RAHWAY, N.J., Oct. 17, 2024 – Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the presentation of positive results from the Phase 2b/3 clinical trial (MK-1654-004) evaluating clesrovimab, the company’s investigational prophylactic monoclonal antibody designed to protect infants from respiratory syncytial virus (RSV) disease during their first RSV season.

新泽西州拉赫韦，2024年10月17日——默克公司（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，该公司的2b/3期临床试验（MK-1654-004）评估了clesrovimab的阳性结果，该试验是该公司的研究性预防性单克隆抗体，旨在保护婴儿在第一个RSV季节免受呼吸道合胞病毒（RSV）疾病的影响。

The results, along with interim findings from the ongoing Phase 3 trial (MK-1654-007) of clesrovimab, were presented during IDWeek 2024, held October 16-19 in Los Angeles, California..

在10月16日至19日于加利福尼亚州洛杉矶市举行的IDWeek 2024会议上，公布了这些结果以及正在进行的克雷索单抗3期试验（MK-1654-007）的中期结果。

Results from MK-1654-004, a placebo-controlled Phase 2b/3 pivotal trial evaluating a single dose of clesrovimab administered to healthy preterm and full-term infants (birth to 1 year of age) met all prespecified endpoints, with consistent results through both the 5-month and 6-month time points. The incidence of adverse events (AEs) and serious AEs were comparable between the clesrovimab and placebo groups, and there were no treatment or RSV-related deaths during the study..

MK-1654-004是一项安慰剂对照的2b/3期关键性试验，评估了对健康早产儿和足月婴儿（出生至1岁）服用单剂量克雷珠单抗的结果，符合所有预先设定的终点，在5个月和6个月的时间点都有一致的结果。clesrovimab组和安慰剂组的不良事件（AE）和严重AE的发生率相当，研究期间没有治疗或RSV相关死亡。。

“RSV continues to be a widespread seasonal infection that can affect both healthy and at-risk infants and is the leading cause of hospitalization for infants,” said Dr. Octavio Ramilo, chair of the Department of Infectious Diseases at St. Jude’s Children’s Research Hospital and investigator for the MK-1654-004 and MK-1654-007 trials.

圣裘德儿童研究医院传染病系主任兼MK-1654-004和MK-1654-007试验研究者Octavio Ramilo博士说：“RSV仍然是一种广泛的季节性感染，可影响健康和高危婴儿，是婴儿住院的主要原因。”。

“The MK-1654-004 study evaluated a broad spectrum of RSV disease ranging from mild outpatient illness to severe disease requiring hospitalization. These promising results demonstrating decreased incidence of RSV disease, including hospitalizations, highlight the potential for clesrovimab to play an important role in helping to alleviate the continued burden of RSV on infants and their families.”.

“MK-1654-004研究评估了广泛的RSV疾病，从轻度门诊疾病到需要住院治疗的严重疾病。这些有希望的结果表明RSV疾病（包括住院治疗）的发病率降低，突出了克雷珠单抗在帮助减轻RSV对婴儿及其家人的持续负担方面发挥重要作用的潜力。”。

The primary efficacy endpoint of the trial, the reduction in incidence of RSV-associated medically attended lower respiratory infections (MALRI) requiring ≥ 1 indicator of lower respiratory infection (LRI) or severity compared to placebo through Day 150 (5 months) postdose, was 60.4% (95% CI: 44.1, 71.9, p<0.001).

该试验的主要疗效终点是，在给药后第150天（5个月），与安慰剂相比，需要≥1个下呼吸道感染（LRI）或严重程度指标的RSV相关医学治疗下呼吸道感染（MALRI）的发生率降低了60.4%（95%CI:44.1,71.9，p＜0.001）。

Clesrovimab also reduced RSV-associated hospitalizations (secondary endpoint) and RSV-associated LRI hospitalizations (tertiary endpoint) through Day 150 (5 months) compared to placebo by 84.2% (95% CI: 66.6, 92.6, p<0.001) and 90.9% (95% CI: 76.2, 96.5), respectively. Clesrovimab reduced the incidence of severe MALRI (tertiary endpoint) by 91.7% (95% CI: 62.9, 98.1)..

与安慰剂相比，Clesrovimab在第150天（5个月）也减少了RSV相关住院（次要终点）和RSV相关LRI住院（第三终点）84.2%（95%CI:66.6、92.6，p＜0.001）和90.9%（95%CI:76.2、96.5）。Clesrovimab使严重MALRI（三级终点）的发生率降低了91.7%（95%CI:62.9，98.1）。。

In addition, in a post hoc analysis, the reduction in incidence of MALRI requiring ≥ 2 indicators of LRI and severity (an endpoint of more severe MALRI than the primary MALRI endpoint), was 88.0% (95% CI: 76.1, 94.0) through Day 150 (5 months).

此外，在事后分析中，在第150天（5个月），需要≥2个LRI和严重程度指标（比主要MALRI终点更严重的MALRI终点）的MALRI发生率降低为88.0%（95%CI:76.194.0）。

Additional details on the data from the MK-1654-004 trial across RSV disease burden are presented in order of decreasing disease severity endpoints in the tables below.

下表中按降低疾病严重程度终点的顺序列出了来自RSV疾病负担的MK-1654-004试验数据的其他详细信息。

Full Analysis Set Population.

完整分析集人口。

LRI Hospitalization defined as: RSV PCR positive AND hospital admission for respiratory illness AND cough or difficulty breathing AND at least 1 of the following: wheezing, chest wall indrawing/retractions, rales/crackles, hypoxemia, tachypnea, dehydration due to respiratory symptoms.

LRI住院定义为：RSV PCR阳性，因呼吸系统疾病和咳嗽或呼吸困难住院，以及以下至少一种情况：喘息，胸壁向内/收缩，罗音/噼啪声，低氧血症，呼吸急促，因呼吸系统症状引起的脱水。

RSV-associated Hospitalization defined as: RSV PCR positive AND hospital admission for respiratory illness.

RSV相关住院定义为：RSV PCR阳性和呼吸道疾病住院。

Secondary endpoint, p<0.001 (criterion=lower bound of the 95% CI >0%).

次要终点，p<0.001（标准=95%可信区间的下限>0%）。

Primary endpoint, p<0.001 (criterion=lower bound of the 95% CI >25%).

主要终点，p<0.001（标准=95%可信区间的下限>25%）。

Abbreviations: LRI=Lower Respiratory Infection; MALRI=Medically Attended Lower Respiratory Infection; ARI=Acute Respiratory Infection.

缩写：LRI=下呼吸道感染；MALRI=医疗护理的下呼吸道感染；ARI=急性呼吸道感染。

Merck also announced data from a planned interim analysis of the MK-1654-007 trial, a Phase 3 trial evaluating the safety and efficacy of clesrovimab versus palivizumab in infants and children at increased risk for severe RSV disease. The primary endpoint of the study is the safety and tolerability of clesrovimab in infants entering their first RSV season.

默克公司还宣布了计划对MK-1654-007试验进行中期分析的数据，该试验是一项3期试验，评估了克雷珠单抗与帕利珠单抗在严重RSV疾病风险增加的婴儿和儿童中的安全性和有效性。该研究的主要终点是clesrovimab在进入第一个RSV季节的婴儿中的安全性和耐受性。

Interim results showed clesrovimab had a comparable safety profile to palivizumab, and no drug-related serious AEs were reported to date. Incidence rates of RSV-associated MALRI requiring ≥ 1 indicator of LRI or severity and RSV-associated hospitalizations (secondary endpoints) were also comparable between clesrovimab (3.6% and 1.3%, respectively) and palivizumab (3.0% and 1.5%, respectively) through Day 150 (5 months).

中期结果显示，克雷珠单抗的安全性与帕利珠单抗相当，迄今为止尚未报道与药物相关的严重AE。在第150天（5个月），克雷珠单抗（分别为3.6%和1.3%）和帕利珠单抗（分别为3.0%和1.5%）之间，需要≥1个LRI或严重程度指标和RSV相关住院（次要终点）的RSV相关MALRI的发生率也相当。

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“The breadth of data presented at IDWeek highlight the potential for clesrovimab to help lessen the significant impact RSV can have on infants and their families, as well as the strain on healthcare systems due to high infection and hospitalization rates,” said Dr. Paula Annunziato, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories.

默克研究实验室（Merck Research Laboratories）全球临床开发部传染病和疫苗高级副总裁Paula Annunziato博士说：“IDWeek上提供的大量数据突显了clesrovimab有助于减轻RSV对婴儿及其家人的重大影响，以及由于高感染率和住院率而对医疗保健系统造成的压力。”。

“These clinically meaningful findings also reinforce the potential for clesrovimab to be the first and only immunization designed to protect both healthy and at-risk infants using the same dose, regardless of weight. We look forward to continuing to discuss these data with health authorities around the world with the goal of making clesrovimab available for infants as early as the 2025-26 RSV season.” .

“这些具有临床意义的发现也增强了克莱斯罗维单抗成为第一个也是唯一一个旨在保护使用相同剂量的健康和高危婴儿的免疫接种的潜力，无论体重如何。我们期待着继续与世界各地的卫生当局讨论这些数据，目标是最早在2025-26 RSV季节为婴儿提供克莱斯罗维单抗。”‡。

About MK-1654-004

关于MK-1654-004

MK-1654-004 (NCT04767373) is a Phase 2b/3 double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of clesrovimab in healthy preterm and full-term infants from birth to 1 year of age entering their first RSV season. The study enrolled 3,632 participants who were randomized 2:1 to receive either a single fixed dose of clesrovimab (105 mg intramuscular injection (IM)) or placebo on Day 1.

MK-1654-004（NCT04767373）是一项2b/3期双盲，随机，安慰剂对照临床试验，用于评估克雷珠单抗在健康早产儿和足月婴儿中的安全性和有效性，从出生到1岁进入他们的第一个RSV季节。该研究招募了3632名参与者，他们以2:1的比例随机分配，在第1天接受单次固定剂量的克雷珠单抗（105 mg肌肉注射（IM））或安慰剂。

Primary endpoints included the incidence of participants with RSV-associated medically attended lower respiratory infection (MALRI) from Day 1 (postdose) to Day 150 as compared to placebo and safety. The MALRI definition required >1 indicator of LRI or severity. RSV-associated hospitalization through Day 150 and MALRI requiring >1 indicator of LRI or severity to Day 180, were prespecified secondary endpoints.

主要终点包括与安慰剂和安全性相比，从第1天（给药后）到第150天，与RSV相关的医学治疗下呼吸道感染（MALRI）参与者的发病率。。RSV相关住院治疗至第150天和MALRI需要>1个LRI指标或严重程度至第180天，是预先指定的次要终点。

Prespecified tertiary endpoints included acute respiratory infection, RSV-associated lower respiratory infection hospitalizations and incidence of severe MALRI through Day 150. In a post hoc analysis, more severe forms of RSV-associated MALRI (>2 indicators of LRI and severity) were assessed. Across endpoints, additional measures of efficacy were assessed through Day 180.

预先设定的三级终点包括急性呼吸道感染，RSV相关的下呼吸道感染住院治疗和第150天严重MALRI的发生率。在事后分析中，评估了更严重形式的RSV相关MALRI（>2个LRI和严重程度指标）。在整个终点，在第180天评估了其他疗效指标。

Safety measures included the percentage of participants with solicited injection-related adverse events (AEs), AEs of special interest (AESIs) solicited systemic AEs or serious adverse events (SAEs)..

安全措施包括引发注射相关不良事件（AE），特别感兴趣的AE（AESI）引发全身性AE或严重不良事件（SAE）的参与者百分比。。

About MK-1654-007

关于MK-1654-007

MK-1654-007 (NCT04938830) is a Phase 3, multicenter, randomized, partially blinded, controlled study to evaluate the safety, efficacy, and pharmacokinetics of clesrovimab in infants and children at increased risk for severe RSV disease compared to palivizumab. The study enrolled participants who were entering their first RSV season and recommended to receive palivizumab due to prematurity (≤35 weeks gestational age), chronic lung disease (CLD) of prematurity, or hemodynamically significant congenital heart disease (CHD).

。该研究招募了进入第一个RSV季节的参与者，并建议由于早产（≤35周胎龄），早产慢性肺病（CLD）或血流动力学显着的先天性心脏病（CHD）而接受帕利珠单抗治疗。

Participants were randomized 1:1 to receive clesrovimab (105 mg IM on Day 1, placebo on Day 28) or monthly palivizumab in their first season, and eligible participants received clesrovimab (210 mg IM) in the second RSV season. At this interim analysis, 901 participants were enrolled in the trial. The primary endpoint is safety and tolerability of clesrovimab versus palivizumab in the first season.

参与者以1:1的比例随机接受clesrovimab（第1天105 mg IM，第28天安慰剂）或第一季每月帕利珠单抗，符合条件的参与者在第二个RSV季节接受clesrovimab（210 mg IM）。在这项中期分析中，901名参与者参加了试验。主要终点是第一季克雷珠单抗与帕利珠单抗的安全性和耐受性。

Secondary endpoints include the incidence of RSV-associated medically attended lower respiratory infections (MALRI) requiring ≥1 indicator of LRI or severity and of RSV-associated hospitalization through Day 150. .

次要终点包括呼吸道合胞病毒相关的下呼吸道感染（MALRI）的发病率，该感染需要≥1个LRI或严重程度指标，并且在第150天与呼吸道合胞病毒相关的住院治疗。

About clesrovimab (MK-1654)

关于clesrovimab（MK-1654）

Clesrovimab (MK-1654) is an investigational, extended half-life monoclonal antibody (mAb) developed as a passive immunization for the prevention of RSV. Clesrovimab is designed to be administered as the same single dose, regardless of birth weight, and is being studied in healthy preterm, full-term and at-risk infants to provide direct, rapid, and durable protection through their first RSV season against mild, moderate and severe RSV..

Clesrovimab（MK-1654）是一种研究性延长半衰期单克隆抗体（mAb），用于预防RSV的被动免疫。Clesrovimab的设计是以相同的单剂量给药，无论出生体重如何，正在对健康的早产儿，足月和高危儿进行研究，以在其第一个RSV季节提供直接，快速和持久的保护，抵抗轻度，中度和重度RSV。。

About RSV

关于RSV

Respiratory syncytial virus (RSV) is a contagious virus that causes widespread seasonal infections like the flu, with a worldwide burden in infants and older adults. There is high unmet need for preventative options in both healthy and high-risk infants. Globally, RSV is the leading cause of hospitalization for healthy infants under a year old.

呼吸道合胞病毒（RSV）是一种传染性病毒，可引起流感等广泛的季节性感染，给婴儿和老年人带来全球负担。健康和高危婴儿对预防选择的需求都很高。在全球范围内，RSV是一岁以下健康婴儿住院的主要原因。

RSV can lead to serious respiratory conditions like bronchiolitis and pneumonia, causing an estimated 101,000 deaths a year worldwide in children under five. According to the CDC, RSV season starts in the fall and peaks in the winter in most regions of the United States, but timing and severity in a given community or region can vary year to year..

RSV可导致严重的呼吸道疾病，如毛细支气管炎和肺炎，估计全世界每年有101000名5岁以下儿童死亡。根据疾病预防控制中心的数据，RSV季节在美国大多数地区始于秋季，冬季达到高峰，但特定社区或地区的时间和严重程度每年都会有所不同。。

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。