What is the mechanism of action of this treatment?

Common treatments for hypertriglyceridemia include fibrates, omega-3 fatty acids, niacin, and statins. Fibrates activate peroxisome proliferator-activated receptors (PPARs), which increase the oxidation of fatty acids and reduce triglyceride levels. Omega-3 fatty acids reduce hepatic triglyceride synthesis and increase triglyceride clearance. Niacin inhibits the release of free fatty acids from adipose tissue, reducing hepatic triglyceride production. Statins primarily lower LDL cholesterol but also have modest triglyceride-lowering effects. Olezarsen, an antisense oligonucleotide targeting ApoC-III, reduces triglyceride levels by inhibiting the production of ApoC-III, a protein that inhibits lipoprotein lipase and hepatic uptake of triglyceride-rich particles. These mechanisms are crucial for hypertriglyceridemia patients as they help reduce the risk of pancreatitis and cardiovascular disease by lowering elevated triglyceride levels.

What side effects are associated with this type of intervention?

Common treatments for hypertriglyceridemia include fibrates, omega-3 fatty acids, niacin, and newer agents like antisense oligonucleotides targeting ApoC-III, such as Olezarsen. Fibrates can cause gastrointestinal issues, liver enzyme elevations, 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. Antisense oligonucleotides like 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 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 different mechanisms. While Olezarsen is an antisense oligonucleotide targeting ApoC-III, another similar approach in development is mipomersen, an antisense therapy targeting apoB messenger RNA, which is currently in phase 3 trials. These therapies represent a newer class of treatments aimed at reducing triglyceride levels by inhibiting specific proteins involved in lipid metabolism.

What other types of research exist?

Promising novel alternatives to Olezarsen for hypertriglyceridemia patients include PCSK9 inhibitors (e.g., inclisiran) and mTOR inhibitors (e.g., temsirolimus). PCSK9 inhibitors have shown significant efficacy in lowering LDL-C, which can indirectly affect triglyceride levels. mTOR inhibitors, while primarily used in cancer treatment, have shown potential in metabolic regulation and lipid metabolism.

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Antisense Oligonucleotide

Olezarsen for High Triglycerides

Verified Trial

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

Must not have

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up month 6 and month 12

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new medication called olezarsen to see if it can lower blood fat levels in people with high triglycerides. The goal is to find out if olezarsen can effectively reduce triglycerides and help prevent related health issues. Olezarsen has been shown to significantly reduce 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, having fasting triglycerides of 500 mg/dL or higher. Participants should be on a stable lipid-lowering therapy for at least 4 weeks and willing to follow diet and lifestyle advice. Those with certain liver, kidney, or blood sugar conditions are excluded.

What is being tested?

The study tests the effectiveness of Olezarsen in reducing fasting triglyceride levels compared to a placebo. Participants will receive either Olezarsen or a placebo injection and their change in triglyceride levels from the start of the study will be measured.

What are the potential side effects?

While specific side effects for Olezarsen aren't provided here, similar medications can cause reactions at the injection site, liver enzyme changes, potential kidney issues, and may affect blood sugar control.

Eligibility Criteria

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 ~ month 6 and month 12

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~month 6 and month 12

This trial's timeline: 3 weeks for screening, Varies for treatment, and month 6 and month 12 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Percent Change from Baseline in Fasting TG at 6 Months (Average of Weeks 25 and 27) Compared to Placebo

Secondary study objectives

Acute Pancreatitis Event Rate from Week 13 to Week 53 Compared to Placebo, in Participants with ≥ 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment

Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo

Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo, in Participants with ≥ 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment

+9 more

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

Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.

Group II: PlaceboPlacebo Group1 Intervention

Olezarsen-matching placebo will be administered once every 4 weeks by subcutaneous (SC) injection 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

0 / 1Eligibility 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 hypertriglyceridemia include fibrates, omega-3 fatty acids, niacin, and statins. Fibrates activate peroxisome proliferator-activated receptors (PPARs), which increase the oxidation of fatty acids and reduce triglyceride levels. Omega-3 fatty acids reduce hepatic triglyceride synthesis and increase triglyceride clearance. Niacin inhibits the release of free fatty acids from adipose tissue, reducing hepatic triglyceride production. Statins primarily lower LDL cholesterol but also have modest triglyceride-lowering effects. Olezarsen, an antisense oligonucleotide targeting ApoC-III, reduces triglyceride levels by inhibiting the production of ApoC-III, a protein that inhibits lipoprotein lipase and hepatic uptake of triglyceride-rich particles. These mechanisms are crucial for hypertriglyceridemia patients as they help reduce the risk of pancreatitis and cardiovascular disease by lowering elevated triglyceride levels.