What side effects are associated with this type of intervention?

Common treatments for hypertriglyceridemia include fibrates, omega-3 fatty acids, niacin, and statins. Fibrates can cause gastrointestinal issues, gallstones, and muscle pain. Omega-3 fatty acids are generally well-tolerated but may lead to a fishy aftertaste and gastrointestinal discomfort. Niacin can cause flushing, itching, and liver toxicity at high doses. Statins are associated with muscle pain, liver enzyme abnormalities, and a small risk of diabetes. Antisense oligonucleotides like Olezarsen, which target ApoC-III, may have side effects such as injection site reactions, flu-like symptoms, and liver enzyme elevations.

What prior FDA approvals exist?

The FDA has approved several treatments for hypertriglyceridemia, including fibrates (e.g., fenofibrate), omega-3 fatty acid formulations (e.g., icosapent ethyl), and niacin. These treatments primarily work by reducing triglyceride levels through various mechanisms such as increasing lipoprotein lipase activity or decreasing hepatic triglyceride production. While Olezarsen, an antisense oligonucleotide targeting ApoC-III, is still under investigation, it represents a novel approach by directly inhibiting the production of a protein that regulates triglyceride metabolism. Similar investigational therapies include mipomersen, an antisense oligonucleotide targeting apoB, which is in phase 3 trials for lowering lipoprotein(a) and potentially triglycerides.

What other types of research exist?

Promising alternatives to Olezarsen for hypertriglyceridemia include PCSK9 inhibitors like evolocumab and alirocumab, which have shown efficacy in lowering LDL cholesterol and may have effects on triglycerides. Additionally, CETP inhibitors such as TA-8995 have demonstrated significant lipid-lowering effects. Investigational agents like inclisiran, an siRNA targeting PCSK9, also show potential for lipid management. These alternatives should be discussed with a healthcare provider to determine the best treatment plan.

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Antisense Oligonucleotide

Olezarsen for High Triglycerides

Phase 3

Recruiting

Research Sponsored by Ionis Pharmaceuticals, Inc.

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a medication called olezarsen to see if it is safe and can be tolerated by people with very high levels of blood fat (triglycerides). The study involves up to 700 participants who will take the medication for several months. The goal is to help reduce the fat in their blood and prevent serious health issues. Olezarsen significantly reduced apoC-III, triglycerides, and atherogenic lipoproteins in patients with moderate hypertriglyceridaemia and at high risk for or with established cardiovascular disease.

Who is the study for?

This trial is for people with severe hypertriglyceridemia who are already on a stable regimen of lipid-lowering therapy. Participants should have completed previous olezarsen studies (ISIS 678354-CS5 or CS6) without serious issues. Those with new or worsening conditions that could affect study participation, or who need disallowed medications, can't join.

What is being tested?

The trial is testing the safety and tolerability of a drug called Olezarsen when given by injection to patients with very high triglyceride levels in their blood. The goal is to see how well participants handle the medication over time.

What are the potential side effects?

While specific side effects aren't listed here, generally speaking, drugs like Olezarsen may cause reactions at the injection site, liver problems, changes in fat levels in blood other than triglycerides, and possible interactions with other medications.

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

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: OlezarsenExperimental Treatment1 Intervention

Participants who completed either ISIS 678354-CS5 (NCT05079919) or ISIS 678354-CS6 (NCT05552326) study would be enrolled to receive olezarsen, subcutaneous (SC) injection, once every 4 weeks from Week 1 through Week 49.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olezarsen

2022

Completed Phase 3

~1810

Do I qualify?Apply below to find out

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 hypertriglyceridemia include lifestyle modifications, fibrates, omega-3 fatty acids, and newer therapies like antisense oligonucleotides. Olezarsen, an antisense oligonucleotide, targets and reduces the production of apolipoprotein C-III (ApoC-III), a protein that inhibits the breakdown of triglycerides. By lowering ApoC-III levels, Olezarsen enhances triglyceride clearance from the bloodstream, significantly reducing triglyceride levels. This is crucial for hypertriglyceridemia patients as high triglyceride levels are associated with an increased risk of pancreatitis and cardiovascular disease. Other treatments, such as fibrates, activate peroxisome proliferator-activated receptors (PPARs) to increase lipid metabolism, while omega-3 fatty acids reduce hepatic triglyceride synthesis. These mechanisms collectively help manage and lower triglyceride levels, improving patient outcomes.