WILMINGTON, Del.--(BUSINESS WIRE)--The Phase IIa COURSE trial was a proof-of-concept study in people with moderate to very severe chronic obstructive pulmonary disease (COPD) with a broad range of blood eosinophil counts (BEC) and irrespective of emphysema, chronic bronchitis or smoking status.1 The primary results showed that treatment with AstraZeneca and Amgen’s TEZSPIRE® (tezepelumab) led to a 17% numerical reduction in the annual rate of moderate or severe COPD exacerbations compared to placebo at week 52, which was not statistically significant (90% CI (Confidence Interval): -6, 36], p [1-sided]=0.1042).1 The results are being presented at the American Thoracic Society (ATS) International Conference..

威尔明顿，德尔。-（商业新闻短讯）--IIa期课程试验是一项概念验证研究，针对中度至非常重度慢性阻塞性肺疾病（COPD）患者，其血液嗜酸性粒细胞计数（BEC）范围广泛，与肺气肿，慢性支气管炎或吸烟状况无关。1主要结果显示，与安慰剂相比，在第52周，阿斯利康和安进的TEZSPIRE®（tezepelumab）治疗导致中度或重度COPD恶化的年发生率降低了17%，这在统计学上不显着（90%CI（置信区间）：-6,36），p[单侧]=0.1042）.1研究结果将在美国胸科学会（ATS）国际会议上发表。。

Importantly, in patients with BEC ≥150 cells/µL, tezepelumab led to a nominally significant reduction of 37% in the rate of moderate or severe exacerbations compared to placebo.1 Studies suggest that approximately 65% of bio-eligible patients with COPD have a BEC greater than or equal to 150 cells/μL.2 In patients with BEC ≥300 cells/µL tezepelumab led to a numerical reduction of 46% in the rate of moderate or severe exacerbations.1 (Table 1.).

重要的是，在BEC≥150个细胞/μL的患者中，与安慰剂相比，替赛普单抗导致中度或重度恶化率名义上显着降低37%.1研究表明，大约65%符合生物条件的COPD患者BEC大于或等于150个细胞/μL.2在BEC≥300个细胞/μL的患者中，替赛普单抗导致中度或重度恶化率的数字降低46%[1]（表1）。

Dr Dave Singh, Professor of Respiratory Pharmacology at the University of Manchester and lead investigator on the trial, said: “I believe that biologics will play a critical role in the future care of COPD and trials such as the tezepelumab COURSE trial are central to understanding and shaping the treatment landscape.

曼彻斯特大学呼吸药理学教授兼该试验首席研究员戴夫·辛格博士说：“我相信生物制剂将在未来的COPD护理中发挥关键作用，而诸如替赛普单抗疗程试验等试验对于理解和塑造治疗前景至关重要。

The tezepelumab COURSE results are particularly important as they show activity in COPD across a broad patient population including those with baseline blood eosinophil counts greater than 150 cells/μL.”.

tezepelumab疗程结果特别重要，因为它们显示了广泛患者人群中COPD的活性，包括基线血嗜酸性粒细胞计数大于150个细胞/μL的患者。”。

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “These proof-of-concept results from the COURSE trial are encouraging as they signal the potential efficacy of tezepelumab in a broad range of people with COPD irrespective of emphysema, chronic bronchitis and smoking status.

阿斯利康生物制药研发部执行副总裁莎伦·巴尔（SharonBarr）表示：“这些来自课程试验的概念验证结果令人鼓舞，因为它们表明，无论肺气肿，慢性支气管炎和吸烟状况如何，替塞匹单抗在广泛的COPD患者中都具有潜在的疗效。

As a result of these promising data, we are actively in Phase III planning for tezepelumab in COPD.”.

由于这些有希望的数据，我们正在积极参与COPD中替塞匹单抗的III期计划。”。

A subgroup analysis of the COURSE trial also showed treatment with tezepelumab resulted in numerical improvements in lung function as measured by forced expiratory volume (FEV1) (improvement of 63mL and 146mL in BEC ≥150 and ≥300 cells/μL respectively, compared to placebo) and in quality of life as measured by the St.

COURSE试验的亚组分析还显示，通过用力呼气量（FEV1）测量，用替塞单抗治疗可导致肺功能的数值改善（与安慰剂相比，BEC≥150和≥300细胞/μL分别改善63mL和146mL）和生活质量。

George’s Respiratory Questionnaire (SGRQ) score (reduction of 4.2 points and 9.5 points in BEC ≥150 and ≥300 cells/μL respectively).1 The safety and tolerability profile for tezepelumab was consistent with its approved severe asthma indication; the most frequently reported (>10%) adverse events for tezepelumab were worsening of COPD (12.1%) and incidents of COVID-19 infections (14.5%) (this trial commenced in July 2019).1 (Table 2.).

George的呼吸问卷（SGRQ）评分（BEC≥150和≥300个细胞/μL分别降低4.2分和9.5分）[1]。替塞单抗的安全性和耐受性与其批准的严重哮喘适应症一致；替塞单抗最常报告的不良事件（>10%）是COPD恶化（12.1%）和COVID-19感染事件（14.5%）（该试验于2019年7月开始）.1（表2）。

COURSE Phase IIa analysis:

课程第二阶段A分析：

Table 1: Tezepelumab impact on COPD exacerbations versus placebo over 52 weeks1

表1:52周内替塞单抗与安慰剂相比对COPD急性加重的影响1

Reduction in exacerbations compared to placebo

与安慰剂相比，急性发作减少

Annualized rate of exacerbations

年恶化率

Moderate or severe exacerbations

中度或重度恶化

Overall population (n=333)

总人口（n=333）

17% (90% CI: -6, 36)

17%（90%置信区间：-6,36）

1.75 in tezepelumab group versus 2.11 in placebo group

替赛普单抗组为1.75，安慰剂组为2.11

BEC less than 150 cells/μL (n=137)

BEC小于150个细胞/升（n=137）

-19% (95% CI: -90, 25)

-19%（95%置信区间：-90,25）

2.04 in tezepelumab group versus 1.71 in placebo group

替赛普单抗组为2.04，安慰剂组为1.71

BEC greater than or equal to 150 cells/μL (n=196)

BEC大于或等于150个细胞/μL（n=196）

37% (95% CI: 7, 57)

37%（95%置信区间：7,57）

1.52 in tezepelumab group versus 2.40 in placebo group

替赛普单抗组为1.52，安慰剂组为2.40

BEC greater than or equal to 300 cells/μL (n=56)

BEC大于或等于300个细胞/μL（n=56）

46% (95% CI: -15, 75)

46%（95%置信区间：-15,75）

1.20 in tezepelumab group versus 2.24 in placebo group

替赛普单抗组为1.20，安慰剂组为2.24

Severe exacerbations

严重恶化

Overall population (n=333)

总人口（n=333）

48% (95% CI: -11, 76)

48%（95%置信区间：-11,76）

0.13 in tezepelumab group versus 0.25 in placebo group

替赛普单抗组为0.13，安慰剂组为0.25

Table 2: Tezepelumab impact on quality of life and lung function versus placebo over 52 weeks1

表2:52周内，与安慰剂相比，替赛普单抗对生活质量和肺功能的影响1

Lung function as measured by pre-bronchodilator forced expiratory volume (FEV1, µL)

通过支气管扩张剂前用力呼气量（FEV1，L）测量肺功能

Quality of life improvement as measured by St. George’s Respiratory Questionnaire (SGRQ) score

圣乔治呼吸问卷（SGRQ）评分衡量的生活质量改善

Tezepelumab

特zepelumab

(n)/LS Mean

（n） /LS平均值

Placebo

安慰剂

(n)/LS

（n） /升

Mean

平均值

LS mean

LS平均值

difference

差异

(95% CI)

（95%置信区间）

Tezepelumab

特zepelumab

(n)/LS Mean

（n） /LS平均值

Placebo

安慰剂

(n)/LS

（n） /升

Mean

平均值

LS mean

LS平均值

difference

差异

(95% CI)

（95%置信区间）

BEC less than 150 cells/μL

BEC小于150个细胞/μL

73/-0.002

73/-0.002

63/-0.053

63/-0.053

0.051 (-0.012,0.114)

0.051 (-0.012,0.114)

69/-1.91

69/-1.91

60/-0.30

60/-0.30

-1.62 (-6.69, 3.45)

-1.62 (-6.69, 3.45)

BEC greater than or equal to 150 cells/μL

BEC大于或等于150个细胞/μL

90/0.049

90/0.049

103/-0.014

103/-0.014

0.063 (0.009, 0.116)

0.063 (0.009, 0.116)

88/-7.08

88/-7.08

96/-2.85

96/-2.85

-4.23 (-8.51, 0.06)

-4.23 (-8.51, 0.06)

BEC counts greater than or equal to 300 cells/μL

BEC计数大于或等于300个细胞/μL

24/0.160

24/0.160

31/0.013

31/0.013

0.146 (0.044, 0.248)

0.146 (0.044, 0.248)

22/-10.22

22/-10.22

27/-0.68

27/-0.68

-9.53 (-18.11, -0.96)

-9.53 (-18.11, -0.96)

INDICATIONS AND LIMITATIONS OF USE / ISI

使用指示和限制/ISI

TEZSPIRE® (tezepelumab)

TEZSPIRES® （tezepelumab）

CONTRAINDICATIONS

禁忌症

Known hypersensitivity to tezepelumab-ekko or excipients.

已知对替塞匹单抗ekko或赋形剂过敏。

WARNINGS AND PRECAUTIONS

警告和注意事项

Hypersensitivity Reactions

超敏反应

Hypersensitivity reactions were observed in the clinical trials (eg, rash and allergic conjunctivitis) following the administration of TEZSPIRE. Postmarketing cases of anaphylaxis have been reported. These reactions can occur within hours of administration, but in some instances have a delayed onset (ie, days).

在服用TEZSPIRE后的临床试验（例如皮疹和过敏性结膜炎）中观察到超敏反应。已经报道了上市后的过敏反应病例。这些反应可能在给药后数小时内发生，但在某些情况下会延迟发作（即数天）。

In the event of a hypersensitivity reaction, consider the benefits and risks for the individual patient to determine whether to continue or discontinue treatment with TEZSPIRE..

如果出现超敏反应，请考虑个体患者的益处和风险，以确定是否继续或停止使用TEZSPIRE治疗。。

Acute Asthma Symptoms or Deteriorating Disease

急性哮喘症状或疾病恶化

TEZSPIRE should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus.

TEZSPIRE不应用于治疗急性哮喘症状，急性加重，急性支气管痉挛或哮喘状态。

Abrupt Reduction of Corticosteroid Dosage

皮质类固醇剂量突然减少

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with TEZSPIRE. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy..

在开始使用TEZSPIRE治疗时，不要突然停止全身或吸入皮质类固醇。如果适当的话，皮质类固醇剂量的减少应该是逐渐的，并在医生的直接监督下进行。皮质类固醇剂量的减少可能与全身性戒断症状和/或先前被全身性皮质类固醇治疗抑制的掩盖状况有关。。

Parasitic (Helminth) Infection

寄生虫感染

It is unknown if TEZSPIRE will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with TEZSPIRE. If patients become infected while receiving TEZSPIRE and do not respond to anti-helminth treatment, discontinue TEZSPIRE until infection resolves..

目前尚不清楚TEZSPIRE是否会影响患者对蠕虫感染的反应。在开始用TEZSPIRE治疗之前，先治疗已有蠕虫感染的患者。如果患者在接受TEZSPIRE治疗时感染，并且对抗蠕虫治疗无反应，则停止使用TEZSPIRE，直到感染消退。。

Live Attenuated Vaccines

减毒活疫苗

The concomitant use of TEZSPIRE and live attenuated vaccines has not been evaluated. The use of live attenuated vaccines should be avoided in patients receiving TEZSPIRE.

尚未评估同时使用TEZSPIRE和减毒活疫苗。接受TEZSPIRE治疗的患者应避免使用减毒活疫苗。

ADVERSE REACTIONS

不良反应

The most common adverse reactions (incidence ≥3%) are pharyngitis, arthralgia, and back pain.

最常见的不良反应（发生率≥3%）是咽炎，关节痛和背痛。

USE IN SPECIFIC POPULATIONS

在特定人群中使用

There are no available data on TEZSPIRE use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy..

目前还没有关于孕妇使用TEZSPIRE的可用数据来评估任何与药物相关的重大出生缺陷，流产或其他不良孕产妇或胎儿结局的风险。在妊娠晚期，胎盘转移单克隆抗体如替塞单抗ekko更大；因此，在妊娠晚期，对胎儿的潜在影响可能更大。。

INDICATION

指示

TEZSPIRE is indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.

TEZSPIRE适用于12岁及以上患有严重哮喘的成人和儿科患者的附加维持治疗。

TEZSPIRE is not indicated for the relief of acute bronchospasm or status asthmaticus.

TEZSPIRE不适用于缓解急性支气管痉挛或哮喘状态。

Please see full Prescribing Information, including Patient Information and Instructions for Use.

请参阅完整的处方信息，包括患者信息和使用说明。

You may report side effects related to AstraZeneca products.

您可能会报告与阿斯利康产品有关的副作用。

Notes

注意事项

COURSE Phase IIa trial

课程IIa期试验

COURSE was a Phase IIa multicentre, randomized, double-blind, placebo-controlled, parallel group trial designed to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving triple inhaled maintenance therapy, and having had two or more documented COPD exacerbations in the 12 months prior to Visit 1.

该课程是一项IIa期多中心，随机，双盲，安慰剂对照，平行组试验，旨在评估替塞单抗在接受三重吸入维持治疗的中度至重度慢性阻塞性肺疾病（COPD）成人中的安全性和有效性，并且在第1次访视前的12个月内有两次或更多记录的COPD恶化。

A total of 337 patients were randomized globally, with patients stratified by region and prior number of exacerbations (two vs. three or more). Patients received tezepelumab 420 mg, or placebo, administered via subcutaneous injection at the trial site every four weeks over a 52-week treatment period.

共有337名患者在全球范围内随机分组，患者按地区和先前的恶化次数分层（两次对三次或更多）。患者在52周的治疗期内，每四周在试验部位皮下注射一次替赛普单抗420 mg或安慰剂。

The trial included a post-treatment follow-up period of 12 weeks.1,3.

该试验包括12周的治疗后随访期。

Chronic Obstructive Pulmonary Disease (COPD)

慢性阻塞性肺疾病（COPD）

COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems.4 COPD is the third leading cause of death due to chronic disease and the sixth leading cause of mortality in the United States. COPD accounts for the majority of chronic lower respiratory mortality in the US at 150,000 deaths per year, and data suggests patients with COPD are, on average, 50 times more likely to die from their condition compared to those with asthma.5,6.

COPD是指一组引起气流阻塞和呼吸相关问题的肺部疾病，包括慢性支气管炎和肺气肿。4 COPD是美国慢性病死亡的第三大原因，也是死亡率的第六大原因。COPD占美国慢性下呼吸道死亡率的大部分，每年有15万人死亡，数据表明，与哮喘患者相比，COPD患者死于疾病的可能性平均高出50倍[5,6]。

The lungs and heart are fundamentally linked and work together.7 COPD mechanisms elevate the risk of both lung and heart events, including severe or even fatal COPD exacerbations and cardiac events, known as cardiopulmonary risk.8-11 Approximately 1 in 5 patients with COPD will die within a year of their first hospitalization for an exacerbation, and pulmonary and cardiac events are a key driver of mortality and the most common reasons for death in patients with COPD.8,12-14.

肺和心脏从根本上是联系在一起的[7]。COPD机制会增加肺和心脏事件的风险，包括严重甚至致命的COPD恶化和心脏事件，称为心肺风险[8-11]。大约五分之一的COPD患者将在首次住院后一年内因恶化而死亡，肺和心脏事件是COPD患者死亡的关键驱动因素和最常见的死亡原因[8,12-14]。

TEZSPIRE

TEZSPIRE

TEZSPIRE (tezepelumab) is being developed by AstraZeneca in collaboration with Amgen as a first-in-class human monoclonal antibody that inhibits the action of TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of allergic, eosinophilic and other types of airway inflammation associated with severe asthma, including airway hyperresponsiveness.15,16 TEZSPIRE is approved in the US, EU, Japan and other countries for the treatment of severe asthma.17-19.

TEZSPIRE（tezepelumab）是由阿斯利康公司与安进公司合作开发的一种一流的人类单克隆抗体，可抑制TSLP的作用，TSLP是一种关键的上皮细胞因子，位于多种炎症级联反应的顶部，对过敏，嗜酸性粒细胞和其他类型与严重哮喘相关的气道炎症的发生和持续至关重要，包括气道高反应性[15,16]。TEZSPIRE在美国，欧盟，日本和其他国家被批准用于治疗严重哮喘[17-19]。

Amgen collaboration

安进合作

In 2020, Amgen and AstraZeneca updated a 2012 collaboration agreement for TEZSPIRE. Both companies will continue to share costs and profits equally after payment by AstraZeneca of a mid single-digit inventor royalty to Amgen. AstraZeneca continues to lead development and Amgen continues to lead manufacturing.

2020年，安进和阿斯利康为TEZSPIRE更新了2012年的合作协议。阿斯利康（AstraZeneca）向安进（Amgen）支付了一笔中个位数的发明家专利使用费后，两家公司将继续平等分享成本和利润。阿斯利康继续领导发展，安进继续领导制造业。

All aspects of the collaboration are under the oversight of joint governing bodies. Under the amended agreement, Amgen and AstraZeneca will jointly commercialize TEZSPIRE in North America. Amgen will record product sales in the US, with AZ recording its share of US profits as Collaboration Revenue. Outside of the US, AstraZeneca will record product sales, with Amgen recording profit share as Other/Collaboration revenue..

合作的所有方面都在联合理事机构的监督下。根据修订后的协议，安进和阿斯利康将在北美共同将TEZSPIRE商业化。安进（Amgen）将记录美国的产品销售额，而安智（AZ）将其在美国的利润份额记录为合作收入。在美国之外，阿斯利康将记录产品销售，安进将利润份额记录为其他/合作收入。。

In addition, we are also collaborating with AstraZeneca on AMG104/AZD8630, an inhaled anti-TSLP compound currently in development for asthma. In November 2021, Amgen and AstraZeneca agreed to include AMG 104 / AZD8630 in the existing collaboration agreement. The companies share both costs and income, with no inventor royalty.

此外，我们还与阿斯利康合作开发AMG104/AZD8630，这是一种目前正在开发用于哮喘的吸入性抗TSLP化合物。2021年11月，安进和阿斯利康同意将AMG 104/AZD8630纳入现有的合作协议。这两家公司分担成本和收入，没有发明家专利使用费。

AstraZeneca will be the development, manufacturing and commercial lead. AstraZeneca and Amgen will jointly commercialize AMG 104 / AZD8630 in North America, and AstraZeneca will distribute the product and book sales globally, including for the US..

阿斯利康将成为开发、制造和商业领域的领导者。阿斯利康和安进将在北美联合商业化AMG 104/AZD8630，阿斯利康将在全球（包括美国）分销产品和书籍销售。。

Respiratory & Immunology

呼吸与免疫学

Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca’s main disease areas and is a key growth driver for the Company.

呼吸与免疫学是生物制药的一部分，是阿斯利康的主要疾病领域之一，也是该公司增长的关键驱动因素。

AstraZeneca is an established leader in respiratory care with a 50-year heritage. The Company aims to transform the treatment of asthma and COPD by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. The Company’s early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction..

阿斯利康是呼吸护理领域公认的领导者，拥有50年的历史。该公司旨在通过专注于早期的生物学主导治疗，消除可预防的哮喘发作，并将COPD作为前三大死亡原因，从而改变哮喘和COPD的治疗方法。该公司的早期呼吸研究专注于新兴科学，涉及免疫机制，肺损伤以及疾病和神经元功能障碍中异常的细胞修复过程。。

With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Company’s growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases.

阿斯利康在呼吸和免疫学领域有着共同的途径和潜在的疾病驱动因素，正在遵循从慢性肺病到免疫学驱动疾病领域的科学。该公司在免疫学领域的发展主要集中在五个具有多种疾病潜力的中晚期特许经营权上，这些领域包括风湿病（包括系统性红斑狼疮），皮肤病，胃肠病和系统性嗜酸性粒细胞驱动的疾病。

AstraZeneca’s ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide..

阿斯利康在呼吸与免疫学领域的目标是为全球数百万患者实现疾病缓解和持久缓解。。

About AstraZeneca

关于阿斯利康

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide.

阿斯利康是一家以科学为主导的全球生物制药公司，专注于肿瘤学、罕见病和生物制药（包括心血管、肾脏和代谢以及呼吸和免疫学）处方药的发现、开发和商业化。阿斯利康总部位于英国剑桥，在100多个国家开展业务，其创新药物被全球数百万患者使用。

For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca..

欲了解更多信息，请访问www.astrazeneca-us.com，并在社交媒体@astrazeneca上关注我们。。

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