First Positive Regulatory Agency Determination for a PCSK9 Inhibitor
THOUSAND OAKS, Calif., May 22, 2015 /PRNewswire/ -- Amgen (AMGN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for the marketing authorization of Repatha™ (evolocumab) recommending approval for use in certain patients with high cholesterol. 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
The CHMP recommended granting Repatha marketing authorization for:
The treatment of adults with primary hypercholesterolemia (heterozygous familial and non-familial [HeFH]) or mixed dyslipidemia, as an adjunct to diet:
in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin, or
alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.
The treatment of adults and adolescents aged 12 years and over with homozygous familial hypercholesterolemia (HoFH) in combination with other lipid-lowering therapies.
The effect of Repatha on cardiovascular morbidity and mortality has not yet been determined.
"We are pleased to receive a positive opinion from the CHMP for Repatha as it is an important step in providing a new treatment option for patients with high cholesterol, who are unable to reach their LDL cholesterol goals with current therapies in the European Union," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Uncontrolled high cholesterol is a burden on the health system and we look forward to continuing to work with regulatory authorities to bring Repatha to patients across Europe."
The Icelandic and Norwegian CHMP members have also agreed with the above-mentioned recommendation on granting of the marketing authorization.
The CHMP positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). If approved, a centralized marketing authorization with unified labeling will be granted in the 28 countries that are members of the EU. Norway, Iceland and Liechtenstein, as members of the European Economic Area (EEA), will take corresponding decisions on the basis of the decision of the EC.
The CHMP opinion is based on data from approximately 6,800 patients, including more than 4,500 patients with high cholesterol in 10 Phase 3 trials. The Phase 3 studies evaluated the safety and efficacy of Repatha in patients with elevated cholesterol, including patients on statins with or without other lipid-lowering therapies; patients who cannot tolerate statins; patients with HeFH; and patients with HoFH, a rare and serious genetic disorder.2
In Europe, up to 54 percent of the population aged 25 and older has a total cholesterol ≥5.0 mmol/L (≥190 mg/dL).3 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.4,5 Elevated LDL-C is recognized as a major risk factor for cardiovascular disease.6,7
About Repatha™ (evolocumab)
Repatha™ (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.8 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 U.S. Food and Drug Administration (FDA) and EMA have provisionally approved the use of the trade name Repatha.
About PROFICIO: Repatha™ (evolocumab) Clinical Trial Program
PROFICIO, which stands for the Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations, is a large and comprehensive clinical trial program evaluating Repatha™ (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 Cardiovascular
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.9 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.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
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CONTACT: Amgen, Thousand Oaks
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Arvind Sood, 805-447-1060 (investors)
Amgen, European Union
Emma Gilbert, +41 41 369 2542
Amgen Data on File, Investigator Brochure.
National Human Genome Research Institute. Learning About Familial Hypercholesterolemia. http://www.genome.gov/25520184. Accessed May 2015.
World Health Organization: Global Health Observatory (GHO) data; Raised Cholesterol situations and trends; WHO 2015. http://www.who.int/gho/ncd/risk_factors/cholesterol_text/en/
World Health Organization. Quantifying Selected Major Risks to Health. In: The World Health Report 2002 - Reducing Risks, Promoting Healthy Life. Chapter 4: Geneva: World.
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 2010. Geneva, 2011.
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.