Repatha is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove low-density lipoprotein cholesterol (LDL-C), or “bad” cholesterol, from the blood.1
“We are pleased to announce that we have completed full enrollment in our cardiovascular outcomes trial, FOURIER, which was designed to investigate whether there is a substantial reduction in the occurrence of major cardiovascular events with the use of Repatha,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “We look forward to the results from this important outcomes study for patients with clinically evident cardiovascular disease and high cholesterol.”
FOURIER, a Phase 3 randomized, multicenter, double-blind, placebo-controlled trial, is designed to evaluate whether treatment with Repatha in combination with statin therapy compared to placebo plus statin therapy reduces recurrent cardiovascular events. The primary endpoint in the study is the time to cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke or coronary revascularization. Secondary endpoints include time to cardiovascular death, myocardial infarction or stroke; time to death by any cause; time to cardiovascular death or hospitalization for worsening heart failure; and time to ischemic fatal or non-fatal stroke or transient ischemic attack.
Eligible patients with high cholesterol (LDL-C ≥70 mg/dL or non-high-density lipoprotein cholesterol [non-HDL-C] ≥100 mg/dL) and clinically evident cardiovascular disease at more than 1,200 study locations around the world were randomized to receive subcutaneous Repatha 140 mg every two weeks or 420 mg monthly plus effective statin dose; or subcutaneous placebo every two weeks or monthly plus effective statin dose. Effective statin dose is defined as greater than or equal to atorvastatin 20 mg or an equivalent statin.
“High cholesterol is an important modifiable risk factor for coronary heart disease and stroke,” said Marc S. Sabatine, M.D., M.P.H., co-chairman of the FOURIER executive committee, chairman of TIMI Study Group, senior physician in the Division of Cardiovascular Medicine, Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, Boston. “We are eager to see if evolocumab will reduce the rate of cardiovascular events in patients at high risk for another event when it is added to standard of care.”
The U.S. Food and Drug Administration (FDA) has set a Prescription Drug User Fee Act (PDUFA) target action date of Aug. 27, 2015, for the Repatha Biologics License Application (BLA).
Additional information on the FOURIER trial and other Repatha clinical studies can be found atwww.clinicaltrials.gov.
High cholesterol, particularly elevated LDL-C, is the most common form of dyslipidemia, which is an abnormality of cholesterol and/or fats in the blood.2,3 Elevated LDL-C is recognized as a major risk factor for cardiovascular disease.4,5 There are approximately 300 million cases of dyslipidemia in the U.S., Japan and Western Europe.6
About RepathaTM (evolocumab)
RepathaTM (evolocumab) is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9).1 PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver’s ability to remove LDL-C, or “bad” cholesterol, from the blood.7 Repatha, being developed by Amgen scientists, is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.1
The FDA has provisionally approved the use of the trade name Repatha.
About PROFICIO: RepathaTM (evolocumab) Clinical Trial Program
PROFICIO, which stands for the Program to Reduce LDL-C and Cardiovascular OutcomesFollowing Inhibition of PCSK9 In Different POpulations, is a large and comprehensive clinical trial program evaluating RepathaTM (evolocumab) in 22 clinical trials, with a combined planned enrollment of approximately 35,000 patients.
The Phase 3 program includes 16 trials to evaluate Repatha administered every two weeks and monthly in multiple patient populations, including in combination with statins in patients with hyperlipidemia (LAPLACE-2 and YUKAWA-2); in patients with hyperlipidemia who cannot tolerate statins (GAUSS-2 and GAUSS-3); as a stand-alone treatment in patients with hyperlipidemia (MENDEL-2); in patients whose elevated cholesterol is caused by genetic disorders called heterozygous (RUTHERFORD-2 and TAUSSIG) and homozygous (TESLA and TAUSSIG) familial hypercholesterolemia; the effects of Repatha on lipoprotein metabolism (FLOREY); and the administration of Repatha in statin-treated hyperlipidemic patients (THOMAS-1 and THOMAS-2).
Five ongoing studies in the Repatha Phase 3 program will provide long-term safety and efficacy data. These include FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), which will assess whether treatment with Repatha in combination with statin therapy compared to placebo plus statin therapy reduces recurrent cardiovascular events in approximately 27,500 patients with cardiovascular disease; EBBINGHAUS (Evaluating PCSK9 Binding AntiBody Influence oN CoGnitive HeAlth in High CardiovascUlar Risk Subjects), which will evaluate the effect of Repatha on cognitive function in a subset of patients enrolled in FOURIER; OSLER-2 (Open Label Study of Long TERm Evaluation Against LDL-C Trial-2) in patients with high cholesterol who completed any of the Phase 3 studies; GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound), which will determine the effect of Repatha on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization; and TAUSSIG (Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects with Genetic LDL Disorders), which will assess the long-term safety and efficacy of Repatha on LDL-C in patients with severe familial hypercholesterolemia including patients with homozygous familial hypercholesterolemia. The DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) study, a long-term safety and efficacy trial in patients with hyperlipidemia at risk for cardiovascular disease, has completed.
About Amgen’s Commitment to Cardiovascular Disease
Building on more than three decades of experience in developing biotechnology medicines for patients with serious illnesses, Amgen is dedicated to addressing important scientific questions to advance care and improve the lives of patients with cardiovascular disease, the leading cause of morbidity and mortality worldwide.8 Amgen’s research into cardiovascular disease, and potential treatment options, is part of a growing competency at Amgen that utilizes human genetics to identify and validate certain drug targets. Through its own research and development efforts, as well as partnerships, Amgen is building a robust cardiovascular pipeline consisting of several investigational molecules in an effort to address a number of today’s important unmet patient needs, such as high cholesterol and heart failure.
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
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CONTACT: Amgen, Thousand Oaks
Kristen Davis, 805-447-3008 (media)
Trish Hawkins, 805-447-5631 (media)
Arvind Sood, 805-447-1060 (investors)
- Amgen Data on File, Investigator Brochure.
- World Health Organization. Quantifying Selected Major Risks to Health. In: The World Health Report 2002 – Reducing Risks, Promoting Healthy Life. Geneva. 2002:49-97.
- Merck Manuals website.http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/lipid_disorders/dyslipidemia.html. Accessed May 2015.
- American Heart Association (2012). Why cholesterol matters.http://www.heart.org/HEARTORG/Conditions/Cholesterol/WhyCholesterolMatters/Why-Cholesterol-Matters_UCM_001212_Article.jsp. Accessed May 2015.
- World Health Organization. Global status report on noncommunicable diseases 2014. Geneva, 2014.
- National Institute of Health (2009). Federal Register Volume 74 (250). Washington, DC: U.S. Government Printing Office. http://www.gpo.gov/fdsys/pkg/FR-2009-12-31/html/E9-31072.htm. Accessed May 2015.
- Qian Y-W, Schmidt RJ, Zhang Y, et al. Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J. Lipid Res. 2007;48:1488-1498.
- World Health Organization. Cardiovascular diseases (CVDs) fact sheet.http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed May 2015.
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