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Critical Milestone for Patients With Uncontrolled Cholesterol who Require Additional Intensive LDL-C Reduction
THOUSAND OAKS, Calif. (July 21, 2015) – Amgen (NASDAQ:AMGN) today announced that the European Commission (EC) has granted marketing authorization for RepathaTM (evolocumab), the first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to be approved in the world, for the treatment of patients with uncontrolled cholesterol who require additional intensive low-density lipoprotein cholesterol (LDL-C) reduction. Repatha is a human monoclonal antibody that inhibits PCSK9, a protein that reduces the liver's ability to remove LDL-C, or “bad” cholesterol, from the blood.1 Elevated LDL-C is an abnormality of cholesterol and/or fats in the blood,2,3 and is recognized as a major risk factor for cardiovascular disease (CVD).4,5
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The EC approved Repatha for:
The effect of Repatha on cardiovascular morbidity and mortality has not yet been determined.
More than 60 percent of high-risk patients in Europe are still unable to adequately lower their LDL-C levels with statins or other currently approved lipid-lowering agents. Among very high-risk patients, the percentage is increased to more than 80 percent.6 The health care cost of CVD in the European Union (EU) is approximately €106 billion per year.7
“We are proud that our cholesterol-lowering medication, Repatha, is the first PCSK9 inhibitor to be approved by any regulatory agency in the world,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “High LDL cholesterol is a major global health burden and many patients are unable to appropriately control their LDL cholesterol with the maximum tolerated dose of a statin, or are unable to take statins due to intolerance or contraindications. We are excited to make this new cholesterol-lowering medication available for patients in Europe.”
One high-risk patient group includes those with familial hypercholesterolemia (FH), an inherited condition caused by genetic mutations which lead to high levels of LDL-C at an early age.8 It is estimated that less than one percent of people with FH (heterozygous and homozygous forms) in most countries are diagnosed.9
“Many patients who are taking cholesterol-lowering therapies, including those with familial hypercholesterolemia, still struggle to control their LDL cholesterol levels,” said John J.P. Kastelein, professor of medicine and chairman of the Department of Vascular Medicine at the Academic Medical Center (AMC) of the University of Amsterdam. “As the first in a new class of drugs in the European Union, evolocumab will offer physicians an important and innovative treatment option for patients with uncontrolled cholesterol who require additional LDL cholesterol reduction.”
Approval from the EC grants a centralized marketing authorization with unified labeling 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.
Data show Repatha has demonstrated substantial and consistent reductions in LDL-C levels with supporting beneficial changes in other lipid parameters in approximately 6,000 patients with primary hyperlipidemia and mixed dyslipidemia, including more than 4,500 patients with high cholesterol in 10 Phase 3 trials.10 In these studies, Repatha significantly reduced LDL-C by approximately 55 percent to 75 percent compared with placebo,11-14 and by approximately 35 percent to 45 percent compared with ezetimibe.11,12,14 In patients with homozygous FH, Repatha significantly reduced LDL-C by approximately 15 percent to 30 percent compared with placebo.15 Reduction of LDL-C was maintained with long-term treatment.16
The adverse event profile for Repatha was comparable overall to that of the control groups.11-17 The most common adverse reactions that occurred in greater than or equal to 2 percent of the Repatha group, and more frequently than in the control group, were nasopharyngitis, upper respiratory tract infection, back pain, arthralgia, influenza and nausea. Please consult the Summary of Product Characteristics (SmPC) for full safety information.
Repatha is for subcutaneous injection into the abdomen, thigh or upper arm region. Injection sites should be rotated and injections should not be given into areas where the skin is tender, bruised, red or hard. Repatha must not be administered intravenously or intramuscularly. Before starting treatment with Repatha, secondary causes (non-genetic) of excess cholesterol and abnormal fat levels in blood should be excluded. The medicine can only be obtained with a prescription.
The recommended dose for adults with primary disease is either 140 mg every two weeks or 420 mg (the contents of three pre-filled syringes) once a month; both doses are clinically equivalent. For adults or children older than 12 years with homozygous FH, the initial recommended dose is 420 mg once a month. If a response is not achieved after 12 weeks of treatment, the dose can be increased up to 420 mg every two weeks. For more information, see the package leaflet.
About RepathaTM (evolocumab)
RepathaTM (evolocumab) is a 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.18 Repatha, 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
Important EU Product Information
Hypercholesterolemia and mixed dyslipidemia
Repatha is indicated in adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, as an adjunct to diet:
Homozygous familial hypercholesterolemia
Repatha is indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolemia in combination with other lipid-lowering therapies.
Important Safety Information
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Contraindications: Hypersensitivity to the active substance or to any of the excipients.
Special Warnings and Precautions: Renal impairment: Patients with severe renal impairment (defined as eGFR < 30 mL/min/1.73 m2) have not been studied. Repatha should be used with caution in patients with severe renal impairment. Hepatic impairment: In patients with moderate hepatic impairment, a reduction in total evolocumab exposure was observed that may lead to a reduced effect on LDL‑C reduction. Therefore, close monitoring may be warranted in these patients. Patients with severe hepatic impairment (Child-Pugh C) have not been studied. Repatha should be used with caution in patients with severe hepatic impairment. Dry natural rubber: The needle cover of the glass pre-filled syringe and of the pre-filled pen is made from dry natural rubber (a derivative of latex), which may cause allergic reactions. Sodium content: Repatha contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially ‘sodium-free’.
Interactions: No formal drug-drug interaction studies have been conducted for Repatha. No studies on pharmacokinetic and pharmacodynamics interaction between Repatha and lipid-lowering drugs other than statins and ezetimibe have been conducted.
Fertility, Pregnancy and Lactation: There are no or limited amount of data from the use of Repatha in pregnant women. Repatha should not be used during pregnancy unless the clinical condition of the woman requires treatment with evolocumab. It is unknown whether evolocumab is excreted in human milk. A risk to breastfed newborns/infants cannot be excluded. No data on the effect of evolocumab on human fertility are available.
Undesirable Effects: The following common (≥ 1/100 to < 1/10) adverse reactions have been reported in pivotal, controlled clinical studies: influenza, nasopharyngitis, upper respiratory tract infection, rash, nausea, back pain, arthralgia, injection site reactions. Please consult the SmPC for a full description of undesirable effects.
Pharmaceutical Precautions: Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the pre-filled syringe or the pre-filled pen in the original carton in order to protect from light. If removed from the refrigerator, Repatha may be stored at room temperature (up to 25°C) in the original carton and must be used within 1 week.
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.19 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 cardiovascular portfolio consisting of several approved and 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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10. Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events. N Engl J Med. 2015;372:1500-1509.
11. Koren MJ, Lundqvist P, Bolognese M, et al. Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol. 2014;63:2531-2540.
12. Robinson JG, Nedergaard BS, Rogers WJ, et al. Effect of evolocumab or ezetimibe added to moderate or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia. The LAPLACE-2 randomized clinical trial. JAMA. 2014;311:1870-1882.
13. Raal FJ, Stein EA, Dufour R, et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385:331-340.
14. Stroes E, Colquhoun D, Sullivan D, et al. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014;63:2541-2548.
15. Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385:341-50.
16. Blom DJ, Hala T, Bolognese M. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014;370:1809-1819.
17. Koren MJ, Giugliano RP, Raal FJ, et al. Efficacy and Safety of Longer-Term Administration of Evolocumab (AMG 145) in Patients With Hypercholesterolemia: 52-Week Results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) Randomized Trial. Circulation. 2014;129:234-243.
18. Lopez D. PCSK9: An enigmatic protease. Biochimica et Biophysica Acta. 2008;1781:184-191.
19. World Health Organization. Cardiovascular diseases (CVDs) fact sheet. http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed July 2015.