What side effects are associated with this type of intervention?

PCSK9 inhibitors, such as evolocumab and alirocumab, are commonly used treatments for cardiovascular disease. The most frequently reported side effects include mild local injection site reactions like erythema, pain, or bruising. Serious adverse effects are uncommon, but hypersensitivity reactions such as rash, pruritus, and urticaria have been noted. Rarely, severe allergic reactions like nummular eczema and hypersensitivity vasculitis can occur. Neurocognitive symptoms have been reported in less than 1% of patients, but no significant evidence of neurocognitive impairment was found in larger studies. Muscle toxicity and elevated liver enzymes are not typically associated with PCSK9 inhibitors.

What prior FDA approvals exist?

The FDA has approved several PCSK9 inhibitors for the treatment of cardiovascular disease, particularly for lowering LDL cholesterol. Notable drugs include Alirocumab and Evolocumab, which are monoclonal antibodies that inhibit PCSK9, leading to significant reductions in LDL-C levels and improved cardiovascular outcomes. These drugs have been shown to reduce the risk of major cardiovascular events such as heart attacks and strokes. Inclisiran, currently being studied, uses siRNA to inhibit PCSK9, offering a novel approach to LDL-C reduction with potentially less frequent dosing.

What other types of research exist?

Promising alternatives to Inclisiran for cardiovascular disease patients include Evolocumab and Alirocumab, which are monoclonal antibodies that inhibit PCSK9. Additionally, Evinacumab, an ANGPTL3 inhibitor, has shown efficacy in reducing LDL cholesterol levels. These therapies offer different mechanisms of action and have demonstrated significant cardiovascular benefits in clinical studies.

← Back to Search

RNA-based Therapeutic

Inclisiran for Cardiovascular Disease (ORION-4 Trial)

Phase 3

Waitlist Available

Led By Marion Mafham

Research Sponsored by University of Oxford

Eligibility Criteria Checklist

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

Must have

You have been diagnosed with Hypercholesterolemia

Have you at least 4 weeks of been taking statins

Must not have

Acute coronary syndrome or stroke less than 4 weeks before the Screening visit or during the Run-in period

Coronary revascularization procedure planned within the next 6 months

Timeline

Screening 15 days

Treatment 84 months

Follow Up 1 day

Awards & highlights

Pivotal Trial

Summary

This trial tests inclisiran, a new injection to lower cholesterol, in people who have had heart attacks, strokes, or surgeries for blocked arteries. It works by blocking a protein that produces bad cholesterol.

Who is the study for?

This trial is for men over 40 and women over 55 with a history of heart attack, stroke, or procedures for blocked arteries. It's not open to those planning heart surgery soon, with chronic liver disease, on dialysis/transplantation, pregnant/breastfeeding women, or anyone with severe illnesses that could interfere with the study.

What is being tested?

ORION-4 is testing whether inclisiran injections can reduce the risk of heart attacks and strokes in people who've already had cardiovascular events. Participants will be randomly assigned to receive either inclisiran or a placebo.

What are the potential side effects?

While specific side effects of inclisiran are not listed here, common ones may include injection site reactions, allergic responses, flu-like symptoms, nausea and potential interactions with other drugs.

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

Select...

I have not had a heart attack or stroke in the last 4 weeks.

Select...

I am scheduled for a heart artery procedure in the next 6 months.

Select...

I have a long-term liver condition.

Select...

I have previously used inclisiran or been in a study for it.

Timeline

Screening ~ 15 days1 visit

Treatment ~ 84 months12 visits

Follow Up ~ 1 day0 visits

Screening ~ 15 days

Treatment ~ 84 months

Follow Up ~1 day

This trial's timeline: 15 days for screening, 84 months for treatment, and 1 day for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Number of participants with a major adverse cardiovascular event (MACE)

Secondary study objectives

Number of participants with MACE among those recorded to be taking high-intensity statin at baseline

Number of participants with a composite of CHD death or myocardial infarction

Number of participants with cardiovascular death

Side effects data

From 2019 Phase 3 trial • 482 Patients • NCT03397121

12%

Nasopharyngitis

Injection site reaction

Upper respiratory tract infection

Back pain

Influenza

Acute myocardial infarction

Aortic valve stenosis

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Inclisiran

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: InclisiranExperimental Treatment1 Intervention

Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection at randomization, 3 months and then every 6 months.

Group II: PlaceboPlacebo Group1 Intervention

Placebo will be administered as SC injections of saline solution at randomization, 3 months and then every 6 months.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Inclisiran

2021

Completed Phase 3

~2650

0 / 6Eligibility 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

Cardiovascular Disease (CVD) treatments often target lowering low-density lipoprotein cholesterol (LDL-C), a key risk factor for heart attacks and strokes. Statins work by inhibiting HMG-CoA reductase, an enzyme involved in cholesterol synthesis, thereby reducing LDL-C levels. Ezetimibe decreases cholesterol absorption in the intestines, providing an additional LDL-C lowering effect. PCSK9 inhibitors, such as Inclisiran, work by inhibiting the PCSK9 protein, which leads to increased recycling of LDL receptors and enhanced clearance of LDL-C from the bloodstream. This is particularly important for CVD patients as lower LDL-C levels are associated with reduced risk of adverse cardiovascular events, such as heart attacks and strokes.