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评估生物类似药ABP 654与优特克单抗在克罗恩病患者样本中的功能相似性。

Assessing Functional Similarity of Biosimilar ABP 654 and Ustekinumab in Samples from Patients with Crohn's Disease.

作者信息

Foltz Ian N, Gaida Kevin, Wong Helen Y, Ng Michael, Busch Marijana, Liu Jennifer L

机构信息

Amgen Research, Department of Therapeutic Discovery, Amgen Inc., Burnaby, BC, V5A1V7, Canada.

Research and Development, Amgen Inc., Thousand Oaks, CA, 91320, USA.

出版信息

J Inflamm Res. 2024 Dec 7;17:10627-10640. doi: 10.2147/JIR.S478529. eCollection 2024.

DOI:10.2147/JIR.S478529
PMID:39670154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11635162/
Abstract

PURPOSE

ABP 654 is the first FDA-approved interchangeable biosimilar for ustekinumab reference product (RP). To support the totality of evidence (TOE), in vitro pharmacology studies were conducted in peripheral blood mononuclear cells (PBMCs) from healthy human donors and Crohn's disease (CD) patients to evaluate IL-23 and IL-12 inhibition by ABP 654 and ustekinumab RP relevant to the mechanism of action of chronic inflammation.

METHODS

ABP 654 and ustekinumab RP were assessed using inhibition of IL-23 and IL-12-mediated IFN-γ release, signal transducer and activator of transcription (STAT)3 and STAT4 phosphorylation, and IL-17 release. IFN-γ levels were determined using homogenous time-resolved fluorescence (HTRF). STAT3 and STAT4 phosphorylation were measured by flow cytometry. IL-17 was measured using a Cisbio IL-17 detection kit. IC values were calculated to assess the relative potency of ABP 654 and ustekinumab RP.

RESULTS

ABP 654 and ustekinumab RP demonstrated similar inhibition and relative potency of IL-23 and IL-12-mediated IFN-γ release, and no difference in inhibition of IL-23/IL-12-mediated STAT3/STAT4 phosphorylation in healthy donor PBMCs, as evidenced by the overlapping standard deviation (SD). In CD PBMCs, ABP 654 and ustekinumab RP also showed no difference in IC values for inhibition of IL-23/IL-12-mediated STAT3/STAT4 phosphorylation. ABP 654 and ustekinumab RP showed no difference in IC values for IL-23-induced IL-17 release, in either healthy (ABP 654, 458.7±110.8 pM; ustekinumab (EU), 514.6±48.7 pM) or CD (ABP 654, 260.8±88.5 pM; ustekinumab (EU), 256.9±96.8 pM) donor cells with overlapping SD.

CONCLUSION

These studies demonstrated similar inhibition of IL-23 and IL-12 function by ABP 654 and ustekinumab RP in both healthy and CD PBMCs. Overall, these assays support the conclusion that ABP 654 and ustekinumab RP are functionally similar, thereby contributing to the TOE supporting a demonstration of biosimilarity.

摘要

目的

ABP 654是首个获美国食品药品监督管理局（FDA）批准的可互换的优特克单抗参比产品（RP）生物类似药。为支持整体证据（TOE），开展了体外药理学研究，以评估ABP 654和优特克单抗参比产品对来自健康人类供体和克罗恩病（CD）患者的外周血单个核细胞（PBMC）中白细胞介素-23（IL-23）和白细胞介素-12（IL-12）的抑制作用，这些作用与慢性炎症的作用机制相关。

方法

使用对IL-23和IL-12介导的γ干扰素（IFN-γ）释放、信号转导和转录激活因子（STAT）3和STAT4磷酸化以及IL-17释放的抑制作用来评估ABP 654和优特克单抗参比产品。使用均相时间分辨荧光（HTRF）法测定IFN-γ水平。通过流式细胞术测量STAT3和STAT4磷酸化。使用Cisbio IL-17检测试剂盒测量IL-17。计算半数抑制浓度（IC）值以评估ABP 654和优特克单抗参比产品的相对效价。

结果

ABP 654和优特克单抗参比产品在IL-23和IL-12介导的IFN-γ释放抑制方面表现出相似的抑制作用和相对效价，并且在健康供体PBMC中对IL-23/IL-12介导的STAT3/STAT4磷酸化的抑制作用无差异，重叠标准差（SD）证明了这一点。在CD患者的PBMC中，ABP 654和优特克单抗参比产品在抑制IL-23/IL-12介导的STAT3/STAT4磷酸化的IC值方面也无差异。在健康供体（ABP 654，458.7±110.8 pM；优特克单抗（欧盟），514.6±48.7 pM）或CD患者（ABP 654，260.8±88.5 pM；优特克单抗（欧盟），256.9±96.8 pM）的细胞中，ABP 654和优特克单抗参比产品在IL-23诱导的IL-17释放的IC值方面无差异，SD重叠。

结论

这些研究表明，ABP 654和优特克单抗参比产品在健康和CD患者的PBMC中对IL-23和IL-12功能的抑制作用相似。总体而言，这些试验支持ABP 654和优特克单抗参比产品在功能上相似的结论，从而有助于支持生物类似性证明的整体证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/fa0e49122361/JIR-17-10627-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/5728b1781e72/JIR-17-10627-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/00daebb02bf8/JIR-17-10627-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/3ebee819e120/JIR-17-10627-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/ccee23aed5ee/JIR-17-10627-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/82e702ba7242/JIR-17-10627-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/fa0e49122361/JIR-17-10627-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/5728b1781e72/JIR-17-10627-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/8e0ded85b0e3/JIR-17-10627-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/00daebb02bf8/JIR-17-10627-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/3ebee819e120/JIR-17-10627-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/ccee23aed5ee/JIR-17-10627-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/82e702ba7242/JIR-17-10627-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e11/11635162/fa0e49122361/JIR-17-10627-g0007.jpg

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