Amarin Supports Latest Clinical Research Evaluating VASCEPA® (Icosapent Ethyl) in Patients with Persistent Cardiovascular Risk Presented at ESC Congress 2020, the Annual Meeting of the European Society of Cardiology
September 01, 2020 at 16:30 PM EDT
VASCEPA is the first and only agent studied on top of statin therapy reported to exhibit coronary plaque regression in hypertriglyceridemic patients
VASCEPA in REDUCE-IT® cardiovascular outcomes study achieved statistical significance for primary and secondary endpoints at predefined blinded first and second interim analyses that persisted at final analyses
VASCEPA demonstrated significantly greater benefits in total (first and subsequent) cardiovascular events vs. placebo across studied baseline statin types and prespecified baseline levels of triglycerides, LDL-C, and hsCRP and in patients with or without low HDL-C and elevated triglycerides at baseline
DUBLIN, Ireland and BRIDGEWATER, N.J., Sept. 01, 2020 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN) supported new data, presented at ESC Congress 2020, the annual meeting of the European Society of Cardiology (ESC), held from August 29 - September 1, 2020, adding to the growing body of knowledge on VASCEPA® (icosapent ethyl) in patients at risk for major adverse cardiovascular events.
“Cardiovascular disease continues to impact and challenge us all,” said Craig Granowitz, M.D., Ph.D., Amarin’s senior vice president and chief medical officer. “We see the detrimental effects it has on patients and those who care for them, as well as healthcare systems around the world. Data presented at ESC Congress 2020 provides additional support for potential ways in which VASCEPA can help to alleviate the burden of the worldwide public health crisis that is cardiovascular disease.”
Key data presented at ESC Congress 2020
“Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis in Patients with Elevated Triglycerides on Statin Therapy: Final results of the EVAPORATE Study” – presented on behalf of all authors by Matthew Budoff, M.D., The Lundquist Institute
Highlights: VASCEPA demonstrated significant, 17% regression of low attenuation plaque (LAP) volume on multidetector computed tomography (MDCT) compared with placebo over 18 months.
A total of 80 patients were enrolled in the randomized, double-blind, placebo-controlled EVAPORATE trial. Patients had to have coronary atherosclerosis as documented by MDCT (1 or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels (mean TG at baseline was 259.1 mg/dL [+/- 78.1]). Patients underwent an interim scan at 9 months and a final scan at 18 months. The prespecified primary endpoint was a comparison of change in LAP volume at 18 months between icosapent ethyl and placebo.
Final results showed a significant reduction in the primary endpoint; icosapent ethyl reduced LAP plaque volume by 17% from baseline to the 18-month scan, whereas there was a progression of LAP plaque volume in the placebo group. There were significant differences between icosapent ethyl and placebo at study end for secondary endpoints of other types of plaque volume changes, including and sequentially total, total non-calcified, fibrofatty, and fibrous plaque volumes. All of these forms of coronary plaque regressed in the icosapent ethyl group and progressed in the placebo group, (p<0.01 for all). The only secondary endpoint which did not achieve a significant difference between groups in multivariable modeling was dense calcium (p=0.053). VASCEPA is the first and only agent studied on top of statin therapy reported to exhibit coronary plaque regression in hypertriglyceridemic patients.
“REDUCE-IT: Accumulation of Data Across Prespecified Interim Analyses to Final Results” – presented on behalf of all authors by Brian Olshansky, M.D., University of Iowa
Highlights: The presentation at ESC Congress 2020 was the first presentation of results from the pre-specified interim analyses for the landmark REDUCE-IT® cardiovascular outcomes study. An independent, unblinded DMC (Data and Safety Monitoring Committee) performed interim analyses of data during the REDUCE-IT cardiovascular outcomes study at approximately 60% and 80% (2.9 and 3.7 years of median primary endpoint follow-up, respectively), with a final analysis at 4.9 years median follow-up. Primary and key secondary endpoints were the reduction in the first occurrence of composite of 5-point (cardiovascular death, myocardial infarction [MI], stroke, coronary revascularization or unstable angina) and 3-point (cardiovascular death, MI, stroke) major adverse cardiovascular events (MACE).
Highly statistically significant outcomes were achieved for both primary and key secondary composite endpoints at the first interim, persisted at the second interim, and fully evolved at the final analysis. Consistent, statistically significant outcome measures demonstrating the robust and early benefit of icosapent ethyl were evident for the primary composite endpoint starting at 21 months, and for the key secondary composite endpoint at 25 months. Allowing the REDUCE-IT dataset to mature fully provided physicians and patients with robust, consistent, and reliable efficacy and safety data upon which to base clinical decisions for icosapent ethyl in cardiovascular risk reduction.
“REDUCE-IT: Total Ischemic Events Reduced Across the Full Range of Baseline LDL-Cholesterol and Other Key Subgroups” – presented on behalf of all authors by Deepak L. Bhatt, M.D., M.P.H., Brigham and Women’s Hospital
Highlights: VASCEPA administered at 4 g/day in the REDUCE-IT cardiovascular outcomes study, as previously reported, significantly reduced total ischemic events in statin-treated patients with elevated triglycerides and other cardiovascular risk factors despite well-controlled LDL-C (<100 mg/dL). Presented at ESC Congress 2020 was that, similar to the results of analyses of first occurrences of MACE, reductions in total (first and subsequent) occurrences of MACE were observed across a variety of predefined subgroups, including baseline levels of triglycerides and LDL-C, with substantial reductions across already low LDL-C tertiles in both primary (5-point MACE) and key secondary (3-point MACE) endpoints, as well as in the subgroups with or without elevated hsCRP or low HDL and elevated triglycerides at baseline.
“Are the Results of Clinical Trials Relevant in The Real World? The Applicability of REDUCE-IT to the FAST-MI Registry.” – presented on behalf of all authors by Jean Ferrières, M.D., M.Sc., FESC, Toulouse Rangueil University Hospital
Highlights: In order to evaluate the applicability of results of the REDUCE-IT cardiovascular outcomes study in a French population, the inclusion and exclusion criteria of this landmark study were applied to French patients who were admitted to coronary or intensive care units within 48 hours of symptom onset during a 1-month period (Registry on Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI), 2010 and 2015). The results support that, even in this limited registry of patients, many French patients would qualify for the inclusion criteria of REDUCE-IT in which patients treated with VASCEPA experienced significant reductions in major adverse cardiovascular events.
“REDUCE-IT: Outcomes by Baseline Statin Type” – presented on behalf of all authors by Deepak L. Bhatt, M.D., M.P.H., Brigham and Women’s Hospital
Highlights: The objectives of this analysis were to explore the impact of baseline and concomitant statin type on atherosclerotic cardiovascular disease (ASCVD) outcomes and on LDL-C and ApoB levels in the results of the REDUCE-IT cardiovascular outcomes study. The exploratory analysis examined the primary and key secondary endpoints of REDUCE-IT by individual statin type: atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin, or pitavastatin; and by statin category: lipophilic (i.e., hydrophobic: atorvastatin, simvastatin) vs. lipophobic (i.e., hydrophilic: rosuvastatin, pravastatin). Icosapent ethyl demonstrated similar benefits vs. placebo across all individual baseline statin types and both lipophilic and lipophobic statin categories. Individual baseline statin type and lipophilic/lipophobic category had no meaningful impact on the modest median LDL-C changes from baseline to 1 year and ApoB changes from baseline to 2 years observed with VASCEPA vs. placebo. Primary and key secondary composite endpoint outcomes and changes in LDL-C and ApoB by concomitant statin use yielded similar results. These data provide clinicians with additional insight regarding concomitant statin therapy considerations when prescribing icosapent ethyl and suggest there are important mechanisms of action for the substantial ASCVD risk reduction observed with VASCEPA that are distinct from the LDL-C receptor pathway.
All analyses highlighted above were funded by Amarin.
About Cardiovascular Risk
Controlling bad cholesterol, also known as LDL-C, is one way to reduce a patient’s risk for cardiovascular events, such as heart attack, stroke or death. However, even with the achievement of target LDL-C levels, millions of patients still have significant and persistent risk of cardiovascular events, especially those patients with elevated triglycerides. Statin therapy has been shown to control LDL-C, thereby reducing the risk of cardiovascular events by 25-35%.2 Significant cardiovascular risk remains after statin therapy. People with elevated triglycerides have 35% more cardiovascular events compared to people with normal (in range) triglycerides taking statins.3,4,5
REDUCE-IT, conducted over seven years and completed in 2018, followed 8,179 patients at over 400 clinical sites in 11 countries with the largest number of sites located within the United States. REDUCE-IT was conducted based on a special protocol assessment agreement with FDA. The design of the REDUCE-IT study was published in March 2017 in Clinical Cardiology.6 The primary results of REDUCE-IT were published in The New England Journal of Medicine in November 2018.7 The total events results of REDUCE-IT were published in the Journal of the American College of Cardiology in March 2019.8 These and other publications can be found in the R&D section on the company’s website at www.amarincorp.com.
About VASCEPA® (icosapent ethyl) Capsules
Indications and Limitation of Use
The effect of VASCEPA on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined.
Important Safety Information
Key clinical effects of VASCEPA on major adverse cardiovascular events are included in the Clinical Studies section of the prescribing information for VASCEPA as set forth below:
Effect of VASCEPA on Time to First Occurrence of Cardiovascular Events in Patients with Elevated Triglyceride levels and Other Risk Factors for Cardiovascular Disease in REDUCE-IT
Availability of Other Information About Amarin
1 American Heart Association. Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139–e596.