What side effects are associated with this type of intervention?

Common treatments for high triglycerides include fibrates, omega-3 fatty acids, niacin, and newer therapies like antisense oligonucleotides (e.g., Olezarsen). Fibrates can cause gastrointestinal issues, liver enzyme elevations, and muscle pain. Omega-3 fatty acids are generally well-tolerated but may cause a fishy aftertaste and gastrointestinal discomfort. Niacin can lead to flushing, itching, and liver toxicity at high doses. Antisense oligonucleotides, such as Olezarsen, may cause injection site reactions, flu-like symptoms, and liver enzyme elevations.

What prior FDA approvals exist?

The FDA has approved several treatments for high triglycerides, including fibrates (e.g., fenofibrate), omega-3 fatty acid formulations (e.g., icosapent ethyl), and niacin. Similar to Olezarsen, which is an antisense oligonucleotide targeting apolipoprotein C-III, another antisense oligonucleotide, inotersen, has been approved for treating hereditary transthyretin amyloidosis. While inotersen targets transthyretin, it demonstrates the FDA's recognition of antisense oligonucleotides as a therapeutic class. More broadly, statins and PCSK9 inhibitors are also used to manage lipid levels, though they primarily target LDL cholesterol rather than triglycerides.

What other types of research exist?

Promising alternatives to Olezarsen for high triglycerides include: <ol> <li>Evinacumab: A monoclonal antibody targeting ANGPTL3, shown to significantly reduce triglyceride levels.</li> <li>Inclisiran: An RNA interference therapeutic that lowers LDL-C and has potential benefits for triglyceride reduction.</li> <li>Bempedoic Acid: An ATP citrate lyase inhibitor that can lower LDL-C and may have effects on triglycerides.</li> <li>Volanesorsen: Another antisense oligonucleotide targeting APOC3, similar to Olezarsen, with proven efficacy in reducing triglycerides.</li> </ol>

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Antisense Oligonucleotide

Olezarsen for High Triglycerides and Cardiovascular Disease

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

Common treatments for high triglycerides include lifestyle changes, medications, and novel therapies like antisense oligonucleotides (ASOs). ASOs, such as Olezarsen, work by selectively inhibiting the production of apolipoprotein C-III, a protein that regulates triglyceride metabolism. By reducing apolipoprotein C-III levels, these treatments lower triglyceride levels in the blood, which is crucial for patients with hypertriglyceridemia as it reduces the risk of atherosclerotic cardiovascular disease. Other treatments include fibrates, which activate peroxisome proliferator-activated receptors (PPARs) to increase the breakdown of triglycerides, and omega-3 fatty acids, which reduce triglyceride synthesis in the liver. These mechanisms are important as they help manage and reduce the complications associated with high triglycerides.

Phase 3

Waitlist Available

Research Sponsored by Ionis Pharmaceuticals, Inc.

Eligibility Criteria Checklist

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

Must have

Clinical diagnosis of atherosclerotic cardiovascular disease (ASCVD) or

a. Hypertriglyceridemia with fasting TG ≥200 mg/dL (2.26 millimoles per liter [mmol/L]) and <500 mg/dL (5.65 mmol/L) with either Clinical diagnosis of atherosclerotic cardiovascular disease (ASCVD) or At increased risk for ASCVD

Must not have

Estimated GFR < 30 mL/min/1.73 m^2

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

Summary

This trial is testing olezarsen, a medication that lowers blood triglycerides by blocking a specific protein. It targets patients with high triglycerides and heart disease or severe high triglycerides. The goal is to see if it can help reduce heart disease risk.

Who is the study for?

This trial is for adults with high blood fat levels (triglycerides) and heart disease or at risk of it. They must be on stable heart medications for 4 weeks before joining. People with severe liver issues, very poor kidney function, or uncontrolled diabetes can't participate.

What is being tested?

The study tests Olezarsen's ability to lower fasting triglyceride levels compared to a placebo in patients with high triglycerides and heart disease or those at high risk. It aims to see if Olezarsen is more effective than no treatment.

What are the potential side effects?

Possible side effects of Olezarsen may include reactions at the injection site, changes in liver enzymes, reduced kidney function, low platelet counts, and potential allergic responses.

Eligibility Criteria

Inclusion Criteria

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

Select...

I have been diagnosed with heart disease caused by hardened arteries.

Select...

I have high triglycerides and am at risk for heart disease.

Exclusion Criteria

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

Select...

My kidney function is severely reduced.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

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: OlezarsenExperimental Treatment1 Intervention

Participants will be randomized to receive multiple doses of olezarsen, once every 4 weeks by subcutaneous (SC) injection up to Week 49.

Group II: PlaceboPlacebo Group1 Intervention

Participants will be randomized to receive olezarsen-matching placebo, once every 4 weeks by SC injection up to Week 49.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olezarsen

2022

Completed Phase 3

~1810

0 / 3Eligibility 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

Common treatments for high triglycerides include lifestyle changes, medications, and novel therapies like antisense oligonucleotides (ASOs). ASOs, such as Olezarsen, work by selectively inhibiting the production of apolipoprotein C-III, a protein that regulates triglyceride metabolism. By reducing apolipoprotein C-III levels, these treatments lower triglyceride levels in the blood, which is crucial for patients with hypertriglyceridemia as it reduces the risk of atherosclerotic cardiovascular disease. Other treatments include fibrates, which activate peroxisome proliferator-activated receptors (PPARs) to increase the breakdown of triglycerides, and omega-3 fatty acids, which reduce triglyceride synthesis in the liver. These mechanisms are important as they help manage and reduce the complications associated with high triglycerides.

Antisense therapy and emerging applications for the management of dyslipidemia.Antisense oligonucleotides as therapeutics for hyperlipidaemias.