Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the European Commission (EC) has approved WINREVAIR™ (sotatercept), in combination with other pulmonary arterial hypertension (PAH) therapies, for the treatment of PAH in adult patients with World Health Organization (WHO) Functional Class (FC) II to III, to improve exercise capacity.

默克（纽约证券交易所代码：MRK），在美国和加拿大以外被称为MSD，今天宣布，欧盟委员会（EC）已批准WINREVAIR™（sotatercept）与其他肺动脉高压（PAH）疗法联合用于治疗世界卫生组织（WHO）功能II至III级（FC）成年患者的PAH，以提高运动能力。

WINREVAIR is the first and only activin signaling inhibitor therapy for PAH approved in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway. WINREVAIR works by improving the balance between pro- and anti-proliferative signaling to regulate vascular cell proliferation underlying PAH.

WINREVAIR是欧盟所有27个成员国以及冰岛、列支敦士登和挪威批准的第一种也是唯一一种针对PAH的激活素信号抑制剂疗法。WINREVAIR通过改善促增殖和抗增殖信号之间的平衡来调节PAH潜在的血管细胞增殖。

The EC approval of WINREVAIR is based on safety and efficacy results from the Phase 3 STELLAR trial..

欧共体对WINREVAIR的批准是基于STELLAR 3期试验的安全性和有效性结果。

“The European Commission’s approval of WINREVAIR is an important step for patients,” said Dr. Joerg Koglin, senior vice president and head of general medicine, global clinical development, Merck Research Laboratories. “WINREVAIR is the first therapy targeting the activin signaling pathway. We are proud to bring this innovative treatment to more patients and remain committed to further investigating the potential of WINREVAIR in areas where there are unmet needs in the management of PAH.”.

默克研究实验室全球临床开发高级副总裁兼全科医学负责人Joerg Koglin博士说：“欧盟委员会批准WINREVAIR对患者来说是重要的一步。”。“WINREVAIR是第一种针对激活素信号通路的治疗方法。我们很自豪能将这种创新的治疗方法带给更多的患者，并继续致力于进一步研究WINREVAIR在PAH管理需求未得到满足的领域的潜力。”。

“Pulmonary arterial hypertension is a devastating disease for patients, who suffer from debilitating symptoms that can severely limit their daily activities,” said Dr. Marc Humbert, Professor of Medicine and Director of the Pulmonary Hypertension Reference Center at Université Paris-Saclay. “New treatment opinions continue to be needed for patients.

“巴黎-萨克雷大学医学教授兼肺动脉高压参考资料中心主任马克-亨伯博士说："肺动脉高压对患者来说是一种毁灭性疾病，患者的衰弱症状会严重限制他们的日常活动。“患者仍然需要新的治疗方法。

Based on the Phase 3 STELLAR study, adding WINREVAIR to background PAH therapy improved exercise capacity, reduced the risk of death or clinical worsening events and improved functional class compared to background PAH therapy alone. These findings are significant and reinforce that WINREVAIR, in combination with other PAH therapies, should be considered as a new standard of care for the treatment of functional class II and III adult patients.”.

根据STELLAR 3期研究，与单独的背景PAH治疗相比，在背景PAH治疗中加入WINREVAIR可以提高运动能力，降低死亡或临床恶化事件的风险，改善功能分级。这些发现意义重大，并强调WINREVAIR与其他PAH疗法相结合，应被视为治疗功能性II类和III类成年患者的新标准。”。

The EC approval is based on the Phase 3 STELLAR trial, which compared WINREVAIR (n=163) to placebo (n=160), both in combination with background standard of care therapies in adult patients with PAH (WHO Group 1, FC II or III). The primary efficacy endpoint was change from baseline at Week 24 in six-minute walk distance.

EC的批准是基于3期STELLAR试验，该试验比较了WINREVAIR（n=163）和安慰剂（n=160），两者均与成人PAH患者（WHO第1组，FC II或III）的背景护理标准疗法相结合。主要疗效终点是在6分钟步行距离内从第24周的基线变化。

Treatment with WINREVAIR resulted in a statistically significant and clinically meaningful improvement in six-minute walk distance of 40.8 meters over placebo (95% CI: 27.5, 54.1; p<0.001). WINREVAIR also significantly improved multiple important secondary outcome measures, including reducing the risk of death or clinical worsening.

与安慰剂组相比，WINREVAIR治疗组的6分钟步行距离（40.8米）有统计学意义和临床意义的改善（95%可信区间：27.5,54.1；p<0.001）。WINREVAIR还显着改善了多项重要的次要结局指标，包括降低死亡或临床恶化的风险。

In a post hoc analysis provided to EMA, time to death or clinical worsening was defined as the time from randomization to the first occurrence of deterioration of PAH, PAH-specific hospitalization, worsening-related listing for lung and/or heart transplant, need for atrial septostomy, or death from any cause.

在提供给EMA的事后分析中，死亡时间或临床恶化被定义为从随机分组到PAH首次恶化，PAH特异性住院，肺和/或心脏移植相关清单恶化，需要房间隔造口术或任何原因导致的死亡。

There was an 82% reduction in the risk of death or clinical worsening with WINREVAIR on top of background therapy versus background therapy alone (number of events: 7 vs 29, HR=0.182; 95% CI: 0.075, 0.441; p<0.001)..

与单独背景治疗相比，WINREVAIR在背景治疗基础上的死亡或临床恶化风险降低了82%（事件数：7比29，HR=0.182；95%CI:0.075、0.441；p<0.001）。

WINREVAIR is administered once every 3 weeks as a single injection under the skin and may be administered by patients or caregivers with guidance, training and follow-up from a healthcare provider. Healthcare providers and patients/caregivers should refer to the Instructions for Use for information on the proper preparation and administration of WINREVAIR..

WINREVAIR每3周一次，作为皮肤下的单次注射，可由患者或护理人员在医疗保健提供者的指导，培训和随访下进行。医疗保健提供者和患者/护理人员应参考使用说明，了解WINREVAIR的正确制备和管理信息。。

This approval by the EC for WINREVAIR is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway. WINREVAIR was previously granted Priority Medicines (PRIME) and orphan designation by the EMA for the treatment of PAH.

欧共体对WINREVAIR的批准在欧盟所有27个成员国以及冰岛、列支敦士登和挪威均有效。WINREVAIR之前被EMA授予优先药物（PRIME）和孤儿指定用于治疗PAH。

On March 26, 2024, the FDA approved WINREVAIR in the U.S. for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1) to increase exercise capacity, improve WHO functional class (FC) and reduce the risk of clinical worsening events.

2024年3月26日，FDA批准WINREVAIR在美国用于治疗成人肺动脉高压（PAH，WHO第1组），以提高运动能力，改善WHO功能分级（FC）并降低临床恶化事件的风险。

About STELLAR

关于STELLAR

The STELLAR study (NCT04576988) was a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which 323 patients with PAH (WHO Group 1 FC II or III) were randomized 1:1 to WINREVAIR (target dose 0.7 mg/kg) (n=163) or placebo (n=160) plus stable background therapy administered subcutaneously once every 3 weeks..

STELLAR研究（NCT04576988）是一项全球性，双盲，安慰剂对照，多中心，平行组临床试验，其中323名PAH患者（WHO第1组FC II或III）被随机分配到WINREVAIR（目标剂量0.7 mg/kg）（n=163）或安慰剂（n=160）加上每3周皮下一次的稳定背景治疗。。

The most common PAH etiologies were idiopathic PAH (59%), heritable PAH (18%), and PAH associated with connective tissue diseases (CTD) (15%). Most participants were receiving either three (61%) or two (35%) background drugs for PAH, and 40% were receiving prostacyclin infusions. The mean time from PAH diagnosis was 8.8 years.

最常见的PAH病因是特发性PAH（59%），遗传性PAH（18%）和与结缔组织病（CTD）相关的PAH（15%）。大多数参与者正在接受三种（61%）或两种（35%）PAH背景药物，40%正在接受前列环素输注。PAH诊断的平均时间为8.8年。

Patients had a WHO FC II (49%) or III (51%) at baseline..

患者在基线时患有WHO FC II（49%）或III（51%）。。

About WINREVAIR™ (sotatercept-csrk) for injection, for subcutaneous use, 45 mg, 60 mg

关于注射用WINREVAIR™（sotatercept csrk），皮下使用，45毫克，60毫克

WINREVAIR, the first activin signaling inhibitor therapy approved to treat PAH, improves the balance between pro-proliferative and anti-proliferative signaling to modulate vascular proliferation. In preclinical models, WINREVAIR induced cellular changes that were associated with thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics..

WINREVAIR是第一种被批准用于治疗PAH的激活素信号抑制剂疗法，它可以改善促增殖和抗增殖信号之间的平衡，从而调节血管增殖。在临床前模型中，WINREVAIR诱导的细胞变化与血管壁变薄，右心室重塑部分逆转和血流动力学改善有关。。

WINREVAIR is the subject of a licensing agreement with Bristol Myers Squibb.

WINREVAIR与百时美施贵宝签订了许可协议。

Selected Safety Information for WINREVAIR in the U.S.

WINREVAIR在美国的选定安全信息。

WINREVAIR may increase hemoglobin and lead to erythrocytosis. Severe erythrocytosis may increase the risk of thromboembolic events or hyperviscosity syndrome. Monitor Hgb before each dose for the first 5 doses, or longer if values are unstable, and periodically thereafter, to determine if dose adjustments are required..

WINREVAIR可能会增加血红蛋白并导致红细胞增多。严重的红细胞增多症可能会增加血栓栓塞事件或高粘滞综合征的风险。在前5次剂量的每次剂量之前监测Hgb，如果值不稳定，则监测更长时间，然后定期监测Hgb，以确定是否需要调整剂量。。

WINREVAIR may decrease platelet count and lead to severe thrombocytopenia, which may increase the risk of bleeding; thrombocytopenia occurred more frequently in patients also receiving prostacyclin infusion. Do not initiate treatment if platelet count is <50,000/mm.

WINREVAIR可能会降低血小板计数并导致严重的血小板减少症，这可能会增加出血的风险；接受前列环素输注的患者血小板减少症发生率更高。如果血小板计数小于50000/mm，则不要开始治疗。

. Monitor platelets before each dose for the first 5 doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required.

在前5次剂量的每次剂量之前监测血小板，如果值不稳定，则监测更长时间，然后定期监测血小板以确定是否需要调整剂量。

In clinical studies, serious bleeding (e.g., gastrointestinal, intracranial hemorrhage) was reported in 4% of patients taking WINREVAIR and 1% of patients taking placebo. Serious bleeding was more likely in patients on prostacyclin background therapy and/or antithrombotic agents, or with low platelet counts.

在临床研究中，据报道，服用WINREVAIR的患者中有4%出现严重出血（例如胃肠道，颅内出血），服用安慰剂的患者中有1%出现严重出血。服用前列环素背景治疗和/或抗血栓药物或血小板计数低的患者更容易出现严重出血。

Advise patients about signs and symptoms of blood loss. Do not administer WINREVAIR if the patient is experiencing serious bleeding..

告知患者失血的体征和症状。如果患者出现严重出血，请勿服用WINREVAIR。。

WINREVAIR may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with WINREVAIR and for at least 4 months after the final dose. Pregnancy testing is recommended for females of reproductive potential before starting WINREVAIR treatment..

WINREVAIR给孕妇服用时可能会对胎儿造成伤害。告知孕妇对胎儿的潜在风险。建议有生殖潜力的女性在使用WINREVAIR治疗期间以及在最终剂量后至少4个月内使用有效的避孕方法。在开始WINREVAIR治疗之前，建议对具有生殖潜力的女性进行妊娠测试。。

Based on findings in animals, WINREVAIR may impair female and male fertility. Advise patients on the potential effects on fertility.

根据动物的研究结果，WINREVAIR可能会损害女性和男性的生育能力。建议患者对生育能力的潜在影响。

The most common adverse reactions occurring in the Phase 3 clinical trial (≥10% for WINREVAIR and at least 5% more than placebo) were headache (24.5% vs 17.5%), epistaxis (22.1% vs 1.9%), rash (20.2% vs 8.1%), telangiectasia (16.6% vs 4.4%), diarrhea (15.3% vs 10.0%), dizziness (14.7% vs 6.2%), and erythema (13.5% vs 3.1%)..

在3期临床试验中发生的最常见的不良反应（WINREVAIR≥10%，比安慰剂至少多5%）是头痛（24.5%比17.5%），鼻出血（22.1%比1.9%），皮疹（20.2%比8.1%），毛细血管扩张（16.6%比4.4%），腹泻（15.3%比10.0%），头晕（14.7%比6.2%）和红斑（13.5%比3.1%）。。

Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with WINREVAIR, and for 4 months after the final dose.

由于母乳喂养的孩子可能会产生严重的不良反应，因此建议患者在使用WINREVAIR治疗期间以及最终剂量后4个月内不建议母乳喂养。

About pulmonary arterial hypertension (PAH)

关于肺动脉高压（PAH）

Pulmonary arterial hypertension (PAH) is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. Approximately 40,000 people in the U.S. and 30,000 people in the EU are living with PAH.

肺动脉高压（PAH）是一种罕见的，进行性和危及生命的血管疾病，其特征在于小肺动脉收缩和肺循环中的血压升高。美国约有40000人和欧盟约30000人患有PAH。

The disease progresses rapidly for many patients. PAH results in significant strain on the heart, leading to limited physical activity, heart failure and reduced life expectancy. The five-year mortality rate for patients with PAH is approximately 43%, based on data from the REVEAL registry (patients enrolled between March 2006 and December 2009)..

PAH导致心脏严重紧张，导致体力活动受限，心力衰竭和预期寿命缩短。根据REVEAL登记处（2006年3月至2009年12月登记的患者）的数据，PAH患者的五年死亡率约为43%。。

About Merck

默克

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines.

在美国和加拿大以外被称为MSD的默克公司，我们的目标是团结一致的：我们利用尖端科学的力量来拯救和改善世界各地的生活。130多年来，我们通过开发重要的药物和疫苗给人类带来了希望。

We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities.

我们立志成为世界上领先的研究密集型生物制药公司，今天，我们处于研究的前沿，以提供创新的健康解决方案，促进人类和动物疾病的预防和治疗。我们培养了一支多元化和包容性的全球劳动力队伍，并每天负责任地运作，为所有人和社区创造一个安全、可持续和健康的未来。