What side effects are associated with this type of intervention?

PCSK9 inhibitors, such as evolocumab and alirocumab, are commonly used to treat atherosclerosis by lowering LDL cholesterol levels. Known side effects of PCSK9 inhibitors include injection site reactions, flu-like symptoms, and muscle pain. Long-term safety data are still being collected, but current evidence suggests that these medications are generally well-tolerated with no compelling evidence linking them to severe adverse events.

What prior FDA approvals exist?

The FDA has approved several PCSK9 inhibitors for the treatment of atherosclerosis by lowering LDL cholesterol levels. Notable drugs include evolocumab (Repatha) and alirocumab (Praluent), both of which have demonstrated the ability to reduce LDL-C by 50-65% when added to statin therapy. These drugs work by preventing the degradation of LDL receptors, thereby enhancing the clearance of LDL cholesterol from the bloodstream. Their safety and efficacy profiles are well-established, making them a promising option for patients with high cardiovascular risk.

What other types of research exist?

Promising alternatives to MK-0616 for treating atherosclerosis include: 1) Evolocumab, which has shown significant reductions in LDL cholesterol and cardiovascular events in multiple trials, including the FOURIER trial. 2) Alirocumab, which has demonstrated efficacy in reducing LDL cholesterol and PAD events, as seen in the ODYSSEY OUTCOMES trial. 3) Inclisiran, a novel siRNA therapy that reduces LDL-C by inhibiting PCSK9 synthesis, with sustained effects shown in the ORION trials.

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Monoclonal Antibodies

MK-0616 for High Cholesterol

Q: What is the mechanism of action of this treatment?

The most common treatments for hardening of the arteries, or atherosclerosis, include statins, ezetimibe, and PCSK9 inhibitors. Statins work by inhibiting the enzyme HMG-CoA reductase, which reduces cholesterol synthesis in the liver, thereby lowering LDL cholesterol levels. Ezetimibe reduces cholesterol absorption in the intestines. PCSK9 inhibitors, such as evolocumab and alirocumab, prevent the degradation of LDL receptors on liver cells, increasing the clearance of LDL cholesterol from the bloodstream. Lowering LDL cholesterol is crucial for atherosclerosis patients because high levels of LDL cholesterol contribute to plaque buildup in the arteries, which can lead to cardiovascular events such as heart attacks and strokes. By effectively reducing LDL cholesterol, these treatments help to slow the progression of atherosclerosis and reduce the risk of serious cardiovascular complications.

Phase 3

Recruiting

Research Sponsored by Merck Sharp & Dohme LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Is treated with moderate- or high-intensity statin (± nonstatin lipid-lowering therapy [LLT]) at Visit 1

Is on a stable dose of all background LLTs for at least 30 days before Visit 1 (Screening) with no medication or dose changes planned during the participation in the study

Must not have

History of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous FH, or double heterozygous FH

History of severe renal insufficiency defined as estimated glomerular filtration rate <30 mL/min/1.73 m2 at Visit 1 (Screening) or has end-stage renal disease on dialysis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date of randomization until the date of first occurrence of 3-point mace, assessed up to approximately 6 years

Awards & highlights

Pivotal Trial

Summary

This trial is testing MK-0616, a pill, in people with high cardiovascular risk. The goal is to see if it can prevent serious heart-related events by lowering bad cholesterol.

Who is the study for?

This trial is for adults at high risk of a major cardiovascular event who have had one before. They must be on stable cholesterol-lowering meds, including statins, and not planning changes during the study. People with very high triglycerides, recent severe heart issues, certain genetic cholesterol disorders, or severe kidney disease can't join.

What is being tested?

The study tests MK-0616, an oral drug aiming to prevent major heart-related events by inhibiting PCSK9 versus a placebo. Participants are randomly assigned to either receive MK-0616 or a placebo to see if it extends the time until another serious heart issue occurs.

What are the potential side effects?

While specific side effects for MK-0616 aren't listed here, PCSK9 inhibitors can cause symptoms like flu-like illness, injection site reactions (though MK-0616 is oral), muscle pain, and possible neurocognitive events.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am currently taking strong cholesterol medication.

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I have been on the same dose of my long-term treatments for over 30 days.

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I am over 18 and have had a major heart or blood vessel event.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a genetic condition that causes very high cholesterol.

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I have severe kidney problems or am on dialysis.

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My heart is very weak, with severe symptoms or recent hospitalization for heart failure.

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I am part of, or plan to join, an LDL cholesterol cleaning program.

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I am scheduled for a procedure to restore blood flow in my arteries.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of randomization until the date of first occurrence of 3-point mace, assessed up to approximately 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of randomization until the date of first occurrence of 3-point mace, assessed up to approximately 6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of randomization until the date of first occurrence of 3-point mace, assessed up to approximately 6 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Time to First Occurrence of Coronary Heart Disease (CHD) Death-Based Major Adverse Cardiovascular Events (MACE)-Plus

Secondary study objectives

Number of Participants Discontinuing from Study Therapy Due to AE

Number of Participants with an Adverse Event (AE)

Percent Change from Baseline in Apolipoprotein B

+13 more

Side effects data

From 2022 Phase 2 trial • 381 Patients • NCT05261126

Dyspepsia

Arthralgia

Fatigue

COVID-19

Nausea

Cholecystitis

Diarrhoea

Deep vein thrombosis

100%

80%

60%

40%

20%

Study treatment Arm

MK-0616 12 mg

MK-0616 18 mg

MK-0616 30 mg

Placebo

MK-0616 6 mg

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Enlicitide DecanoateExperimental Treatment1 Intervention

Participants receive enlicitide decanoate 20 mg once daily.

Group II: PlaceboPlacebo Group1 Intervention

Participants receive placebo once daily.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Enlicitide Decanoate

2024

Completed Phase 2

~450

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for hardening of the arteries, or atherosclerosis, include statins, ezetimibe, and PCSK9 inhibitors. Statins work by inhibiting the enzyme HMG-CoA reductase, which reduces cholesterol synthesis in the liver, thereby lowering LDL cholesterol levels. Ezetimibe reduces cholesterol absorption in the intestines. PCSK9 inhibitors, such as evolocumab and alirocumab, prevent the degradation of LDL receptors on liver cells, increasing the clearance of LDL cholesterol from the bloodstream. Lowering LDL cholesterol is crucial for atherosclerosis patients because high levels of LDL cholesterol contribute to plaque buildup in the arteries, which can lead to cardiovascular events such as heart attacks and strokes. By effectively reducing LDL cholesterol, these treatments help to slow the progression of atherosclerosis and reduce the risk of serious cardiovascular complications.

Evolocumab, a PCSK9-Monoclonal Antibody, Rapidly Reverses Coronary Artery Endothelial Dysfunction in People Living With HIV and People With Dyslipidemia.