Olezarsen for Cardiovascular Disease

No longer recruiting at 28 trial locations

Overseen By Ionis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ionis Pharmaceuticals, Inc.

Must be taking: Lipid-lowering medications

Disqualifiers: Diabetes, Stroke, Major surgery, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 53 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called olezarsen, administered as an injection every four weeks. The goal is to determine if it can lower certain blood fats, such as triglycerides, which impact heart health. People with high triglyceride levels who already take medication to lower blood fats and have heart disease or are at risk might be suitable candidates. Participants will receive either olezarsen or a placebo to compare effects over nearly a year. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to continue taking their standard-of-care lipid-lowering medications as per local guidelines.

Is there any evidence suggesting that olezarsen is likely to be safe for humans?

Research has shown that olezarsen has been well-tolerated in past studies. For example, one study found that olezarsen significantly lowered triglycerides, which are fats in the blood, and was generally safe for participants. Interestingly, the group taking a placebo (a harmless pill) reported more side effects than those taking olezarsen, suggesting the treatment's safety. Additionally, olezarsen is already approved in the U.S. for treating familial chylomicronemia syndrome, a rare condition, further supporting its safety for human use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard options for cardiovascular disease, which often include statins and beta-blockers, Olezarsen offers a unique approach by targeting a specific genetic pathway. Researchers are excited about Olezarsen because it works by inhibiting the production of apolipoprotein C-III (ApoC-III), a protein known to elevate triglyceride levels, which is a novel mechanism not utilized by current treatments. This targeted action has the potential to effectively lower triglycerides, reduce cardiovascular risk, and offer benefits over traditional therapies, especially for patients who do not respond well to existing medications. Additionally, Olezarsen is administered through a subcutaneous injection once every four weeks, which could improve compliance compared to daily oral medications.

What evidence suggests that olezarsen might be an effective treatment for cardiovascular disease?

Research has shown that olezarsen, which participants in this trial may receive, can effectively lower triglycerides, fats in the blood linked to heart disease. One study found that olezarsen significantly reduced triglyceride levels compared to a placebo. It also lowered apolipoprotein C-III (apoC-III), a protein that influences fat levels in the blood. Olezarsen has shown promise in reducing harmful blood fats in patients with high triglycerides. This suggests olezarsen could be a helpful treatment for improving heart health by targeting and reducing these fats. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

Inclusion Criteria

Participants must be willing to comply with diet and lifestyle recommendations as able

You have very high levels of triglycerides in your blood when fasting.

Participants must be on standard-of-care (SOC), lipid-lowering medications per local guidelines

Exclusion Criteria

You have been diagnosed with diabetes within the last 12 weeks.

Your HbA1c level is higher than 9.5% at the screening.

You have changed your basal insulin dose by more than 20% in the 3 months before the screening.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive olezarsen or placebo by subcutaneous injection every 4 weeks

53 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

13 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olezarsen

How Is the Trial Designed?

Group I: Olezarsen Experimental Treatment 1 Intervention

Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 49 weeks.

Group II: Placebo Placebo Group 1 Intervention

Olezarsen-matching placebo will be administered once every 4 weeks by SC injection for up to 49 weeks.

Olezarsen is already approved in United States, European Union for the following indications:

Approved in United States as Tryngolza for:

• adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS)

Approved in European Union as Olezarsen for:

• treatment of familial chylomicronemia syndrome

Who Is Running the Clinical Trial?

Ionis Pharmaceuticals, Inc.

Lead Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Published Research Related to This Trial

In a clinical trial involving 114 patients with high triglyceride levels, olezarsen significantly reduced triglyceride levels by up to 60% compared to a 6% increase in the placebo group, demonstrating its efficacy in lowering triglycerides in patients at high risk for cardiovascular disease.

Olezarsen also led to significant reductions in other harmful lipoproteins and showed a good safety profile, with no major adverse effects on liver or kidney function, and only mild injection site reactions reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. Tardif, JC., Karwatowska-Prokopczuk, E., Amour, ES., et al.[2022]

Icosapent ethyl (IPE) has been associated with an increased risk of atrial fibrillation, but it does not significantly raise bleeding risk unless used with antithrombotic medications, indicating a need for careful monitoring in certain patients.

IPE may cause musculoskeletal pain, hepatic disorders, and hyperglycemia, similar to statins, but these risks do not significantly increase when IPE is combined with statins, suggesting it is generally well-tolerated in real-world use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world safety of icosapent ethyl: analysis based on spontaneous reports in FAERS database. Cai, H., Jia, B., Fu, Z., et al.[2023]

Volanesorsen, an antisense drug targeting apoC3 mRNA, significantly reduced levels of apoC-III on various lipoproteins (apoB, Lp(a), and apoA-I) by over 80% compared to placebo in patients with hypertriglyceridemia, indicating its potential efficacy in lowering cardiovascular risk.

The study utilized novel high-throughput ELISAs to measure lipoprotein-associated apoC-III, providing a new method for assessing cardiovascular risk factors and demonstrating that volanesorsen may effectively reduce triglycerides and associated cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results. Yang, X., Lee, SR., Choi, YS., et al.[2021]

Volanesorsen, an antisense oligonucleotide targeting APOC3 mRNA, significantly reduces both apolipoprotein-CIII production and triglyceride levels, making it a promising treatment for severe hypertriglyceridemia.

Current phase 3 trials are evaluating the efficacy and safety of volanesorsen, which could provide a new option for patients at risk of pancreatitis and cardiovascular disease due to high triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of antisense oligonucleotide therapy against apolipoprotein-CIII in hypertriglyceridemia. Gouni-Berthold, I.[2018]

Volanesorsen, an antisense oligonucleotide targeting APOC3 mRNA, has shown strong efficacy in significantly reducing both apoC-III production and triglyceride levels, which are crucial for managing severe hypertriglyceridemia.

Current phase 3 trials are evaluating the safety and effectiveness of volanesorsen, highlighting its potential as a new treatment option for patients at high risk of pancreatitis and cardiovascular disease due to elevated triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APOC-III Antisense Oligonucleotides: A New Option for the Treatment of Hypertriglyceridemia. Schmitz, J., Gouni-Berthold, I.[2019]

Citations

1. ir.ionis.com ir.ionis.com/news-releases/news-release-details/tryngolzatm-olezarsen-approved-us-first-ever-treatment-adults

TRYNGOLZA™ (olezarsen) approved in U.S. as first-ever ... TRYNGOLZA shown to significantly reduce triglycerides and substantially reduce acute pancreatitis events in adults with FCS ; a rare, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05355402

NCT05355402 | A Study of Olezarsen (Formerly Known as ... The purpose of the study is to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo at Months 6 and 12.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8986458/

Apolipoprotein C-III reduction in subjects with moderate ... Olezarsen significantly reduced apoC-III, triglycerides, and atherogenic lipoproteins in patients with moderate hypertriglyceridaemia and at ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/218614Orig1s000IntegratedR.pdf

218614Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov of olezarsen effectiveness to substantiate the results of CS3 and provided supportive safety data. CS8 is a randomized, double-blind ...

5. ir.ionis.com ir.ionis.com/news-releases/news-release-details/ionis-announces-positive-olezarsen-topline-results-phase-3-study

Ionis announces positive olezarsen topline results from ... Olezarsen met the primary endpoint with a statistically significant reduction in triglyceride levels versus placebo; First study to show an ...