静脉注射托西珠单抗生物仿制药 BAT1806 与其参照产品的免疫原性比较

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2025-04-08 DOI:10.1007/s40744-025-00760-y

Hans C Ebbers, Peter C Taylor, Xiaomei Leng, Wei Wei, Niamh M Kinsella, Yinbo Zhou, Xiaolei Yang, Paul Chamberlain

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引用次数: 0

摘要

生物仿制药需要在质量、药代动力学（PK）、疗效、安全性和免疫原性方面证明相似性。在这里，我们报告了生物仿制药BAT1806与托珠单抗参考产品（TCZ）的免疫原性综合评估结果。方法：我们对BAT1806-001-CR研究进行了回顾性分析，BAT1806-001-CR是一项在健康男性志愿者中进行的比较PK研究（n = 129）， BAT1806-002-CR是一项在类风湿关节炎患者中进行的为期52周的III期试验（n = 621）。测定抗药物抗体（ADA）、ADA滴度和中和性ADA，并评估其对PK、安全性和有效性参数的影响。结果：在BAT1806-001- cr中，BAT1806组37.8%的参与者观察到治疗性ADA，欧盟来源的TCZ组28.6%，美国来源的TCZ组31.0%，对PK和安全性没有影响。在BAT1806-002- cr中，52周后，BAT1806组中28.2%的参与者发生了治疗性ADA，而TCZ组中这一比例为24.0%，而在第24周开始使用TCZ并切换到BAT1806的参与者中这一比例为19.7%。在所有治疗组中，ada阳性受试者报告的几何平均血清托珠单抗谷浓度低于ada阴性受试者。在所有治疗组中，ada阳性受试者与ada阴性受试者取得了相似的疗效结果。在任何治疗组中，ADA均与治疗中出现的不良事件或过敏的风险增加无关。结论：这些事后分析的结果没有显示静脉注射BAT1806与TCZ相比在免疫原性方面有任何临床相关的差异。试验注册：ClinicalTrials.gov识别码，NCT03606876, NCT03830203。

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

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.

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来源期刊

Rheumatology and Therapy RHEUMATOLOGY-

CiteScore

6.00

自引率

5.30%

发文量

审稿时长

6 weeks

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