Amarin Highlights Key Data Providing Mechanistic Insights Into Eicosapentaenoic Acid At ACC.24

Author: Benzinga Newsdesk | April 08, 2024 08:23am

Amarin Corporation plc (NASDAQ:AMRN) today highlighted three data presentations at ACC.24 showcasing the mechanistic activity of Eicosapentaenoic acid (EPA), including the potential effects of EPA on endothelial cell dysfunction and on oxidation of samples enriched with Lp(a).

 

"The data presented at ACC.24 provide new evidence surrounding the mechanism of action for VASCEPA/VAZKEPA, including the effect of the compound in combination with high-intensity statin on endothelial cell function during inflammation and the compound's effect on Lp(a) levels," said R. Preston Mason, Ph.D., Brigham and Women's Hospital. "These learnings further advance understanding of how EPA and VASCEPA/VAZKEPA work to reduce cardiovascular events in at-risk patients."

The studies and their key findings are outlined below:

Eicosapentaenoic acid (EPA) and a High Intensity Statin Enhanced Expression of Proteins for Detoxification of Reactive Oxygen Species during Angiotensin II Challenge in Endothelial Cells

This analysis measured the separate and combined effects of EPA and rosuvastatin on expression of proteins involved in detoxification in vascular endothelial cells under inflammatory conditions with angiotensin II  (Ang II).

The combination of EPA and rosuvastatin favorably modulated the expression of proteins related to oxidative stress and detoxification under disease-like conditions. These findings indicate that the net benefits of a high intensity statin and EPA, compared to statin alone, on expression of detoxification proteins during inflammation may contribute to reduced atherothrombotic risk in outcome trials.

Eicosapentaenoic Acid (EPA) and Rosuvastatin Modulate Expression of Endothelial Proteins that Regulate Function and Platelet Activity during Angiotensin II Stimulation 

In this analysis, investigators compared the separate and combined effects of EPA and rosuvastatin on expression of proteins that regulate platelet signaling and nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs) subjected to angiotensin II (Ang II) stimulus.

The combination of EPA and rosuvastatin favorably modulated proteins involved in platelet degranulation and NO bioavailability in HUVECs under inflammatory conditions to a greater extent than their separate treatments. The beneficial effects of a high intensity statin and EPA on endothelial dysfunction may contribute to reduced atherothrombotic risk in outcome trials.

Eicosapentaenoic Acid (EPA) Inhibits Lipoprotein(a) [Lp(a)] Oxidation due to Scavenging Mechanisms In Vitro

Elevated Lp(a) levels are an independent and causal risk factor for cardiovascular (CV) disease with limited treatments available. Oxidized Lp(a) stimulates foam cell formation, endothelial dysfunction, and inflammation. ​

In this analysis, investigators tested EPA effects on oxidation of samples enriched with Lp(a) compared to the fully saturated eicosaenoic acid (EA; 20:0) and Trolox, a water-soluble analog of Vitamin E.

Investigators found that EPA inhibited oxidation of Lp(a) enriched plasma in a time-dependent fashion consistent with a free radical scavenging mechanism. The potent antioxidant actions of EPA may contribute to reduced CV events in REDUCE-IT, including among those subjects with elevated Lp(a).

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