Investigational drug vupanorsen reduces non-HDL cholesterol by up to 28%

In a study presented at the American College of Cardiology 71st Annual scientific session. Additionally, vupanorsen reduced triglyceride levels by up to 57% and levels of angiopoietin-like 3 (ANGPTL3), the protein the drug was designed to target, by up to 95%. The drug had more modest effects on low-density lipoprotein (LDL) and apolipoprotein B (ApoB) cholesterol levels.

High levels of non-HDL cholesterol in the blood are associated with a high risk of cardiovascular disease. This risk can be reduced by cholesterol-lowering drugs such as statins. However, the researchers said there is an unmet need for additional cholesterol-lowering strategies for patients who still have high cholesterol after taking statins.

Vupanorsen reduced non-HDL cholesterol at all doses studied statistically significantly and reduced triglyceride levels by half. Whether these reductions would be sufficient to translate into a clinically meaningful reduction in cardiovascular risk remains unclear. »

Brian Bergmark, MD, cardiologist at Brigham and Women’s Hospital, thrombolysis in myocardial infarction (TIMI) study group investigator, and lead study author

Vupanorsen is an investigational drug designed to lower non-HDL cholesterol by reducing the production of ANGPTL3, a protein that inhibits enzymes involved in triglyceride and cholesterol metabolism. For the trial, the researchers recruited 286 patients from 55 medical centers in the United States, Canada and Poland. Prior to the study, participants had non-HDL cholesterol of 100 mg/dL or higher, triglycerides of 150 to 500 mg/dL, and were already taking a statin.

Participants were randomly assigned to receive either a placebo or one of seven doses of vupanorsen ranging from 80 milligrams once a month to 160 milligrams every two weeks by subcutaneous injection. At 24 weeks, people taking vupanorsen had a significant reduction in non-HDL cholesterol, on average, reaching the study’s primary endpoint. Additionally, patients taking vupanorsen had a 41.3% to 56.8% reduction in triglycerides, a reduction in low-density lipoprotein (LDL) cholesterol by up to 16.2%, and a reduction in apolipoprotein B (ApoB) up to 15.1%. ANGPTL3 levels were reduced by 69.9% to 95.2% in those taking vupanorsen.

Participants taking vupanorsen at higher doses experienced an increased rate of injection site reactions and elevations in liver enzymes. Additionally, the researchers found that vupanorsen use was associated with dose-related increases in fat accumulation in the liver. This was unexpected, as results from laboratory studies in animal models suggested that the drug could potentially help reduce fat content in the liver.

“Regardless of the future of this compound, we found information that could be very relevant for future studies,” Bergmark said. “There are many other compounds targeting this pathway or adjacent metabolic pathways through similar mechanisms, and it will be interesting to see how this plays out for other agents.”

Bergmark said it’s unclear whether the drug might have greater benefits for people with particular lipid disorders that lead to extremely high levels of non-HDL cholesterol. He added that a larger sample size could potentially shed more light on how the drug works to lower cholesterol.

This study was simultaneously published online in Traffic at the time of presentation. The study was funded by Pfizer.

Bergmark will be available to the media at a press conference on Sunday, April 3 at 9:30 a.m. ET / 1:30 p.m. UTC in room 103AB.

Bergmark will present the study, “Effect of Vupanorsen on Non-High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients with Elevated Cholesterol – TRANSLATE-TIMI 70,” on Sunday, April 3 at 8:00 a.m. ET / 12:00 p.m. UTC in the main tent, Hall D.


American College of Cardiology

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