MSD announces Phase III data on investigational treatment to lower LDL Cholesterol (LDL-C)

LONDON, UK, 8th November 2025 – MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA (NYSE: MRK)) 

MSD announced the first presentation of results from the Phase III CORALreef Lipids Trial, which demonstrated that Enlicitide Decanoate (enlicitide), an Investigational Oral PCSK9 Inhibitor, was associated with a significant reduction in LDL Cholesterol (LDL-C).

The data shows that adults with or at-risk for atherosclerotic cardiovascular disease (ASCVD) on background lipid lowering therapies, or with a documented statin intolerance, who received once-daily oral enlicitide had statistically significant and clinically meaningful reductions in LDL-C at week 24 (primary endpoint) and statistically significant and sustained reductions in LDL-C through one year (week 52).iii Enlicitide has the potential to be the first approved oral PCSK9 inhibitor to lower LDL-C, and demonstrated a safety profile comparable to placebo in this trial.

There are around 640 million people living with cardiovascular disease (CVD) around the world.v It is the world's leading cause of death, with 1 in 3 deaths globally caused by CVD.v It also has a high burden of disease in the UK, causing more than 170,000 deaths annually, which represents over a quarter (26%) of all deaths.iv 

Of all of deaths caused by CVD globally, ASCVD accounts for 85%.ii ASCVD is caused by the buildup of plaque in the arteries, which can occur as a result of excess LDL-C.i

Jasveen Chugh, Executive Director and Head of Pharmaceutical Medicines at MSD in the UK, said: “Cardiovascular disease represents a growing public health threat both globally and within the UK. With ASCVD responsible for approximately 85% of all cardiovascular deaths worldwide,ii there is a need for new treatment options, and this data represents a promising step forward.”

Please note that enlicitide deconoate is an investigational medicine, meaning that it does not have a license in the UK or any other country and cannot currently be prescribed.

About atherosclerotic cardiovascular disease

Cardiovascular disease (CVD) is an umbrella term for a range of condition affecting the heart and blood vessels. There are around 640 million people living with CVD around the world, and it is the world's leading cause of death.[v] 1 in 3 deaths globally are caused by CVD.v Of these, atherosclerotic cardiovascular disease (ASCVD) accounts for 85% of all CVD deaths.ii

‘Atherosclerotic’ refers to CVD which is caused by atherosclerosis – the buildup of plaque (composing fats, cholesterol and other substances) on and in the artery walls.[vi] This results in the narrowing of the arteries, restricting the flow of blood.[vii] This can result in serious cardiovascular events including heart attacks, strokes, peripheral artery disease, and other types of CVD.vii

About hypercholesterolaemia

Hypercholesterolaemia is a disorder in which there are elevated low-density lipoprotein (LDL) cholesterol levels in the blood.[viii] It is a major risk factor for ASCVD.i High LDL cholesterol, if left untreated, can lead to ASCVD events such as heart attacks and strokes.viii

About enlicitide and PCSK9

Enlicitide is designed to lower LDL-C via a similar biological mechanism as those existing PCSK9 inhibitors which are administered via injection, but in a daily pill form. Enlicitide is a small molecule macrocyclic peptide candidate that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.

Enlicitide deconoate is an investigational medicine, meaning that it does not have a license in the UK or any other country and currently cannot be prescribed.

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.[ix] Inhibition of PCSK9 is designed to prevent the interaction of PCSK9 with LDL receptors.ix This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.ix

About CORALreef Clinical Trial Programme

The efficacy and safety profile of enlicitide is being evaluated through the comprehensive CORALreef Clinical Trial programme evaluating over 18,000 participants who have hypercholesterolemia. The three pivotal Phase 3 studies in the programme are CORALreef Lipids (NCT05952856)[x], CORALreef HeFH (NCT05952869)[xi] and CORALreef AddOn (NCT06450366)[xii].

Enlicitide is continuing to be evaluated in the cardiovascular outcomes trial, CORALreef Outcomes (NCT06008756)[xiii], which has completed enrollment with over 14,500 participants. Additional CORALreef clinical trials include CORALreef Extension (NCT06492291)[xiv], CORALreef Pediatric (NCT07058077)[xv] and CORALreef Combination (NCT07216482)[xvi].

About MSD

At MSD, known as Merck & Co., Inc., Rahway, NJ, USA in 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. 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.  For more information, visit www.msd-uk.com and connect with us @MSDintheUK on X (formerly Twitter), LinkedIn,  Instagram, YouTube and Facebook.  

MSD has a long history of developing treatments for cardiovascular disease. Nearly 70 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. Approximately 18 million people across the globe die from cardiovascular disease every year.

Advancements in the treatment of cardiovascular disease can make a critical difference for patients and health systems around the world. At MSD, 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.