In short
Enlicitide decanoate (also known as MK-0616) is an investigational oral medicine that inhibits PCSK9, a protein involved in cholesterol regulation. It is being studied in four EU clinical trials covering hyperlipidemia, atherosclerotic cardiovascular disease, elevated lipoprotein(a), and heterozygous familial hypercholesterolemia in children.
Enlicitide decanoate, also known by its development code MK-0616, is a chemically synthesised substance that comes as a tablet for oral use. It is being developed by Merck & Co. Inc. and has no marketing authorisation in the product records — it remains an investigational substance.
Key points
- Enlicitide decanoate is an oral PCSK9 inhibitor developed by Merck & Co. Inc.
- A Phase 3 trial is testing enlicitide plus rosuvastatin in 975 adults with hyperlipidemia.
- A large Phase 3 cardiovascular outcomes trial plans to enroll 14,755 participants with ASCVD.
- A Phase 2 trial is studying enlicitide with MK-7262 in 750 people with elevated lipoprotein(a).
- A Phase 4 paediatric trial is evaluating enlicitide in 185 children with heterozygous familial hypercholesterolemia.
- All four trials are currently Authorised in the EU Clinical Trials Information System.
What is enlicitide decanoate?
Enlicitide decanoate is a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor. It is a small-molecule chemical substance that is taken by mouth as a tablet. The substance is listed in the EU Clinical Trials Information System under the product name MK-0616.
The US Food and Drug Administration (FDA) approved the medicine under the trade name Lipfendra in 2026 for adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). In the EU product records linked to the trials on this page, however, enlicitide decanoate appears as an investigational substance with no marketing authorisation.
How does enlicitide decanoate work?
Enlicitide decanoate blocks the action of PCSK9, a protein that normally breaks down LDL receptors on the surface of liver cells. When PCSK9 is inhibited, more LDL receptors remain available to remove low-density lipoprotein cholesterol (LDL-C) — often called "bad cholesterol" — from the blood. Reducing LDL-C has been shown in cardiovascular outcomes trials to lower the risk of major adverse cardiovascular events (MACE) in adults at increased risk.
Which conditions is enlicitide decanoate studied for?
- Hyperlipidemia — high levels of fats in the blood, including cholesterol; one Phase 3 trial is testing enlicitide together with rosuvastatin in this condition.
- Atherosclerotic cardiovascular disease (ASCVD) — narrowing of arteries caused by plaque build-up; a large Phase 3 trial is testing whether enlicitide can reduce major cardiovascular events in people at high risk.
- Elevated lipoprotein(a) — high levels of a specific type of cholesterol-carrying particle linked to heart disease; a Phase 2 trial is studying enlicitide together with another investigational medicine, MK-7262.
- Heterozygous familial hypercholesterolemia (HeFH) in children — an inherited condition causing very high cholesterol from birth; a Phase 4 trial is evaluating enlicitide in paediatric patients.
How is enlicitide decanoate given?
Enlicitide decanoate is formulated as a film-coated tablet for oral use. The prescribing information for Lipfendra describes a 20 mg tablet taken once daily on an empty stomach in the morning with water, black coffee, or plain tea. The tablet should be swallowed whole and not split, crushed, or chewed. In the EU registry records, the pharmaceutical form is listed simply as a tablet for oral administration.
What do the clinical trials show?
Four clinical trials of enlicitide decanoate are registered in the EU Clinical Trials Information System, all currently with the status Authorised.–[4]The trials span Phase 2, Phase 3, and Phase 4, reflecting a broad development programme across several cholesterol-related conditions.
The largest trial is a Phase 3 cardiovascular outcomes study in 14,755 participants with atherosclerotic cardiovascular disease. Its primary outcome is the time to first occurrence of a composite of coronary heart disease death, myocardial infarction, ischemic stroke, acute limb ischemia or major amputation, or urgent arterial revascularisation.
A second Phase 3 trial is comparing enlicitide plus rosuvastatin against placebo in 975 adults with hyperlipidemia, measuring the mean percent change in LDL-C from baseline at Week 8.
A Phase 2 trial is studying enlicitide together with MK-7262 in 750 participants with elevated lipoprotein(a). This trial measures percent changes in lipoprotein(a) and LDL-C at Week 8, as well as the number of participants experiencing adverse events.
The fourth trial is a Phase 4 study in 185 children with heterozygous familial hypercholesterolemia. Part A evaluates how the body processes enlicitide (pharmacokinetics), measuring the maximum plasma concentration (Cmax) and the area under the concentration-time curve from 0 to 24 hours (AUC0-24). Part B evaluates the percent change in LDL-C from baseline at Week 24 compared with placebo.
The European Medicines Agency agreed a paediatric investigation plan for enlicitide decanoate in April 2024, covering the treatment of lipid disorders in children. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has also assessed a paediatric investigation plan for the substance in the treatment of lipid disorders.
What side effects are known?
According to the US prescribing information, the frequencies of adverse reactions in adults with hypercholesterolemia were similar between those treated with Lipfendra and those receiving placebo. In a study of adults with heterozygous familial hypercholesterolemia treated with Lipfendra, the most common adverse reactions were diarrhea and dizziness. No contraindications are listed in the prescribing information.