重磅！Evusheld长效抗体组合在欧盟获批，用于广泛人群的新冠病毒暴露前预防
来源：生物谷 2022-03-29 18:58
III期PROVENT试验表明，Evusheld能够显著降低发生有症状新冠感染的风险，保护作用至少持续6个月。
2022年3月29日，阿斯利康Evusheld（tixagevimab替沙格韦单抗与cilgavimab西加韦单抗组合）是一种长效抗体组合，已获准在欧盟上市，用于成年人和青少年（12岁及以上且体重40公斤及以上）广泛人群的新冠病毒暴露前预防。
基于Evusheld临床开发项目获得的结果，欧盟委员会批准Evusheld在欧洲上市。Evusheld临床研究结果包括 来自III期PROVENT暴露前预防试验的数据，该试验初步分析显示，与安慰剂相比，使用Evusheld的受试者发生有症状新冠感染的相对风险降低了77%；中位随访6个月分析显示，有症状新冠感染的相对风险降低了83%；保护作用至少持续6个月。Evusheld在临床试验中显示出良好的耐受性。
德国慕尼黑工业大学兼职讲学教授、伊萨尔大学医院传染病和流行病顾问医师、医学博士Christoph D. Spinner表示：“高度传染性的BA.2亚变异株病例数量仍在不断增加，但是很多公共卫生疫情防控措施被撤销，这使得保护易感人群，如免疫功能低下的人群免受新冠病毒感染变得非常重要。Evusheld获批用于广泛人群，这将使得欧盟国家卫生部门能够确定需要额外优先保护的高危人群。”
阿斯利康执行副总裁、生物制药研发负责人Mene Pangalos表示：“Evusheld在欧盟获批是我们预防新冠感染工作的一个重要里程碑，我们将继续与欧洲各国政府合作，尽快推动Evusheld上市。Evusheld能为没有得到新冠疫苗充分保护的广泛人群提供持久保护，如不能充分受到新冠疫苗保护的人群，以及病毒暴露风险较高的人群。”
Evusheld在欧洲的推荐剂量为150 毫克 tixagevimab替沙格韦单抗 + 150 毫克cilgavimab西加韦单抗，两种抗体分开给药，连续肌肉注射。
越来越多独立的体外和体内（动物模型）研究证据支持Evusheld可以有效预防正在全球流行的BA.1、BA.1.1和BA.2新冠病毒奥密克戎（Omicron）亚变异株。来自华盛顿大学医学院的最新数据表明，Evusheld对BA.2具有强效中和活性，该亚变异株具有高度传染性，是许多欧洲国家的最常见的毒株，目前占欧洲新冠感染病例总数的近60%。 该研究还表明，Evusheld降低了所有奥密克戎变异株的病毒负荷并减轻了肺部（体内研究）炎症。
Evusheld在美国获得应急使用授权，并在英国药品和保健品管理局（MHRA）获得附条件上市许可，批准Evusheld用于新冠病毒暴露前预防。此外，阿斯利康已经与欧洲许多国家达成协议，向其提供Evusheld。
不能充分受到新冠疫苗保护的人群尤其可能从Evusheld提供的暴露前预防中受益。此类人群包括欧盟约 300 万免疫功能低下的人，例如癌症患者、移植患者或服用免疫抑制药物的患者。新冠病毒暴露风险更高的人群同样可能从Evusheld提供的保护中受益。
Evusheld是唯一在III期临床试验中被证明能够有效预防和治疗新冠病毒感染的长效抗体组合。阿斯利康正在全球范围内申请Evusheld用于新冠预防和治疗的紧急使用授权或上市批准。
参考文献：
1，US Food and Drug Administration. FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR EVUSHELDTM (tixagevimab co-packaged with cilgavimab). Available at: https://www.fda.gov/media/154701/download [Last accessed March 2022].
2，AstraZeneca news release. AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html [Last accessed: March 2022].
3，AstraZeneca news release. New analyses of two AZD7442 COVID-19 trials in high-risk populations confirm robust efficacy and long-term prevention. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/new-analyses-of-two-azd7442-covid-19-phase-iii-trials-in-high-risk-populations-confirm-robust-efficacy-and-long-term-prevention.html. [Last accessed: March 2022]
4，Dejnirattisai W, et al. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Cell. 2022;185(3):467-484.e15.
5，VanBlargan LA, et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nature Medicine. 2022; 28:490-495.
6，Case, J et al. Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains. Available at: https://www.biorxiv.org/content/10.1101/2022.03.17.484787v1 [Last accessed March 2022].
7，COVID CG. (2022). GISAID. Available at: https://covidcg.org/?groupKey=lineage®ion=Europe&residueCoordinates=1%2C1274&selectedGene=S&tab=group [Last accessed: March 2022].
8，Centers for Disease Control and Prevention. Altered Immunocompetence. General Best Practice Guideline for Immunization: Best Practices Guidance of the Advisory Committee on Immunization Practices. Available at: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html [Last accessed: March 2022]
9，Boyarsky BJ, et al. Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA. 2021; 325 (17):1784-1786.
10，Rabinowich L, et al. Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients. J Hepatol. 2021; 75(2):435-438.
11，Deepak P, et al. Glucocorticoids and B cell depleting agents substantially impair immunogenicity of mRNA vaccines to SARS-CoV-2. medRxiv [Preprint]. 2021 Apr 9:2021.04.05.21254656. doi: 10.1101/2021.04.05.21254656.
12，Simon D, et al. SARS-CoV-2 vaccination responses in untreated, conventionally treated and anticytokine-treated patients with immune-mediated inflammatory diseases. Ann Rheum Dis. 2021; 80(10):1312–1316.
13，AstraZeneca Data on File.
14，Centers of Disease Control and Prevention. Risk Factors of Exposure to COVID-19: Racial and Ethnic Health Disparities. 2020. Available from: https://www.cdc.gov/coronavirus/2019-ncov/community/health-equity/racial-ethnic-disparities/increased-risk-exposure.html. [Last accessed: March 2022].
15，AstraZeneca news release. Evusheld reduced risk of developing severe COVID-19 or death in TACKLE Phase III outpatient treatment trial. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/Evusheld-phiii-trial-positive-in-covid-outpatients.html. [Last accessed: March 2022].
16，Dong J, et al. Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail. bioRxiv. 2021; doi: 10.1101/2021.01.27.428529.
17，Robbie GJ, et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013; 57 (12): 6147-53.
18，Griffin MP, et al. Safety, tolerability, and pharmacokinetics of MEDI8897, the respiratory syncytial virus prefusion F-targeting monoclonal antibody with an extended half-life, in healthy adults. Antimicrob Agents Chemother. 2017; 61(3): e01714-16.
19，Domachowske JB, et al. Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. Pediatr Infect Dis J. 2018; 37(9): 886-892.
20，van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.
基于Evusheld临床开发项目获得的结果，欧盟委员会批准Evusheld在欧洲上市。Evusheld临床研究结果包括 来自III期PROVENT暴露前预防试验的数据，该试验初步分析显示，与安慰剂相比，使用Evusheld的受试者发生有症状新冠感染的相对风险降低了77%；中位随访6个月分析显示，有症状新冠感染的相对风险降低了83%；保护作用至少持续6个月。Evusheld在临床试验中显示出良好的耐受性。
德国慕尼黑工业大学兼职讲学教授、伊萨尔大学医院传染病和流行病顾问医师、医学博士Christoph D. Spinner表示：“高度传染性的BA.2亚变异株病例数量仍在不断增加，但是很多公共卫生疫情防控措施被撤销，这使得保护易感人群，如免疫功能低下的人群免受新冠病毒感染变得非常重要。Evusheld获批用于广泛人群，这将使得欧盟国家卫生部门能够确定需要额外优先保护的高危人群。”
阿斯利康执行副总裁、生物制药研发负责人Mene Pangalos表示：“Evusheld在欧盟获批是我们预防新冠感染工作的一个重要里程碑，我们将继续与欧洲各国政府合作，尽快推动Evusheld上市。Evusheld能为没有得到新冠疫苗充分保护的广泛人群提供持久保护，如不能充分受到新冠疫苗保护的人群，以及病毒暴露风险较高的人群。”
Evusheld在欧洲的推荐剂量为150 毫克 tixagevimab替沙格韦单抗 + 150 毫克cilgavimab西加韦单抗，两种抗体分开给药，连续肌肉注射。
越来越多独立的体外和体内（动物模型）研究证据支持Evusheld可以有效预防正在全球流行的BA.1、BA.1.1和BA.2新冠病毒奥密克戎（Omicron）亚变异株。来自华盛顿大学医学院的最新数据表明，Evusheld对BA.2具有强效中和活性，该亚变异株具有高度传染性，是许多欧洲国家的最常见的毒株，目前占欧洲新冠感染病例总数的近60%。 该研究还表明，Evusheld降低了所有奥密克戎变异株的病毒负荷并减轻了肺部（体内研究）炎症。
Evusheld在美国获得应急使用授权，并在英国药品和保健品管理局（MHRA）获得附条件上市许可，批准Evusheld用于新冠病毒暴露前预防。此外，阿斯利康已经与欧洲许多国家达成协议，向其提供Evusheld。
不能充分受到新冠疫苗保护的人群尤其可能从Evusheld提供的暴露前预防中受益。此类人群包括欧盟约 300 万免疫功能低下的人，例如癌症患者、移植患者或服用免疫抑制药物的患者。新冠病毒暴露风险更高的人群同样可能从Evusheld提供的保护中受益。
Evusheld是唯一在III期临床试验中被证明能够有效预防和治疗新冠病毒感染的长效抗体组合。阿斯利康正在全球范围内申请Evusheld用于新冠预防和治疗的紧急使用授权或上市批准。
参考文献：
1，US Food and Drug Administration. FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR EVUSHELDTM (tixagevimab co-packaged with cilgavimab). Available at: https://www.fda.gov/media/154701/download [Last accessed March 2022].
2，AstraZeneca news release. AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html [Last accessed: March 2022].
3，AstraZeneca news release. New analyses of two AZD7442 COVID-19 trials in high-risk populations confirm robust efficacy and long-term prevention. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/new-analyses-of-two-azd7442-covid-19-phase-iii-trials-in-high-risk-populations-confirm-robust-efficacy-and-long-term-prevention.html. [Last accessed: March 2022]
4，Dejnirattisai W, et al. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Cell. 2022;185(3):467-484.e15.
5，VanBlargan LA, et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nature Medicine. 2022; 28:490-495.
6，Case, J et al. Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains. Available at: https://www.biorxiv.org/content/10.1101/2022.03.17.484787v1 [Last accessed March 2022].
7，COVID CG. (2022). GISAID. Available at: https://covidcg.org/?groupKey=lineage®ion=Europe&residueCoordinates=1%2C1274&selectedGene=S&tab=group [Last accessed: March 2022].
8，Centers for Disease Control and Prevention. Altered Immunocompetence. General Best Practice Guideline for Immunization: Best Practices Guidance of the Advisory Committee on Immunization Practices. Available at: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html [Last accessed: March 2022]
9，Boyarsky BJ, et al. Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA. 2021; 325 (17):1784-1786.
10，Rabinowich L, et al. Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients. J Hepatol. 2021; 75(2):435-438.
11，Deepak P, et al. Glucocorticoids and B cell depleting agents substantially impair immunogenicity of mRNA vaccines to SARS-CoV-2. medRxiv [Preprint]. 2021 Apr 9:2021.04.05.21254656. doi: 10.1101/2021.04.05.21254656.
12，Simon D, et al. SARS-CoV-2 vaccination responses in untreated, conventionally treated and anticytokine-treated patients with immune-mediated inflammatory diseases. Ann Rheum Dis. 2021; 80(10):1312–1316.
13，AstraZeneca Data on File.
14，Centers of Disease Control and Prevention. Risk Factors of Exposure to COVID-19: Racial and Ethnic Health Disparities. 2020. Available from: https://www.cdc.gov/coronavirus/2019-ncov/community/health-equity/racial-ethnic-disparities/increased-risk-exposure.html. [Last accessed: March 2022].
15，AstraZeneca news release. Evusheld reduced risk of developing severe COVID-19 or death in TACKLE Phase III outpatient treatment trial. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/Evusheld-phiii-trial-positive-in-covid-outpatients.html. [Last accessed: March 2022].
16，Dong J, et al. Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail. bioRxiv. 2021; doi: 10.1101/2021.01.27.428529.
17，Robbie GJ, et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013; 57 (12): 6147-53.
18，Griffin MP, et al. Safety, tolerability, and pharmacokinetics of MEDI8897, the respiratory syncytial virus prefusion F-targeting monoclonal antibody with an extended half-life, in healthy adults. Antimicrob Agents Chemother. 2017; 61(3): e01714-16.
19，Domachowske JB, et al. Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. Pediatr Infect Dis J. 2018; 37(9): 886-892.
20，van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.
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