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.

新澤西州拉赫韋，2024年10月17日——默克公司（紐約證券交易所代碼：MRK），在美國(guó)和加拿大以外被稱為MSD，今天宣布，該公司的2b/3期臨床試驗(yàn)（MK-1654-004）評(píng)估了clesrovimab的陽(yáng)性結(jié)果，該試驗(yàn)是該公司的研究性預(yù)防性單克隆抗體，旨在保護(hù)嬰兒在第一個(gè)RSV季節(jié)免受呼吸道合胞病毒（RSV）疾病的影響。

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日于加利福尼亞州洛杉磯市舉行的IDWeek 2024會(huì)議上，公布了這些結(jié)果以及正在進(jìn)行的克雷索單抗3期試驗(yàn)（MK-1654-007）的中期結(jié)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是一項(xiàng)安慰劑對(duì)照的2b/3期關(guān)鍵性試驗(yàn)，評(píng)估了對(duì)健康早產(chǎn)兒和足月嬰兒（出生至1歲）服用單劑量克雷珠單抗的結(jié)果，符合所有預(yù)先設(shè)定的終點(diǎn)，在5個(gè)月和6個(gè)月的時(shí)間點(diǎn)都有一致的結(jié)果。clesrovimab組和安慰劑組的不良事件（AE）和嚴(yán)重AE的發(fā)生率相當(dāng)，研究期間沒(méi)有治療或RSV相關(guān)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.

圣裘德兒童研究醫(yī)院傳染病系主任兼MK-1654-004和MK-1654-007試驗(yàn)研究者Octavio Ramilo博士說(shuō)：“RSV仍然是一種廣泛的季節(jié)性感染，可影響健康和高危嬰兒，是嬰兒住院的主要原因?！薄?/p>

“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研究評(píng)估了廣泛的RSV疾病，從輕度門診疾病到需要住院治療的嚴(yán)重疾病。這些有希望的結(jié)果表明RSV疾?。òㄗ≡褐委煟┑陌l(fā)病率降低，突出了克雷珠單抗在幫助減輕RSV對(duì)嬰兒及其家人的持續(xù)負(fù)擔(dān)方面發(fā)揮重要作用的潛力?！薄?/p>

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).

該試驗(yàn)的主要療效終點(diǎn)是，在給藥后第150天（5個(gè)月），與安慰劑相比，需要≥1個(gè)下呼吸道感染（LRI）或嚴(yán)重程度指標(biāo)的RSV相關(guān)醫(yī)學(xué)治療下呼吸道感染（MALRI）的發(fā)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)..

與安慰劑相比，Clesrovimab在第150天（5個(gè)月）也減少了RSV相關(guān)住院（次要終點(diǎn)）和RSV相關(guān)LRI住院（第三終點(diǎn)）84.2%（95%CI:66.6、92.6，p＜0.001）和90.9%（95%CI:76.2、96.5）。Clesrovimab使嚴(yán)重MALRI（三級(jí)終點(diǎn)）的發(fā)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個(gè)月），需要≥2個(gè)LRI和嚴(yán)重程度指標(biāo)（比主要MALRI終點(diǎn)更嚴(yán)重的MALRI終點(diǎn)）的MALRI發(fā)生率降低為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.

下表中按降低疾病嚴(yán)重程度終點(diǎn)的順序列出了來(lái)自RSV疾病負(fù)擔(dān)的MK-1654-004試驗(yàn)數(shù)據(jù)的其他詳細(xì)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住院定義為：RSV PCR陽(yáng)性，因呼吸系統(tǒng)疾病和咳嗽或呼吸困難住院，以及以下至少一種情況：喘息，胸壁向內(nèi)/收縮，羅音/噼啪聲，低氧血癥，呼吸急促，因呼吸系統(tǒng)癥狀引起的脫水。

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

RSV相關(guān)住院定義為：RSV PCR陽(yáng)性和呼吸道疾病住院。

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

次要終點(diǎn)，p<0.001（標(biāo)準(zhǔn)=95%可信區(qū)間的下限>0%）。

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

主要終點(diǎn)，p<0.001（標(biāo)準(zhǔn)=95%可信區(qū)間的下限>25%）。

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

縮寫：LRI=下呼吸道感染；MALRI=醫(yī)療護(hù)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.

默克公司還宣布了計(jì)劃對(duì)MK-1654-007試驗(yàn)進(jìn)行中期分析的數(shù)據(jù)，該試驗(yàn)是一項(xiàng)3期試驗(yàn)，評(píng)估了克雷珠單抗與帕利珠單抗在嚴(yán)重RSV疾病風(fēng)險(xiǎn)增加的嬰兒和兒童中的安全性和有效性。該研究的主要終點(diǎn)是clesrovimab在進(jìn)入第一個(gè)RSV季節(jié)的嬰兒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).

中期結(jié)果顯示，克雷珠單抗的安全性與帕利珠單抗相當(dāng)，迄今為止尚未報(bào)道與藥物相關(guān)的嚴(yán)重AE。在第150天（5個(gè)月），克雷珠單抗（分別為3.6%和1.3%）和帕利珠單抗（分別為3.0%和1.5%）之間，需要≥1個(gè)LRI或嚴(yán)重程度指標(biāo)和RSV相關(guān)住院（次要終點(diǎn)）的RSV相關(guān)MALRI的發(fā)生率也相當(dāng)。

.

.

“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.

默克研究實(shí)驗(yàn)室（Merck Research Laboratories）全球臨床開(kāi)發(fā)部傳染病和疫苗高級(jí)副總裁Paula Annunziato博士說(shuō)：“IDWeek上提供的大量數(shù)據(jù)突顯了clesrovimab有助于減輕RSV對(duì)嬰兒及其家人的重大影響，以及由于高感染率和住院率而對(duì)醫(yī)療保健系統(tǒng)造成的壓力?！薄?/p>

“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.”?.

“這些具有臨床意義的發(fā)現(xiàn)也增強(qiáng)了克萊斯羅維單抗成為第一個(gè)也是唯一一個(gè)旨在保護(hù)使用相同劑量的健康和高危嬰兒的免疫接種的潛力，無(wú)論體重如何。我們期待著繼續(xù)與世界各地的衛(wèi)生當(dāng)局討論這些數(shù)據(jù)，目標(biāo)是最早在2025-26 RSV季節(jié)為嬰兒提供克萊斯羅維單抗?！?。

About MK-1654-004

關(guān)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）是一項(xiàng)2b/3期雙盲，隨機(jī)，安慰劑對(duì)照臨床試驗(yàn)，用于評(píng)估克雷珠單抗在健康早產(chǎn)兒和足月嬰兒中的安全性和有效性，從出生到1歲進(jìn)入他們的第一個(gè)RSV季節(jié)。該研究招募了3632名參與者，他們以2:1的比例隨機(jī)分配，在第1天接受單次固定劑量的克雷珠單抗（105 mg肌肉注射（IM））或安慰劑。

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.

主要終點(diǎn)包括與安慰劑和安全性相比，從第1天（給藥后）到第150天，與RSV相關(guān)的醫(yī)學(xué)治療下呼吸道感染（MALRI）參與者的發(fā)病率。。RSV相關(guān)住院治療至第150天和MALRI需要>1個(gè)LRI指標(biāo)或嚴(yán)重程度至第180天，是預(yù)先指定的次要終點(diǎn)。

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.

預(yù)先設(shè)定的三級(jí)終點(diǎn)包括急性呼吸道感染，RSV相關(guān)的下呼吸道感染住院治療和第150天嚴(yán)重MALRI的發(fā)生率。在事后分析中，評(píng)估了更嚴(yán)重形式的RSV相關(guān)MALRI（>2個(gè)LRI和嚴(yán)重程度指標(biāo)）。在整個(gè)終點(diǎn)，在第180天評(píng)估了其他療效指標(biāo)。

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)..

安全措施包括引發(fā)注射相關(guān)不良事件（AE），特別感興趣的AE（AESI）引發(fā)全身性AE或嚴(yán)重不良事件（SAE）的參與者百分比。。

About MK-1654-007

關(guān)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).

。該研究招募了進(jìn)入第一個(gè)RSV季節(jié)的參與者，并建議由于早產(chǎn)（≤35周胎齡），早產(chǎn)慢性肺?。–LD）或血流動(dòng)力學(xué)顯著的先天性心臟?。–HD）而接受帕利珠單抗治療。

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.

參與者以1:1的比例隨機(jī)接受clesrovimab（第1天105 mg IM，第28天安慰劑）或第一季每月帕利珠單抗，符合條件的參與者在第二個(gè)RSV季節(jié)接受clesrovimab（210 mg IM）。在這項(xiàng)中期分析中，901名參與者參加了試驗(yàn)。主要終點(diǎn)是第一季克雷珠單抗與帕利珠單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. .

次要終點(diǎn)包括呼吸道合胞病毒相關(guān)的下呼吸道感染（MALRI）的發(fā)病率，該感染需要≥1個(gè)LRI或嚴(yán)重程度指標(biāo)，并且在第150天與呼吸道合胞病毒相關(guān)的住院治療。

About clesrovimab (MK-1654)

關(guān)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）是一種研究性延長(zhǎng)半衰期單克隆抗體（mAb），用于預(yù)防RSV的被動(dòng)免疫。Clesrovimab的設(shè)計(jì)是以相同的單劑量給藥，無(wú)論出生體重如何，正在對(duì)健康的早產(chǎn)兒，足月和高危兒進(jìn)行研究，以在其第一個(gè)RSV季節(jié)提供直接，快速和持久的保護(hù)，抵抗輕度，中度和重度RSV。。

About RSV

關(guān)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）是一種傳染性病毒，可引起流感等廣泛的季節(jié)性感染，給嬰兒和老年人帶來(lái)全球負(fù)擔(dān)。健康和高危嬰兒對(duì)預(yù)防選擇的需求都很高。在全球范圍內(nèi)，RSV是一歲以下健康嬰兒住院的主要原因。

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可導(dǎo)致嚴(yán)重的呼吸道疾病，如毛細(xì)支氣管炎和肺炎，估計(jì)全世界每年有101000名5歲以下兒童死亡。根據(jù)疾病預(yù)防控制中心的數(shù)據(jù)，RSV季節(jié)在美國(guó)大多數(shù)地區(qū)始于秋季，冬季達(dá)到高峰，但特定社區(qū)或地區(qū)的時(shí)間和嚴(yán)重程度每年都會(huì)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.

在美國(guó)和加拿大以外被稱為MSD的默克公司，我們的目標(biāo)是團(tuán)結(jié)一致的：我們利用尖端科學(xué)的力量來(lái)拯救和改善世界各地的生活。130多年來(lái)，我們通過(guò)開(kāi)發(fā)重要的藥物和疫苗給人類帶來(lái)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.

我們立志成為世界上領(lǐng)先的研究密集型生物制藥公司，今天，我們處于研究的前沿，以提供創(chuàng)新的健康解決方案，促進(jìn)人類和動(dòng)物疾病的預(yù)防和治療。我們培養(yǎng)了一支多元化和包容性的全球勞動(dòng)力隊(duì)伍，并每天負(fù)責(zé)任地運(yùn)作，為所有人和社區(qū)創(chuàng)造一個(gè)安全、可持續(xù)和健康的未來(lái)。

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