZ group, without an impact on PK and safety. In BAT1806-002-CR after 52 weeks, 28.2% of participants in the BAT1806 group developed treatment-induced ADA, compared with 24.0% in the TCZ group and 19.7% of participants who initiated TCZ and switched to BAT1806 at week 24. ADA-positive participants reported lower geometric mean serum tocilizumab trough concentrations than ADA-negative participants in all treatment groups. ADA-positive participants achieved similar efficacy outcomes to ADA-negative participants in all treatment groups. ADA were not associated with an incremental risk of treatment-emergent adverse events or hypersensitivity in any of the treatment groups.

Conclusions: The results of these post hoc analyses did not indicate any clinically relevant differences in the immunogenicity profile of intravenously administered BAT1806 compared with TCZ.

Trial registration: ClinicalTrials.gov identifiers, NCT03606876, NCT03830203.

Keywords: Antibodies; Arthritis; Biosimilar pharmaceuticals; Rheumatoid.

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Conflict of interest statement

Declarations. Conflicts of Interest: Hans C. Ebbers, Wei Wei and Niamh M. Kinsella are Biogen employees and may hold stock, stock options or both in Biogen. Xiaomei Leng has nothing to disclose. Peter C. Taylor has received grant/research support from Galapagos (made to institution); consulting fees and/or honoraria from AbbVie, Biogen, Eli Lilly and Company, Fresenius Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Sanofi, Immunovant and UCB. Yinbo Zhou and Xiaolei Yang are Bio-Thera Solutions Ltd employees and may hold stock, stock options or both in Bio-Thera Solutions Ltd. Paul Chamberlain has received consulting fees from Biogen. Ethical Approval: BAT1806-002-CR was conducted in accordance with the Declaration of Helsinki and/or all relevant local regulations, in compliance with the International Council for Harmonisation Good Clinical Practice guidelines and according to the appropriate regulatory requirements in the countries where the study was conducted. BAT1806-001-CR was approved by The First Bethune Hospital of Jilin University, Changchun, Jilin, China. The patients/participants provided their written informed consent to participate in this study. Patient consent was not applicable for this comparison article.

Figures

Fig. 1
Fig. 1
Box and whiskers plot for ADA titer over time in BAT1806-001-CR. Individual symbols indicate outliers. Lines within boxes = median. Boxes = IQR. Bottom whisker = 25th percentile *IQR. Top whisker = 75th percentile *IQR. Note: One outlier with an ADA titer of 1140 that occurred in the BAT1806 group is not presented in this plot. The safety analysis set contained all participants who received study drug and were analyzed according to treatment received. ADA anti-drug antibody, IQR interquartile range, PK pharmacokinetic, TCZ EU European Union-approved tocilizumab, TCZ US United States-approved tocilizumab
Fig. 2
Fig. 2
Serum tocilizumab concentration over time by ADA (a) and NAb (b) status in BAT1806-001-CR. Lines within boxes = median. Boxes = IQR. Bottom whisker = 25th percentile *IQR. Top whisker = 75th percentile *IQR. Individual symbols indicate outliers. Concentration levels below limit of quantification recorded as '0', were imputed as 0.2 µg/ml, which is the lower limit of quantification. Data from the PK concentration set, which consists of all participants with at least one post-dose evaluable concentration measurement and without protocol violation that significantly influences PK concentration. ADA anti-drug antibody, IQR interquartile range, NAb neutralizing antibody, PK pharmacokinetic, TCZ EU European Union-approved tocilizumab, TCZ US United States-approved tocilizumab
Fig. 3
Fig. 3
Serum tocilizumab trough concentration by ADA status in TP1 and TP2 combined in BAT1806-002-CR. Midpoint = median. Bottom whisker = 25th percentile *IQR. Top whisker = 75th percentile *IQR. Concentration levels below limit of quantification were imputed as 0.2 µg/ml, which is the lower limit of quantification. Note: Five outliers are not presented in the plot given serum concentrations > 150 µg/ml. The PK set included all randomized participants that received any treatment with study drug and had at least one evaluable PK assessment post baseline. Participants were analyzed according to treatment received at the start of TP1 and TP2. ADA anti-drug antibody, IQR interquartile range, PK pharmacokinetic, RoActemra European Union-approved tocilizumab, TP treatment period
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References

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