Ebbers Hans C, Taylor Peter C, Leng Xiaomei, Wei Wei, Kinsella Niamh M, Zhou Yinbo, Yang Xiaolei, Chamberlain Paul
Biogen, Prins Mauritslaan 13-19, PO Box 42, 1170 AA, Badhoevedorp, The Netherlands.
Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Rheumatol Ther. 2025 Jun;12(3):529-546. doi: 10.1007/s40744-025-00760-y. Epub 2025 Apr 8.
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).
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.
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.
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.
ClinicalTrials.gov identifiers, NCT03606876, NCT03830203.
生物类似药需要在质量、药代动力学（PK）、疗效、安全性和免疫原性方面证明相似性。在此，我们报告了生物类似药BAT1806与托珠单抗参比产品（TCZ）相比免疫原性的全面评估结果。
我们对研究BAT1806-001-CR（一项在健康男性志愿者中进行的比较PK研究，n = 129）和BAT1806-002-CR（一项针对类风湿性关节炎患者的III期、为期52周的试验，n = 621）进行了事后分析。测量了抗药物抗体（ADA）、ADA滴度和中和ADA，并评估了它们对PK、安全性和疗效参数的影响。
在BAT1806-001-CR中，BAT1806组37.8%的参与者出现了治疗诱导的ADA，欧盟来源的TCZ组为28.6%，美国来源的TCZ组为31.0%，对PK和安全性无影响。在BAT1806-002-CR中，52周后，BAT1806组28.2%的参与者出现了治疗诱导的ADA，相比之下，TCZ组为24.0%，在第24周开始使用TCZ并转换为BAT1806的参与者为19.7%。在所有治疗组中，ADA阳性参与者的几何平均血清托珠单抗谷浓度低于ADA阴性参与者。在所有治疗组中，ADA阳性参与者的疗效结果与ADA阴性参与者相似。在任何治疗组中，ADA与治疗出现的不良事件或超敏反应的增加风险均无关。
这些事后分析的结果并未表明静脉注射BAT1806与TCZ相比在免疫原性方面存在任何临床相关差异。
ClinicalTrials.gov标识符，NCT03606876，NCT03830203。
