Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced positive topline results from the Phase 3 CORALreef Lipids trial evaluating the safety and efficacy of enlicitide decanoate, an investigational, once-daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor being evaluated for the treatment of adults with hypercholesterolemia on a moderate or high intensity statin (or with documented statin intolerance)..

默克公司（纽约证券交易所代码：MRK），在美国和加拿大以外地区以MSD名称运营，今天宣布了3期CORALreef Lipids试验的积极顶线结果。该试验评估了在研药物enlicitide decanoate的安全性和有效性，这是一种每日一次口服的前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）抑制剂，用于治疗接受中高强度他汀类药物治疗（或有记录证明无法耐受他汀类药物）的成年高胆固醇血症患者。

The CORALreef Lipids trial successfully met all primary and key secondary endpoints. Treatment with enlicitide resulted in statistically significant and clinically meaningful reduction in low-density lipoprotein cholesterol (LDL-C) compared to placebo at Week 24. Statistically and clinically significant reductions were also seen for enlicitide versus placebo across all key secondary endpoints including in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)].

CORALreef脂质试验成功达到了所有主要和关键的次要终点。与安慰剂相比，使用enlicitide治疗在第24周时显著降低了低密度脂蛋白胆固醇（LDL-C），且具有统计学意义和临床意义。Enlicitide相对于安慰剂，在所有关键次要终点上也显示出统计学和临床意义上的显著降低，包括非高密度脂蛋白胆固醇（non-HDL-C）、载脂蛋白B（ApoB）和脂蛋白(a) [Lp(a)]。

There were no clinically meaningful differences in proportions of participants with adverse events (AE), including serious adverse events (SAE), between treatment groups. Discontinuations due to adverse events were low and comparable between treatment groups..

治疗组之间，发生不良事件（AE）的参与者比例没有临床意义上的差异，包括严重不良事件（SAE）。因不良事件导致的停药率较低，且在治疗组之间具有可比性。

CORALreef Lipids represents the largest completed Phase 3 study evaluating enlicitide in a broad range of participants with elevated LDL-C and a history of or increased risk for major atherosclerotic cardiovascular disease events despite treatment with at least a moderate or high intensity statin (or with documented statin intolerance).

CORALreef Lipids 代表了规模最大的已完成的第三阶段研究，评估了 enlicitide 在广泛参与者中的效果，这些参与者尽管接受至少中等或高强度他汀类药物治疗（或有记录证明的他汀不耐受），但仍然具有高 LDL-C 水平以及主要动脉粥样硬化性心血管疾病事件的历史或高风险。

Merck plans to share these results with regulatory authorities worldwide and will present the data at a future scientific congress..

默克计划与全球监管机构分享这些结果，并将在未来的科学大会上展示这些数据。

“This is the third Phase 3 trial to demonstrate clinically meaningful and statistically significant LDL-C lowering for enlicitide,” said Dr. Dean Y. Li, president, Merck Research Laboratories. 'The advent of injectable PCSK9 inhibitors has enabled a new approach to controlling LDL-C and reducing the risk of atherogenic cardiovascular events.

“这是elicitide在降低LDL-C方面第三次展现出具有临床意义且统计显著的3期试验，”默克研究实验室总裁李恩·Y·迪恩博士表示。“注射型PCSK9抑制剂的出现为控制LDL-C和降低动脉粥样硬化性心血管事件风险提供了新途径。”

Enlicitide, designed to deliver antibody-like efficacy, is the first oral macrocyclic peptide PCSK9 inhibitor with clinically meaningful and statistically significant LDL-C lowering in Phase 3 trials. If approved, it has the potential to change the way we think about managing LDL levels, giving patients the possibility of a new option to help them meet their treatment goals.”.

Enlicitide旨在提供类似抗体的疗效，是首个在三期临床试验中显示出具有临床意义且统计学显著降低LDL-C的口服大环肽PCSK9抑制剂。如果获得批准，它有可能改变我们对管理LDL水平的看法，为患者提供一种新的选择，帮助他们实现治疗目标。

“These data add to the growing body of evidence supporting the safety and efficacy profile of enlicitide to lower LDL cholesterol and other key atherogenic lipids including ApoB and Lp(a),” said Dr. Ann Marie Navar, a lead trial investigator of the study and Associate Professor of Medicine in the Division of Cardiology at UT Southwestern Medical Center.

“这些数据增加了越来越多的证据，支持恩利西肽降低低密度脂蛋白胆固醇和其他关键致动脉粥样硬化脂质（包括ApoB和Lp(a)）的安全性和有效性，”该研究的首席试验研究员、UT西南医学中心心脏病学部医学副教授安妮·玛丽·纳瓦尔博士表示。

“Enlicitide has the potential to help more patients achieve guideline-recommended lipid goals and ultimately reduce atherosclerotic cardiovascular risk, which is currently being evaluated in an ongoing cardiovascular outcomes trial.”.

“Enlicitide有潜力帮助更多患者实现指南推荐的血脂目标，并最终降低动脉粥样硬化性心血管风险，这目前正在一项持续的心血管结局试验中进行评估。”

About CORALreef Lipids

关于珊瑚礁脂质

CORALreef Lipids (

珊瑚礁脂类 (

NCT05952856

NCT05952856

) was a Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety and tolerability of enlicitide decanoate in adults with hypercholesterolemia and a history of a major atherosclerotic cardiovascular disease (ASCVD) event or increased risk for a first event.

）是一项三期随机、双盲、安慰剂对照研究，旨在评估恩利西肽癸酸酯在患有高胆固醇血症且有重大动脉粥样硬化性心血管疾病（ASCVD）事件史或首次事件风险增加的成人中的疗效、安全性和耐受性。

Participants were required to be treated with stable lipid lowering therapies including at least a statin (or have documented statin intolerance). The study’s primary objective was to assess whether enlicitide decanoate was superior to placebo in reducing LDL-C, as measured by mean percent change from baseline at Week 24.

参与者需要接受包括至少一种他汀类药物在内的稳定降脂治疗（或有记录证明的他汀不耐受）。该研究的主要目的是评估依利西肽癸酸酯在降低低密度脂蛋白胆固醇（LDL-C）方面是否优于安慰剂，通过第24周时基线的平均百分比变化来衡量。

Key secondary efficacy endpoints included: change from baseline in LDL-C at week 52 and change from baseline in other key atherogenic lipids at week 24 (non-HDL-C, apolipoprotein B, lipoprotein(a) [Lp(a)])..

关键的次要疗效终点包括：第52周时LDL-C较基线的变化，以及第24周时其他关键致动脉粥样硬化脂质较基线的变化（非HDL-C、载脂蛋白B、脂蛋白(a) [Lp(a)]）。

The efficacy and safety of enlicitide are being evaluated through the comprehensive

通过综合评估来评价恩利西肽的疗效和安全性。

CORALreef Clinical Trial program

CORALreef 临床试验计划

, including the large cardiovascular outcomes trial, CORALreef Outcomes, which has completed enrollment with over 14,500 participants. As previously announced, enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C in both the Phase 3 CORALreef HeFH and CORALreef AddOn trials.

，包括大型心血管结局试验CORALreef Outcomes，该试验已完成超过14,500名参与者的入组。正如之前宣布的，enlicitide在3期CORALreef HeFH和CORALreef AddOn试验中均显示出具有统计学意义且临床意义上显著的LDL-C降低效果。

The CORALreef program reflects Merck’s commitment to advancing research to help address the global burden of atherosclerotic cardiovascular disease..

CORALreef 计划反映了默克公司致力于推进研究，以帮助应对全球动脉粥样硬化性心血管疾病的负担。

About enlicitide and PCSK9

关于enlicitide和PCSK9

Enlicitide is an investigational, potentially first oral PCSK9 inhibitor designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody, injectable PCSK9 inhibitors but in a daily pill form. Enlicitide is a novel small molecule macrocyclic peptide that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors..

Enlicitide是一种研究性药物，有望成为首个口服PCSK9抑制剂，通过与目前已批准的单克隆抗体、注射型PCSK9抑制剂相同的生物学机制来降低LDL-C，但以每日一次的药丸形式给药。Enlicitide是一种新型的小分子大环肽，能够结合PCSK9并抑制PCSK9与LDL受体的相互作用。

PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor, which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 is designed to prevent the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood..

PCSK9通过调节LDL受体的水平在胆固醇稳态中发挥关键作用，LDL受体负责将胆固醇摄入细胞。抑制PCSK9旨在防止PCSK9与LDL受体的相互作用。这使得细胞表面有更多的LDL受体可用于从血液中清除LDL胆固醇。

About hypercholesterolemia

关于高胆固醇血症

Hypercholesterolemia, a type of hyperlipidemia, is a disorder in which there are elevated LDL cholesterol levels in the blood. It affects approximately 86 million adults in the U.S and is a major risk driver for ASCVD, accounting for 85% of cardiovascular deaths. Nearly 70% of people with ASCVD who are treated with lipid lowering therapies do not reach target low-density lipoprotein cholesterol.

高胆固醇血症是一种高脂血症，是指血液中低密度脂蛋白胆固醇水平升高的病症。它影响着美国约8600万成年人，是动脉粥样硬化性心血管疾病（ASCVD）的主要风险因素，占心血管疾病死亡的85%。在接受降脂治疗的ASCVD患者中，近70%的人未能达到目标低密度脂蛋白胆固醇水平。

High LDL-C, if left untreated, can lead to ASCVD events such as heart attacks and strokes..

高LDL-C，如果不治疗，可能导致ASCVD事件，如心脏病发作和中风。

Merck’s focus on cardiovascular disease

默克公司对心血管疾病的专注

Merck has a long history of developing treatments for cardiovascular disease. More than 60 years ago, we introduced our first cardiovascular therapy—and our scientific efforts to understand and treat cardiovascular-related disorders have continued. Cardiovascular disease continues to be one of the most serious health challenges of the 21st century and is the leading cause of death worldwide.

默克公司在开发心血管疾病治疗方法方面有着悠久的历史。60多年前，我们推出了首个心血管疗法，并且我们在理解与治疗心血管相关疾病方面的科学努力一直在继续。心血管疾病仍然是21世纪最严重的健康挑战之一，也是全球死亡的主要原因。

Approximately 18 million people across the globe die from cardiovascular disease every year; in the United States, one person dies every 36 seconds from cardiovascular disease..

全球每年约有1800万人死于心血管疾病；在美国，每36秒就有一人死于心血管疾病。

Advancements in the treatment of cardiovascular disease can make a critical difference for patients and health systems around the world. At Merck, we strive for scientific excellence and innovation in all stages of research, from discovery through approval and life cycle management. We work with experts throughout the cardiovascular and pulmonary community to advance research that can help improve the lives of patients globally..

心血管疾病治疗方面的进步可以为全世界的患者和卫生系统带来关键性的改变。在默克，我们力争在从发现到审批通过及生命周期管理的各个研究阶段中实现科学卓越和创新。我们与心血管和肺部领域的专家合作，推动研究的发展，这有助于改善全球患者的生活。

About Merck

关于默克

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.

在默克（在美国和加拿大以外地区称为MSD），我们围绕一个使命团结一致：我们利用前沿科学的力量来拯救生命并改善世界各地人们的生活。130多年来，我们通过开发重要的药物和疫苗为人类带来了希望。

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.

我们立志成为全球首屈一指的研究密集型生物制药公司——如今，我们在研究领域处于前沿地位，致力于提供创新的健康解决方案，推动人类和动物疾病预防与治疗的进步。我们培养多元化和包容性的全球员工队伍，并每天负责任地运营，以确保为所有人和社区创造一个安全、可持续和健康的未来。