在19例住院的新型冠状病毒肺炎患者中，Calquence显示出有希望的临床改善


Improved laboratory markers of inflammation and decreased oxygen requirements observed in most patients  

正在进行的全球试验旨在证实这些发现

研究结果发表于 科学免疫学 显示, Calquence (acalabrutinib), 布鲁顿酪氨酸激酶(BTK)抑制剂, reduced markers of inflammation and improved clinical outcomes of patients with severe 新型冠状病毒肺炎 disease.1

The peer-reviewed case series of 19 hospitalised patients with 新型冠状病毒肺炎 disease and severe hypoxia and/or inflammation is a collaboration from investigators across the US, 包括澳门在线赌城娱乐的科学家, 由温德姆·威尔逊领导, M.D., Ph.D. 路易斯·施塔特，m.s.D., Ph.D. 在美国国立卫生研究院的国立癌症研究所.

该出版物描述了……的影响 Calquence 由SARS-CoV-2病毒引起的严重呼吸道疾病患者的用药.1 A virus-induced hyperimmune response or “cytokine storm” is hypothesised to be a major pathogenic mechanism of respiratory illness in these patients, and evidence suggests that dysregulated BTK-dependent lung macrophage signalling mediates this cytokine storm and plays a role in 新型冠状病毒肺炎 pneumonia. 2-7

josore Baselga，肿瘤学研究执行副总裁&D博士说:“科学调查支持使用 Calquence 在新型冠状病毒肺炎重症患者中. The encouraging preliminary data in this case series has informed the initiation of global phase II trials, 特别是CALAVI方案. We look forward to completing recruitment and obtaining data in these trials as soon as possible to further our understanding of what this potential treatment could mean for patients.”

Calquence 是下一代, selective BTK inhibitor currently approved in the US for the treatment of certain haematological malignancies.8-10 Calquence 目前尚未在任何国家批准用于治疗与SARS-CoV-2相关疾病的患者.

CALAVI

CALAVI项目包括两个随机的, 非盲, 多中心, 全球试验评估的有效性和安全性 Calquence with best supportive care (BSC) versus BSC alone in patients hospitalised with respiratory complications of 新型冠状病毒肺炎. 这些试验正在评估添加 Calquence 住院但未使用辅助通气的患者的当前BSC. These trials are being conducted around the world: one trial in the US and one trial ex-US including Europe, 日本和南美洲. The primary efficacy endpoint measures the number of patients alive and free of respiratory failure following treatment.11,12

新型冠状病毒肺炎

Coronavirus disease 2019 (新型冠状病毒肺炎) is a new pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 大多数新型冠状病毒肺炎病例(约80%)是轻度呼吸道疾病.13,14 然而, 有些需要住院治疗, 主要是由于肺炎, and can progress quickly to severe acute lung injury and acute respiratory distress syndrome (ARDS), 哪个与高死亡率有关.3,15 A viral-induced “cytokine storm” or hyperimmune response is hypothesised to be a major pathogenic mechanism of ARDS in these patients through modulation of pulmonary macrophages and dendritic cells and/or neutrophils.4,7

Calquence

Calquence 是布鲁顿酪氨酸激酶(BTK)的新一代选择性抑制剂. Calquence 与BTK共价结合，从而抑制其活性.8-10 在b细胞, BTK信号导致b细胞增殖所需通路的激活, 人口贩卖, 趋化性, 和附着力.10

在美国, 澳大利亚, 阿拉伯联合酋长国, 和印度, Calquence is approved for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL), 在加拿大是CLL. Calquence is also approved in the US and a few other countries for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. 该适应症在美国基于总体反应率加速审批. 继续d approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Calquence 目前尚未在任何国家批准用于治疗与SARS-CoV-2相关疾病的患者.

对抑制杀人案

肺巨噬细胞, Bruton’s tyrosine kinase (BTK) is a key regulator of the production of multiple cytokines and chemokines including TNFa, IL-6, IL-10, 和MCP-1, 等.  抑制BTK可减少这些细胞因子的产生, 因此, 这是一种减少新型冠状病毒肺炎呼吸道并发症的有希望的策略.15

T在这里 is evidence that dysregulated BTK-dependent macrophage signalling may be central to the exaggerated inflammatory responses to SARS-COV-2 and play a role in 新型冠状病毒肺炎 pneumonia and acute respiratory distress syndrome (ARDS). 3-6 在巨噬细胞, TLR3, TLR7 and TLR8 can recognise single strand RNA from viruses such as SARS-COV-2 and initiate signalling through BTK-dependent activation of NF-kB and IRF3, 触发多种炎症细胞因子和趋化因子的产生. 4-7 支持BTK抑制的作用, therapeutic inhibition of BTK in patients with lymphoid malignancies results in decreased proinflammatory cytokines and chemokines. 在小鼠流感模型中也观察到类似的结果, w在这里 BTK inhibition also decreased these inflammatory mediators and rescued mice from lethal acute lung injury.

澳门在线赌城娱乐

澳门在线赌城娱乐(LSE/STO/NYSE: AZN)是一家全球性制药公司, 以科学为主导的澳门第一赌城在线娱乐公司，专注于发现, 处方药的开发和商业化, 主要用于治疗肿瘤等三个治疗领域的疾病, 心血管, 肾 & 新陈代谢和呼吸 & 免疫学. 总部设在剑桥, UK, 澳门在线赌城娱乐 operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. 请访问 澳门在线赌城娱乐.com 并在推特上关注公司 @澳门在线赌城娱乐.

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参考文献

  1. Roschewski M等. 布鲁顿酪氨酸激酶在重症新型冠状病毒肺炎患者中的抑制作用. Sci Immunol. 2020;5(28). DOI: 10.1126 / sciimmunol.abd0110.
  2. Conti P，等., Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. 生物调控宿主制剂. 2020;34(2):1. doi: 10.23812 / CONTI-E.
  3. 恰纳帕纳瓦尔等. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. 细胞宿主微生物. 2016;19(2):181-193. doi: 10.1016/j.chom.2016.01.007.
  4. 黄建军，等. SARS患者干扰素- γ相关细胞因子风暴. 医学病毒学. 2005;75(2):185-94. doi: 10.1002 / jmv.20255.
  5. 黄志强，等. 血浆炎症因子和趋化因子与严重急性呼吸综合征的关系. 临床试验免疫. 2004;136(1): 95–103. doi: 10.1111/j.1365-2249.2004.02415.x.
  6. Yoshikawa T，等. Severe Acute 呼吸 Syndrome (SARS) Coronavirus-Induced Lung Epithelial Cytokines Exacerbate SARS Pathogenesis by Modulating Intrinsic Functions of Monocyte-Derived Macrophages and Dendritic Cells. J性研究. 2009;83(7): 3039–3048. 2008年11月12日在线发表. doi: 10.1128 / JVI.01792-08.
  7. Herold S，等. 流感病毒诱导的肺损伤:发病机制和治疗意义. Eur呼吸器. 2015;45(5):1463-78. doi: 10.1183/09031936.00186214.
  8. 吴杰，等. Acalabrutinib (ACP-196):选择性第二代BTK抑制剂. [J]血液学. 2016;9(21).
  9. Khan Y，等. 阿卡拉布替尼及其在慢性淋巴细胞白血病治疗中的应用. 未来的杂志. 2019;15(6):579-589.
  10. CALQUENCE® (acalabrutinib)[处方资料]. Wilmington, DE: 澳门在线赌城娱乐 Pharmaceuticals LP; 2020.
  11. 澳门在线赌城娱乐. Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With 新型冠状病毒肺炎. (CALAVI). 临床试验.政府. 标识符:NCT04346199. 2020年6月.
  12. 澳门在线赌城娱乐. Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With 新型冠状病毒肺炎. (CALAVI澳门第一赌城在线娱乐). 临床试验.政府. 标识符:NCT04380688. 2020年6月.
  13. 黄超，等. 武汉市新型冠状病毒感染患者临床特征分析. 《澳门在线赌城娱乐》. 2020;395:497-506.
  14. 吴志，McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (新型冠状病毒肺炎) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. 《澳门在线赌城娱乐》. 2020年2月24日. doi: 10.1001 /贾马.2020.2648.
  15. 车JJ & 伊莱亚斯L. 布鲁顿酪氨酸激酶(BTK)及其在b细胞恶性肿瘤中的作用. Intl Rev immuno1. 2012;31(2):119-132. doi: 10.3109/08830185.2012.664797.2012.

 

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