SOURCE: Amarin Corp. Plc

Amarin

November 09, 2015 08:07 ET

EPA Therapy Added to Statin Therapy Showed Coronary Plaque Regression at Approximately Twice the Prevalence Compared to Statin Therapy Alone in Japanese Clinical Study

BEDMINSTER, NJ AND DUBLIN, IRELAND--(Marketwired - November 09, 2015) - Amarin Corporation plc (NASDAQ: AMRN) today commented on new data from the CHERRY study that supports the hypothesis under investigation in Amarin's cardiovascular outcomes study of Vascepa® (icosapent ethyl) capsules, the REDUCE-IT trial: that highly purified EPA drug therapy may reduce residual risk in coronary heart disease (CHD) patients already on lipid-lowering statin therapy.

The CHERRY study was a randomized, non-blinded, parallel group, multicenter study designed to investigate whether coronary plaque regression and stabilization are reinforced by additional administration of EPA to pitavastatin (PTV 4 mg/day) therapy in patients. Approximately 200 adult Japanese CHD patients who underwent percutaneous coronary intervention were randomly allocated to either the statin only group (n=96) or to the statin/EPA (1.8 g/day) group (n=97), prospectively followed for 6 to 8 months, and included in the primary analysis. Coronary plaque volume and composition in non-stenting lesions were analyzed by integrated backscatter-intravascular ultrasonography (IB-IVUS) at baseline and follow up. The primary endpoint was the change in coronary tissue characteristics as evaluated by IB-IVUS. Secondary end points included changes in the volume of target coronary plaques and major cardiovascular events. Baseline low-density lipoprotein cholesterol levels for the statin and statin/EPA groups were 99 and 107 mg/dL, respectively, and total cholesterol levels were 166 and 175 mg/dL, respectively. Triglyceride levels were in the normal range at baseline in both arms [1].

After 6-8 months the CHERRY study showed a statistically significant reduction in coronary plaque volume (from 74.5 to 61.4 mm3; p<0.001), lipid volume (from 39.2 to 34.8 mm3; p<0.05), and fibrous volume (from 28.9 to 22.8 mm3; p<0.05) of the lesions in the statin plus EPA group, but in each case no statistically significant difference was observed in the statin-only group. The prevalence of clinically significant plaque regression, defined as percent change in plaque volume more than -15%, was significantly greater in the statin plus EPA group than in the statin group alone (48% vs. 25%; p<0.001).

Patient safety was evaluated by regular medical examinations and laboratory tests at 1, 3, and 6-8 months after enrollment. An assessment committee evaluated major adverse cardiovascular events (MACE) and any other adverse events. In this short-term study of <100 patients per arm, there were no statistically significant differences between groups in MACE or adverse events. MACE was defined as cardiac death, myocardial infarction, PCI and coronary artery bypass graft.

CHERRY is the first known study to use IB-IVUS to investigate the effects of combination therapy with statin and EPA on plaque regression. Coronary atherosclerosis progression/regression evaluation by IVUS is reported to be a feasible means to predict future cardiovascular events [2,3], and IB-IVUS analysis of specific tissue components (calcification, dense fibrosis, fibrosis, lipid pool) of coronary plaques in vivo [4,5] has been considered a useful tool for assessing risk of experiencing a coronary event in patients with coronary atherosclerosis [6-8].

The CHERRY study was not sponsored by or affiliated with Amarin. The study was presented by Dr. Kaoru Ando (Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan) and his colleagues at the American Heart Association Scientific Sessions in Orlando, Florida on November 8 and the abstract has been published in Circulation. 2015; 132: A12007. Information in this press release is based on publicly presented data. Amarin disclaims responsibility for inaccuracies of third-party publicly presented data. Amarin looks forward to publication of complete results from the CHERRY study to more fully assess the strengths and limitations of the study and the resulting data.

The CHERRY investigators concluded from their study that additional administration of EPA to high dose statin treatment significantly reduced coronary plaque volume and suggested from their study results that EPA therapy may reduce the residual risk that remains in secondary prevention patients being treated with statin therapy [9-10].

About the REDUCE-IT study

REDUCE-IT (Reduction of Cardiovascular Events with EPA - Intervention Trial), is a multinational, prospective, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the effectiveness of 4 grams daily of Vascepa, the active ingredient in which is EPA, in reducing the prevalence of first major cardiovascular events in a high-risk patient population. The control arm of the study is comprised of patients on stable statin therapy plus placebo. The active arm of the study is comprised of patients on stable statin therapy plus Vascepa.

Patients enrolled in the REDUCE-IT study have elevated or high triglyceride levels despite statin therapy and either coronary heart disease or risk factors for coronary heart disease.

The REDUCE-IT study is designed with a composite MACE (Major Adverse Cardiovascular Event) endpoint of cardiovascular death, nonfatal myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina caused by myocardial ischemia. The study also includes secondary and tertiary endpoints and subgroup analyses agreed-upon with FDA.

The REDUCE-IT trial continues on schedule towards anticipated completion in 2017 and publication of results in 2018. Completion of the REDUCE-IT study is based on attainment of 1,612 cumulative patients with documented primary cardiovascular events. The results of this important trial could lead to improved medical care for tens of millions of patients.

Amarin is blinded to the ongoing study results. An interim review by the independent data monitoring committee (DMC) of the trial's efficacy and safety results is expected to occur during 2016 upon reaching 60% of the target aggregate number of cardiovascular events. Based on comprehensive review of clinical, epidemiological, and genetic data, Amarin continues to believe that REDUCE-IT is positioned for success at completion. Given the high thresholds of overwhelming efficacy and safety typically required to be achieved prior to an independent DMC recommending an early stop to a cardiovascular outcomes trial like REDUCE-IT, Amarin continues to believe that it is most likely that the REDUCE-IT study will run to its completion.

More than 7,700 patients have been enrolled in the REDUCE-IT cardiovascular outcomes study representing more than 97% of total targeted patient enrollment in this event-driven study.

About Amarin

Amarin Corporation plc is a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health. Amarin's product development program leverages its extensive experience in lipid science and the potential therapeutic benefits of polyunsaturated fatty acids. Amarin's clinical program includes commitment to an ongoing outcomes study. Amarin's first product, Vascepa® (icosapent ethyl) capsules, is a highly pure EPA omega-3 prescription product. For more information about Vascepa visit www.vascepa.com. For more information about Amarin visit www.amarincorp.com.

About VASCEPA® (icosapent ethyl) capsules

VASCEPA® (icosapent ethyl) capsules, known in scientific literature as AMR101, is a highly pure-EPA omega-3 prescription product in a 1 gram capsule.

Indications and Usage

  • 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

  • VASCEPA is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to VASCEPA or any of its components.
  • 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.
  • Patients receiving treatment with VASCEPA and other drugs affecting coagulation (e.g., anti-platelet agents) should be monitored periodically.
  • In patients with hepatic impairment, monitor ALT and AST levels periodically during therapy.
  • Patients should be advised to swallow VASCEPA capsules whole; not to break open, crush, dissolve, or chew VASCEPA.
  • Adverse events and product complaints may be reported by calling 1-855-VASCEPA or the FDA at 1-800-FDA-1088.

FULL VASCEPA PRESCRIBING INFORMATION CAN BE FOUND AT WWW.VASCEPA.COM.

Vascepa has been approved for use by the FDA as an adjunct to diet to reduce triglyceride levels in adult patients with severe (>500 mg/dL) hypertriglyceridemia. Vascepa is under various stages of development for potential use in other indications that have not been approved by the FDA. Nothing in this press release should be construed as promoting the use of Vascepa in any indication that has not been approved by the FDA.

Further study such as the REDUCE-IT trial is needed to determine if the effects of Vascepa can reduce residual risk in coronary heart disease patients already on statin therapy.

Forward-looking statements

This press release contains forward-looking statements, including statements about the potential efficacy, safety and therapeutic benefits of EPA and Amarin's product candidates, Amarin's statements regarding clinical trial results, including statements about the clinical importance of certain biomarkers and the impact and potential impact of EPA drug therapy and Vascepa on such biomarkers, cardiovascular risk reduction after statin therapy and the endpoints defined in the REDUCE-IT study. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, including the risk that historical and comparable clinical trial results may not be predictive of future REDUCE-IT study results, that regulatory reviews may impact the current design of the REDUCE-IT study and cause a change in strategic direction with respect to continuation of the study, and that changes in studied lipid biomarkers may not have clinically meaningful effect or support regulatory approvals. A further list and description of these risks, uncertainties and other risks associated with an investment in Amarin can be found in Amarin's filings with the U.S. Securities and Exchange Commission, including its most recent Quarterly Report on Form 10-Q. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Amarin undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

REFERENCES

  1. Ando K, Wantanabe T, Daidoji H, et al. Combination Therapy of Eicosapentaenoic Acid and Pitavastatin for Coronary Plaque Regression Evaluated by Integrated Backscatter Intravascular Ultrasonography: A Randomized Controlled Trial. Circulation. 2015;132:A12007.
  2. Dohi T, Miyauchi K, Okazaki S, Yokoyama T, Yanagisawa N, Tamura H, Kojima T, Yokoyama K, Kurata T, Daida H. Plaque regression determined by intravascular ultrasound predicts long-term outcomes of patients with acute coronary syndrome. J Atheroscler Thromb. 2011;18:231-9.
  3. Miyauchi K, Daida H, Morimoto T, Hiro T, Kimura T, Nakagawa Y, Yamagishi M,Ozaki Y, Kadota K, Kimura K, Hirayama A, Hasegawa Y, Uchiyama S, Matsuzaki M. Reverse vessel remodeling but not coronary plaque regression could predict future cardiovascular events in ACS patients with intensive statin therapy-the extended JAPAN-ACS study. Circ J. 2012;76:825-32.
  4. Amano T, Matsubara T, Uetani T, Nanki M, Marui N, Kato M, Arai K, Yokoi K,Ando H, Ishii H, Izawa H, Murohara T. Impact of metabolic syndrome on tissue characteristics of angiographically mild to moderate coronary lesions integrated backscatter intravascular ultrasound study. J Am Coll Cardiol. 2007;49:1149-56.
  5. Kawasaki M, Takatsu H, Noda T, Sano K, Ito Y, Hayakawa K, Tsuchiya K, AraiM, Nishigaki K, Takemura G, Minatoguchi S, Fujiwara T, Fujiwara H. In vivo quantitative tissue characterization of human coronary arterial plaques by use of integrated backscatter intravascular ultrasound and comparison with angioscopic findings. Circulation. 2002;105:2487-92.
  6. Okubo M, Kawasaki M, Ishihara Y, Takeyama U, Yasuda S, Kubota T, TanakaYamaki T, Ojio S, Nishigaki K, Takemura G, Saio M, Takami T, Fujiwara H,Minatoguchi S. Tissue characterization of coronary plaques: comparison of integrated backscatter intravascular ultrasound with virtual histology intravascular ultrasound. Circ J. 2008;72:1631-9.
  7. Amano T, Matsubara T, Uetani T, Kato M, Kato B, Yoshida T, Harada K, Kumagai S, Kunimura A, Shinbo Y, Ishii H, Murohara T. Lipid-rich plaques predict nontarget-lesion ischemic events in patients undergoing percutaneous coronary intervention. Circ J. 2011;75:157-66.
  8. Sano K, Kawasaki M, Ishihara Y, Okubo M, Tsuchiya K, Nishigaki K, Zhou X, Minatoguchi S, Fujita H, Fujiwara H. Assessment of vulnerable plaques causing acute coronary syndrome using integrated backscatter intravascular ultrasound. J Am Coll Cardiol. 2006;47:734-41.
  9. Bayturan O, Kapadia S, Nicholls SJ, et al. Clinical predictors of plaque progression despite very low levels of low-density lipoprotein cholesterol. J Am Coll Cardiol. 2010;55:2736-2742.
  10. Matsuzaki M, Yokoyama M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, et al. Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease. Circ J. 2009;73:1283-90.

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