09.25.18
Topline results of REDUCE-IT, a cardiovascular (CV) outcomes trial examining Amarin Corporations’ Vascepa prescription omega-3 product, were released.
Vascepa (icosapent ethyl) is a single-molecule prescription product consisting of omega-3 eicosapentaenoic acid (EPA) in ethyl-ester form. Vascepa is not fish oil, according to Amarin, but is derived from fish through a manufacturing process designed to eliminate impurities and isolate the single molecule active ingredient. Vascepa, known in scientific literature as AMR101, has been designated a new chemical entity by the U.S. Food and Drug Administration (FDA).
The Reduction of Cardiovascular Events with EPA​ ​Intervention Trial​ (REDUCE-IT) evaluated 8,179 statin-treated adults globally with elevated CV risk. Enrolled participants had LDL cholesterol (LDL-C) between 41-100 mg/dL (median baseline LDL-C 75 mg/dL) controlled by statin therapy. Patients also had various cardiovascular risk factors including persistent elevated triglycerides (TGs) between 150-499 mg/dL (median baseline 216 mg/dL), and either established cardiovascular disease (secondary prevention cohort) or diabetes mellitus and at least one other CV risk factor (primary prevention cohort). The intent-to-treat patient population was given 4 grams/day of Vascepa, or placebo.
Results demonstrated that REDUCE-IT met its primary endpoint showing approximately 25% relative risk reduction, to a high degree of statistical significance (p<0.001), in major adverse CV events (MACE) such as cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization.
The study also found Vascepa was well tolerated with a safety profile consistent with clinical experience associated with omega-3 fatty acids and current FDA-approved labeling. The proportions of patients experiencing adverse events and serious adverse events in REDUCE-IT were similar between the active and placebo treatment groups.
While these results have yet to be published, Amarin said it is eager to share REDUCE-IT data in greater detail with both the medical community and regulatory authorities. REDUCE-IT results have been accepted for presentation at the 2018 Scientific Sessions of the American Heart Association (AHA) on Nov. 10, 2018 in Chicago, IL.
"I look forward to the publication of these detailed REDUCE-IT results in a major peer-reviewed journal and to presenting them at the AHA in November," stated Deepak L. Bhatt, MD, MPH, Professor of Medicine at Harvard Medical School, executive director of Interventional Cardiovascular Programs in the Heart and Vascular Center at Brigham and Women's Hospital, and the Principal Investigator and Steering Committee Chair for REDUCE-IT.
"We are delighted with these topline study results," said John F. Thero, president and CEO of Amarin. "Given Vascepa is affordably priced, orally administered and has a favorable safety profile, REDUCE-IT results could lead to a new paradigm in treatment to further reduce the significant cardiovascular risk that remains in millions of patients with LDL-C controlled by statin therapy, as studied in REDUCE-IT."
Craig Granowitz, MD, PhD, senior vice president and chief medical officer of Amarin suggested the findings of this trial are specific and unique to the Vascepa EPA formula. "Considered against the backdrop of multiple unsuccessful cardiovascular outcomes studies of earlier generation drug therapies, including multiple recent failed cardiovascular studies of omega-3 mixture products that contain the omega-3 acid DHA, REDUCE-IT topline results stand alone as positive and confirm our hypothesis that pure EPA Vascepa at 4 grams/day can provide additional cardiovascular risk reduction benefit on top of LDL-C control with standard of care statin therapy in studied patients," he said. "REDUCE-IT results cannot be generalized to fenofibrate, fish oil or omega-3 mixture products that contain DHA. The most relevant comparator study to REDUCE-IT is the Japan EPA lipid intervention study (JELIS), the 18,645 patient, open label, blinded endpoint outcomes study of EPA added to low-dose statin therapy, which showed cardiovascular event reduction in Japanese hypercholesterolemic patients of 19% in the overall population and 53% in a subgroup of patients with elevated TG levels and low HDL-C [Yokoyama M, Origasa H, Matsuzaki M, et al. Lancet, 2007; Saito Y, Yokoyama M, Origasa H, et al. Atherosclerosis, 2008; Matsuzaki M, Yokoyama M, Saito Y, et al. Circ J. 2009].”
Commenting on the study’s initial findings, Ellen Schutt, executive director of the Global Organization for EPA and DHA Omega-3s (GOED), said: “GOED was pleased to see the results of the REDUCE-IT study, as it supports the body of evidence showing the benefits of omega-3s for cardiovascular outcomes. We are interested to hear more about the nuances of their research—as well as the upcoming VITAL study—when they are both presented in November at the American Heart Association conference.”
Vascepa (icosapent ethyl) is a single-molecule prescription product consisting of omega-3 eicosapentaenoic acid (EPA) in ethyl-ester form. Vascepa is not fish oil, according to Amarin, but is derived from fish through a manufacturing process designed to eliminate impurities and isolate the single molecule active ingredient. Vascepa, known in scientific literature as AMR101, has been designated a new chemical entity by the U.S. Food and Drug Administration (FDA).
The Reduction of Cardiovascular Events with EPA​ ​Intervention Trial​ (REDUCE-IT) evaluated 8,179 statin-treated adults globally with elevated CV risk. Enrolled participants had LDL cholesterol (LDL-C) between 41-100 mg/dL (median baseline LDL-C 75 mg/dL) controlled by statin therapy. Patients also had various cardiovascular risk factors including persistent elevated triglycerides (TGs) between 150-499 mg/dL (median baseline 216 mg/dL), and either established cardiovascular disease (secondary prevention cohort) or diabetes mellitus and at least one other CV risk factor (primary prevention cohort). The intent-to-treat patient population was given 4 grams/day of Vascepa, or placebo.
Results demonstrated that REDUCE-IT met its primary endpoint showing approximately 25% relative risk reduction, to a high degree of statistical significance (p<0.001), in major adverse CV events (MACE) such as cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization.
The study also found Vascepa was well tolerated with a safety profile consistent with clinical experience associated with omega-3 fatty acids and current FDA-approved labeling. The proportions of patients experiencing adverse events and serious adverse events in REDUCE-IT were similar between the active and placebo treatment groups.
While these results have yet to be published, Amarin said it is eager to share REDUCE-IT data in greater detail with both the medical community and regulatory authorities. REDUCE-IT results have been accepted for presentation at the 2018 Scientific Sessions of the American Heart Association (AHA) on Nov. 10, 2018 in Chicago, IL.
"I look forward to the publication of these detailed REDUCE-IT results in a major peer-reviewed journal and to presenting them at the AHA in November," stated Deepak L. Bhatt, MD, MPH, Professor of Medicine at Harvard Medical School, executive director of Interventional Cardiovascular Programs in the Heart and Vascular Center at Brigham and Women's Hospital, and the Principal Investigator and Steering Committee Chair for REDUCE-IT.
"We are delighted with these topline study results," said John F. Thero, president and CEO of Amarin. "Given Vascepa is affordably priced, orally administered and has a favorable safety profile, REDUCE-IT results could lead to a new paradigm in treatment to further reduce the significant cardiovascular risk that remains in millions of patients with LDL-C controlled by statin therapy, as studied in REDUCE-IT."
Craig Granowitz, MD, PhD, senior vice president and chief medical officer of Amarin suggested the findings of this trial are specific and unique to the Vascepa EPA formula. "Considered against the backdrop of multiple unsuccessful cardiovascular outcomes studies of earlier generation drug therapies, including multiple recent failed cardiovascular studies of omega-3 mixture products that contain the omega-3 acid DHA, REDUCE-IT topline results stand alone as positive and confirm our hypothesis that pure EPA Vascepa at 4 grams/day can provide additional cardiovascular risk reduction benefit on top of LDL-C control with standard of care statin therapy in studied patients," he said. "REDUCE-IT results cannot be generalized to fenofibrate, fish oil or omega-3 mixture products that contain DHA. The most relevant comparator study to REDUCE-IT is the Japan EPA lipid intervention study (JELIS), the 18,645 patient, open label, blinded endpoint outcomes study of EPA added to low-dose statin therapy, which showed cardiovascular event reduction in Japanese hypercholesterolemic patients of 19% in the overall population and 53% in a subgroup of patients with elevated TG levels and low HDL-C [Yokoyama M, Origasa H, Matsuzaki M, et al. Lancet, 2007; Saito Y, Yokoyama M, Origasa H, et al. Atherosclerosis, 2008; Matsuzaki M, Yokoyama M, Saito Y, et al. Circ J. 2009].”
Commenting on the study’s initial findings, Ellen Schutt, executive director of the Global Organization for EPA and DHA Omega-3s (GOED), said: “GOED was pleased to see the results of the REDUCE-IT study, as it supports the body of evidence showing the benefits of omega-3s for cardiovascular outcomes. We are interested to hear more about the nuances of their research—as well as the upcoming VITAL study—when they are both presented in November at the American Heart Association conference.”
