Vascepa® (icosapent ethyl) 26% Reduction in Key Secondary Composite Endpoint of Cardiovascular Death, Heart Attacks and Stroke Demonstrated in REDUCE-IT™ Supports 25% Overall Reduction in Five-Point Major Adverse Cardiovascular Event Primary Composite E
Landmark Cardiovascular Risk Reduction Benefits Demonstrated in REDUCE-IT Are Largest of Any Major Cardiovascular Outcomes Study of a Drug Intended to Address Residual Cardiovascular Risk Remaining After Cholesterol Management
Cardiovascular Death Reduced by 20%
Fatal or Nonfatal Heart Attacks Reduced by 31%
Fatal or Nonfatal Stroke Reduced by 28%
Urgent or Emergent Coronary RevascularizationReduced by 35%
Hospitalization for Unstable AnginaReduced by 32%
Number Needed to Treat for Primary Composite Endpoint: 21
Patient Years of Study Support Favorable Benefit/Risk Profile in REDUCE-IT
Affordably Priced Vascepa Positions Amarin with Potential to Help Millions of Patients
Conference Call Scheduled for Today,
Cardiovascular benefits appeared not to be influenced significantly by triglyceride (TG) levels at baseline (135 mg/dL to 499 mg/dL baseline range) or as achieved at one year, suggesting mechanisms at work with use of Vascepa that are independent of triglyceride reduction. Results were robust across multiple subgroups, including in patients with and without diabetes at baseline. REDUCE-IT study results were simultaneously published in
REDUCE-IT was a global study of 8,179 statin-treated adults with elevated CV risk. Many patients with well-managed LDL-C remain at high risk for cardiovascular events. No therapy is currently approved to treat the residual risk in REDUCE-IT patients and no other therapy has demonstrated a 25% risk reduction on top of statin therapy in a major cardiovascular outcomes trial. REDUCE-IT studied Vascepa 4 grams/day as compared to placebo over a median follow-up time of 4.9 years.
Efficacy results for Vascepa as presented today from REDUCE-IT are as follows:
Primary endpoint achieved: 25% relative risk reduction (RRR) (hazard ratio (HR), 0.75; 95% confidence interval CI, 0.68-0.83; p<0.001) in first occurrence of major adverse CV events (MACE) in the intent-to-treat population consisting of a composite of cardiovascular death, nonfatal myocardial infarction (MI or heart attack), nonfatal stroke, coronary revascularization (procedures such as stents and by-pass) and unstable angina requiring hospitalization.
- Number needed to treat (NNT) was 21 for the first occurrence of MACE in the 5-point primary composite endpoint.
- For perspective, NNTs for cholesterol-managing drugs atorvastatin (Lipitor®)1 and evolocumab (Repatha®)2 were reported to be 45 and 67, respectively. These drugs are not competitors with Vascepa as Vascepa is not a therapy for cholesterol (LDL-C) management nor has Vascepa been evaluated in a head-to-head study with these drugs.
Key secondary endpoint achieved: 26% RRR (HR, 0.74; 95% CI, 0.65-0.83; p<0.001) in 3-point MACE in the intent-to-treat population consisting of a composite of cardiovascular death, nonfatal heart attack and nonfatal stroke.
Additional secondary endpoints achieved: Seven secondary endpoints were achieved below the key secondary endpoint, as follows (in order of sequential statistical testing within the prespecified hierarchy):
- Cardiovascular death or nonfatal heart attack: 25% RRR (HR, 0.75; 95% CI, 0.66-0.86; p<0.001)
- Fatal or nonfatal heart attack: 31% RRR (HR, 0.69; 95% CI, 0.58-0.81; p<0.001)
- Urgent or emergent revascularization: 35% RRR (HR, 0.65; 95% CI, 0.55-0.78; p<0.001)
- Cardiovascular death: 20% RRR (HR, 0.80; 95% CI, 0.66-0.98; p=0.03)
- Hospitalization for unstable angina: 32% RRR (HR, 0.68; 95% CI, 0.53-0.87; p=0.002)
- Fatal or nonfatal stroke: 28% RRR (HR, 0.72; 95% CI, 0.55-0.93; p=0.01)
- Total mortality, nonfatal heart attack or nonfatal stroke: 23% RRR (HR, 0.77; 95% CI, 0.69-0.86; p<0.001)
The next prespecified secondary endpoint in the hierarchy, and the only such endpoint that did not achieve statistical significance, is as follows:
- Total mortality, which includes mortality from non-cardiovascular and cardiovascular events: 13% RRR (HR, 0.87; 95% CI, 0.74-1.02; p=0.09)
Baseline demographics: Patients qualified to enroll in REDUCE-IT had LDL-C between 41-100 mg/dL (median baseline LDL-C 75 mg/dL) controlled by statin therapy and various cardiovascular risk factors including persistent elevated triglycerides (TGs) between 135-499 mg/dL (median baseline 216 mg/dL) and either established cardiovascular disease (secondary prevention cohort) or age 50 or more with diabetes mellitus and at least one other CV risk factor (primary prevention cohort). Approximately 59% of the patients had diabetes at baseline and approximately 71% of the patients had established cardiovascular disease at time of enrollment.
Safety: Excluding the major adverse CV events (MACE) results described above, overall adverse event rates in REDUCE-IT were similar across the statin plus Vascepa and the statin plus placebo treatment groups. There were no significant differences between treatments in the overall rate of treatment emergent adverse events or serious adverse events leading to withdrawal of study drug. The one serious adverse event occurring at a frequency of >2% was pneumonia which occurred at a numerically higher rate in the statin plus placebo treatment group (2.9%) than in the statin plus Vascepa treatment group (2.6%). Adverse events occurring in 5% or greater of patients and more frequently with Vascepa than placebo were peripheral edema (6.5% Vascepa patients versus 5.0% placebo patients), constipation (5.4% Vascepa patients versus 3.6% placebo patients), and atrial fibrillation (5.3% Vascepa patients versus 3.9% placebo patients). There were numerically more serious adverse events related to bleeding in the statin plus Vascepa treatment group although overall rates were low with no fatal bleeding observed in either group and no significant difference in adjudicated hemorrhagic stroke or serious central nervous system or gastrointestinal bleeding events between treatments. In summary, Vascepa was well tolerated with a safety profile generally consistent with clinical experience associated with omega-3 fatty acids and current
Subgroups and other REDUCE-IT information: Positive REDUCE-IT results were consistent across various patient subgroups, including female/male, diabetic/non-diabetic and secondary/primary prevention. At baseline, approximately 59% and 71% of the patients had diabetes and established cardiovascular disease, respectively. Approximately 71% of the patients studied were classified as Westernized with the largest cohort from
Differentiated result and mechanism of action: The success of REDUCE-IT is distinct from past failures to show significant benefit of other agents that lower triglyceride levels when studied on top of statin therapy, including mixtures of omega-3 fatty acids, fenofibrates, niacin and CETP inhibitors. In REDUCE-IT, the median change in triglyceride levels from baseline to year one was -18.3% (-39 mg/dL) for Vascepa and +2.2% (4.5 mg/dL) for placebo; placebo-corrected median change from baseline of -19.7% (-44.5 mg/dL; p=<0.001). As expressed in
The active pharmaceutical ingredient in Vascepa has a unique molecular structure. Vascepa has demonstrated clinical effects that have not been shown for any other product. The clinical effects of Vascepa demonstrated in REDUCE-IT cannot be generalized to any other product.
Mechanisms responsible for Vascepa’s effects in the REDUCE-IT study were not directly evaluated in the outcomes study. Independent of REDUCE-IT,
Scientific presentation: Presentation of the REDUCE-IT results at AHA were made by the Global Principal Investigator and Steering Committee Chair for the study,
Dr. Bhatt stated, “REDUCE-IT establishes a new paradigm for the prevention of important cardiovascular events in statin-treated patients at elevated risk with increased triglycerides. I believe that the results of this study may represent the most significant breakthrough in preventative cardiovascular care since the introduction of statin therapy decades ago.”
“The robustness and consistency of these clinical results are exciting. Extensive scientific evaluation led to the design and conduct of this study; but the degree of benefit shown with Vascepa nevertheless exceeded our expectation,” stated
“Amarin has spent over
The REDUCE-IT study was designed under a special protocol assessment agreement with the
Vascepa is Affordably Priced
Vascepa is a low-cost drug. The majority of patients covered by insurance who obtain prescriptions for Vascepa pay a monthly co-pay charge of
Commercial Expansion and Next Steps
As previously described,
Conference Call and Webcast Information
Amarin will host a conference call at 7:15 p.m. CT/ 8:15 p.m. ET, November 10, 2018 to discuss this information. The call will be accessible through the investor relations section of the company’s website at www.amarincorp.com. The call can also be heard via telephone by dialing 877-407-8033. A replay of the call will be made available for a period of two weeks following the conference call. To hear a replay of the call, dial 877-481-4010 (inside
About Cardiovascular Disease
Worldwide, cardiovascular disease (CVD) remains the #1 killer of men and women. In
Multiple primary and secondary prevention trials have shown a significant reduction of 25% to 35% in the risk of cardiovascular events with statin therapy, leaving significant persistent residual risk despite the achievement of target LDL-C levels.4
Beyond the cardiovascular risk associated with LDL-C, genetic, epidemiologic, clinical and real-world data suggest that patients with elevated triglycerides (TG) (fats in the blood), and TG-rich lipoproteins, are at increased risk for cardiovascular disease. 11, 12, 13, 14
About VASCEPA® (icosapent ethyl) Capsules
Vascepa® (icosapent ethyl) capsules are a single-molecule prescription product consisting of the omega-3 acid commonly known as
Indication and Usage Based on Current FDA-Approved Label (not including REDUCE-IT results)
- Vascepa (icosapent ethyl) is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia.
- The effect of Vascepa on the risk for pancreatitis and cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia has not been determined.
Important Safety Information for Vascepa Based on Current FDA-Approved Label (not including REDUCE-IT results) (Includes Data from Two 12-Week Studies (n=622) (MARINE and ANCHOR) of Patients with Triglycerides Values of 200 to 2000 mg/dL)
- Vascepa is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to Vascepa or any of its components.
- In patients with hepatic impairment, monitor ALT and AST levels periodically during therapy.
- Use with caution in patients with known hypersensitivity to fish and/or shellfish.
- The most common reported adverse reaction (incidence >2% and greater than placebo) was arthralgia (2.3% for Vascepa, 1.0% for placebo). There was no reported adverse reaction >3% and greater than placebo.
- Adverse events and product complaints may be reported by calling 1-855-VASCEPA or the
FDAat 1-800- FDA-1088.
- Patients receiving treatment with Vascepa and other drugs affecting coagulation (e.g., anti-platelet agents) should be monitored periodically.
- Patients should be advised to swallow Vascepa capsules whole; not to break open, crush, dissolve, or chew Vascepa.
FULL VASCEPA PRESCRIBING INFORMATION CAN BE FOUND AT WWW.VASCEPA.COM.
Vascepa has been approved for use by the
Important Cautionary Information About REDUCE-IT Primary Results
Further REDUCE-IT data assessment and data release could yield additional useful information to inform greater understanding of the trial outcome. Further detailed data assessment by
This press release contains forward-looking statements, including expectations regarding planned regulatory filings and the nature of FDA’s review and related timing thereof; expectations that REDUCE-IT results could lead to a new treatment paradigm in the patient population studied; and plans for sales force, international and insurance coverage expansion. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. In addition,
Availability of Other Information About Amarin
Investors and others should note that
1 LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352: 1425–35.
2 Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713.
3 Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. DOI: 10.1056/NEJMoa1812792.
4 Ganda OP, Bhatt DL, Mason RP, et al. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol. 2018;72(3):330-343.
5 Borow KM, Nelson JR, Mason RP. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (
6 Nelson JR, Wani O, May HT, et al. Potential benefits of eicosapentaenoic acid on atherosclerotic plaques. Vascul Pharmacol. 2017;91:1–9.
7 Mason RP, Dawoud H, Jacob RF, et al. Eicosapentaenoic acid improves endothelial function and nitric oxide bioavailability in a manner that is enhanced in combination with a statin. Biomed Pharmacother. 2018;103:1231-1237.
8 Takamura M, Kurokawa K, Ootsuji H, et al. Long-term administration of eicosapentaenoic acid improves post-myocardial infarction cardiac remodeling in mice by regulating macrophage polarization.
11 Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.
12 Toth PP, Granowitz C, Hull M, et al. High triglycerides are associated with increased cardiovascular events, medical costs, and resource use: A real-world administrative claims analysis of statin-treated patients with high residual cardiovascular risk.
13 Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology. Circ Res. 2016;118:547-563.
14 Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384:626–635.
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Source: Amarin Corporation plc