New detailed data from three phase 3 pivotal studies show Amgen's novel investigational cholesterol-lowering medicine evolocumab significantly reduced LDL Cholesterol by 55-66 per cent compared to placebo in patients with high cholesterol Data From Three Separate Phase 3 Studies of Evolocumab (AMG 145), a PCSK9 Inhibitor, Presented as Featured Clinical Research at ACC.14 Data From Two Additional Phase 3 Studies on Evolocumab Presented in Late-Breaking Session at ACC.14 Please Note: This information is intended for Canadian media only. The safety and efficacy of evolocumab are still under investigation, and Amgen has not yet obtained authorization from Health Canada for sale of the product in Canada. MISSISSAUGA, ON, March 31, 2014 /CNW/ - Amgen Canada Inc. today announced new detailed data from three Phase 3 studies that showed treatment with its novel investigational cholesterol-lowering medication, evolocumab (AMG 145), resulted in a statistically significant reduction of 55-66 per cent in low-density lipoprotein cholesterol (LDL-C) compared to placebo in patients with high cholesterol. Results from the three separate Phase 3 studies, MENDEL-2, DESCARTES and RUTHERFORD-2, were presented as Featured Clinical Research in a Special Session at the American College of Cardiology's 63(rd) Annual Scientific Session (ACC.14). Data from DESCARTES, the long-term safety and efficacy study, were simultaneously published in the New England Journal of Medicine and data from MENDEL-2, the monotherapy study, were simultaneously published in the Journal of the American College of Cardiology. Evolocumab 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 LDL-C from the blood.(1) The three Phase 3 studies evaluated evolocumab in different patient populations: as monotherapy in patients with high cholesterol (MENDEL-2); as a long-term 52-week therapy in patients with high cholesterol on risk-based lipid-lowering therapy (DESCARTES); and in combination with statins and other lipid-lowering therapies in patients with heterozygous familial hypercholesterolemia (HeFH), a genetic disorder characterized by elevated LDL-C levels (RUTHERFORD-2). In MENDEL-2, the most common adverse events (AEs) (≥ 2 per cent in evolocumab combined group) were headache, diarrhea, nausea and urinary tract infection. The most common AEs (> 5 per cent in evolocumab) in the DESCARTES study were nasopharyngitis, upper respiratory tract infection, influenza and back pain. In RUTHERFORD-2, the most common (≥ 2 per cent in the combined evolocumab group) were nasopharyngitis, headache, contusion (i.e., bruise), back pain, nausea, arthralgia, upper respiratory tract infection, influenza, myalgia and pain in extremity. "We are pleased to report positive detailed findings from three of our pivotal studies in key patient populations at risk for cardiovascular disease," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "These results add to the growing body of evidence from our comprehensive Phase 3 clinical trial program. We look forward to working with regulatory authorities on our global filing plan in the hopes of bringing this new treatment option to patients with high cholesterol who have an unmet medical need." MENDEL-2, DESCARTES and RUTHERFORD-2 are three of five Phase 3 evolocumab studies that were presented at ACC.14. Data from two other trials, LAPLACE-2 and GAUSS-2, were featured in a Late-Breaking Clinical Trials session. "Data results from these first Phase 3 studies of evolocumab is relevant for patients with high cholesterol," said Dr. Jacques Genest, Professor, Faculty of Medicine at McGill University. "The results suggest that evolocumab may be a treatment option for those patients who have an unmet medical need and are struggling to keep their LDL-C levels under control." MENDEL-2 (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy For Easing Lipid Levels-2) Primary Results -- The MENDEL-2 study showed that in 614 patients with high cholesterol (LDL-C ≥ 2.6 mmol/L and < 4.9 mmol/L) who were not receiving lipid-lowering therapy, treatment with subcutaneous evolocumab significantly reduced mean LDL-C by 55-57 per cent from baseline compared to placebo and 38-40 per cent from baseline compared to ezetimibe (p<0.001). o Results of the study showed the mean per cent reduction from baseline in LDL-C at weeks 10 and 12 were 57 per cent for evolocumab 140 mg every two weeks and 57 per cent for evolocumab 420 mg monthly compared to placebo; and 39 per cent for evolocumab 140 mg every two weeks and 40 per cent for evolocumab 420 mg monthly compared to ezetimibe. o At week 12, the per cent reduction from baseline in LDL-C was 57 per cent for evolocumab 140 mg every two weeks and 55 per cent for evolocumab 420 mg monthly compared to placebo; and 39 per cent for evolocumab 140 mg every two weeks and 38 per cent for evolocumab 420 mg monthly compared to ezetimibe. -- The most common AEs (≥ 2 per cent in evolocumab combined group) were headache (3.3 per cent evolocumab; 3.2 per cent ezetimibe; 2.6 per cent placebo), diarrhea (2.9 per cent evolocumab; 1.9 per cent ezetimibe; 3.9 per cent placebo), nausea (2.6 per cent evolocumab; 1.9 per cent ezetimibe; 0.6 per cent placebo) and urinary tract infection (2.3 per cent evolocumab; 1.9 per cent ezetimibe; 1.3 per cent placebo). DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) Primary Results -- The DESCARTES study showed that in 901 patients with high LDL-C and a range of cardiovascular risk, evolocumab 420 mg subcutaneous monthly reduced mean LDL-C by 57 per cent from baseline at week 52 compared to placebo (p<0.001). o LDL-C reduction for evolocumab at week 12 was consistent with the long-term efficacy at week 52. o Compared to placebo, the mean per cent LDL-C reductions from baseline with evolocumab at week 52 are 56 per cent, 62 per cent, 57 per cent and 49 per cent in diet alone, atorvastatin 10 mg, atorvastatin 80 mg, and atorvastatin 80 mg plus ezetimibe 10 mg groups, respectively. -- The most common AEs (> 5 per cent in evolocumab) were nasopharyngitis (10.5 per cent evolocumab; 9.6 per cent placebo), upper respiratory tract infection (9.3 per cent evolocumab; 6.3 per cent placebo), influenza (7.5 per cent evolocumab; 6.3 per cent placebo) and back pain (6.2 per cent evolocumab; 5.6 per cent placebo). RUTHERFORD-2 (RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study-2) Primary Results -- The RUTHERFORD-2 study showed that in 329 HeFH patients on a stable dose of statin and other lipid-lowering therapies, treatment with subcutaneous evolocumab significantly reduced mean LDL-C by 59-66 per cent from baseline compared to placebo (p<0.001). o Data show the mean per cent reduction from baseline in LDL-C at weeks 10 and 12 were 60 per cent for evolocumab 140 mg every two weeks and 66 per cent for evolocumab 420 mg monthly compared to placebo. o At week 12, the per cent reduction from baseline in LDL-C was 59 per cent for evolocumab 140 mg every two weeks and 61 per cent for evolocumab 420 mg monthly compared to placebo. -- The most common AEs (≥2 per cent in the combined evolocumab group) were nasopharyngitis (8.6 per cent evolocumab; 4.6 per cent placebo), headache (4.1 per cent evolocumab; 3.7 per cent placebo), contusion (i.e., bruise) (4.1 per cent evolocumab; 0.9 per cent placebo), back pain (3.6 per cent evolocumab; 0.9 per cent placebo), nausea (3.6 per cent evolocumab; 0.9 per cent placebo), arthralgia (3.6 per cent evolocumab; 1.8 per cent placebo), upper respiratory tract infection (3.2 per cent evolocumab; 2.8 per cent placebo), influenza (3.2 per cent evolocumab; 0 per cent placebo), myalgia (2.7 per cent evolocumab; 0 per cent placebo) and pain in extremity (2.3 per cent evolocumab; 2.8 per cent placebo). High cholesterol is the most common form of dyslipidemia, which is an abnormality of lipids in the blood.(2,3) According to the Canadian Health Measures Survey, more than 40 per cent of Canadians aged 20 to 79 have an unhealthy level of total cholesterol.(4 )High blood cholesterol is a major risk factor for heart disease and stroke.(5) Patients with familial hypercholesterolemia, an inherited condition that causes high levels of LDL-C beginning at birth, are at high-risk for cardiovascular events at an early age.(6) Heterozygous familial hypercholesterolemia is one of the most common genetic disorders, affecting approximately one out of every 200 to 500 people worldwide.(7,8) Amgen's webcast investor meeting at ACC.14, as with other selected presentations regarding developments in Amgen's business given by management at certain investor and medical conferences, can be found on Amgen's website, www.amgen.com, under Investors. The webcast will be archived and available for replay for at least 90 days after the event. MENDEL-2 Study Design MENDEL-2 (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy For Easing Lipid Levels-2) is a Phase 3 randomized, multicenter, double-blind, double-dummy, placebo- and ezetimibe-controlled parallel group study designed to evaluate the efficacy and safety of evolocumab in 614 hyperlipidemic patients with a 10-year Framingham risk score of 10 per cent or less who were not receiving lipid-lowering therapy. Patients were randomized to one of six treatment groups to compare two dosing regimens of evolocumab (140 mg every two weeks or 420 mg monthly) with placebo and ezetimibe (10 mg daily). The co-primary endpoints were the per cent reduction from baseline in LDL-C at week 12 and the mean per cent reduction from baseline in LDL-C at weeks 10 and 12. Co-secondary efficacy endpoints included means at weeks 10 and 12 and at week 12 for the following: absolute change from baseline in LDL-C; LDL-C < 1.8 mmol/L; and the percentage change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC)/HDL-C ratio, ApoB/apolipoprotein A1 (ApoA1) ratio, lipoprotein(a), triglycerides, HDL-C and very low-density lipoprotein cholesterol (VLDL-C). DESCARTES Study Design DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) is a Phase 3 randomized, multicenter, double-blind, placebo-controlled study designed to evaluate the long-term (52-week) safety, tolerability and efficacy of evolocumab in patients with hyperlipidemia at risk for cardiovascular disease. Background lipid-lowering therapy was optimized to one of four treatment groups (diet alone; diet plus atorvastatin 10 mg; diet plus atorvastatin 80 mg; and diet plus atorvastatin 80 mg plus ezetimibe 10 mg) for individual patients based on their LDL-C and cardiovascular risk according to the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III risk categories. After optimization, patients were maintained on therapy for at least four weeks. A total of 901 patients with a fasting LDL-C ≥ 1.9 mmol/L were then randomized and received monthly subcutaneous evolocumab 420 mg or placebo in combination with background lipid-lowering therapy. The primary endpoint was per cent change from baseline in LDL-C, measured by the accepted standard, preparative ultracentrifugation, after 52 weeks of treatment. Secondary efficacy endpoints included the absolute change from baseline in LDL-C and LDL-C response (LDL-C <70 mg/dL [1.8 mmol/L]) at week 52, per cent change from baseline in LDL-C and total cholesterol (TC) at week 12, and per cent change from baseline at week 52 in TC, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), TC/HDL-C ratio, ApoB/apolipoprotein A1 (ApoA1) ratio, lipoprotein(a), triglycerides, HDL-C and very low density lipoprotein cholesterol (VLDL-C). RUTHERFORD-2 Study Design RUTHERFORD-2 (RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study-2) is a Phase 3 randomized, multicenter, double-blind, placebo-controlled trial designed to evaluate the safety, tolerability and efficacy of evolocumab in 329 patients with HeFH and an LDL-C ≥ 2.6 mmol/L who were on a stable dose of statin therapy and lipid-lowering medication. Patients were randomized to one of four treatment groups to compare subcutaneous evolocumab (140 mg every two weeks or 420 mg monthly) with subcutaneous placebo (every two weeks or monthly). The co-primary endpoints were the per cent reduction from baseline in LDL-C at week 12 and the mean per cent reduction from baseline in LDL-C at weeks 10 and 12. Co-secondary efficacy endpoints included means at weeks 10 and 12 and at week 12 for the following: absolute change from baseline in LDL-C; LDL-C < 1.8 mmol/L; and the percentage change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC)/HDL-C ratio, ApoB/apolipoprotein A1 (ApoA1) ratio, lipoprotein(a), triglycerides, HDL-C and very low-density lipoprotein cholesterol (VLDL-C). About Evolocumab 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.(9) Evolocumab, 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) About PROFICIO: The 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 evolocumab in 20 clinical trials, with a combined planned enrollment of nearly 30,000 patients. The Phase 3 program includes 14 trials to evaluate evolocumab 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; as well as the administration of evolocumab (THOMAS-1 and THOMAS-2). Five studies in the evolocumab 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 evolocumab in combination with statin therapy compared to placebo and statin therapy reduces recurrent cardiovascular events in approximately 22,500 patients with cardiovascular disease; DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) in patients with hyperlipidemia at risk for cardiovascular disease; 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 evolocumab 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 evolocumab on LDL-C in patients with severe familial hypercholesterolemia. About Amgen's Commitment to Cardiovascular Disease Amgen is dedicated to addressing important scientific questions in order to advance care and improve the lives of patients with cardiovascular disease. Through its own research and development efforts and innovative partnerships, Amgen has built a robust cardiology 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. About Amgen Canada As a leader in innovation, Amgen Canada understands the value of science. With main operations located in Mississauga, Ont.'s vibrant biomedical cluster, and its research facility in Burnaby, B.C., Amgen Canada has been an important contributor to advancements in science and innovation in Canada since 1991. The company contributes to the development of new therapies or new uses for existing medicines in partnership with many of Canada's leading health-care, academic, research, government and patient organizations. To learn more about Amgen Canada, visit www.amgen.ca. Forward-Looking Statements This news release contains forward-looking statements that are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. 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Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we and our partners routinely obtain patents for products and technology, the protection of our products offered by patents and patent applications may be challenged, invalidated or circumvented by our competitors and there can be no guarantee of our or our partners' ability to obtain or maintain patent protection for our products or product candidates. We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products. Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates. Further, the discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to integrate the operations of companies we have acquired may not be successful. The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by Health Canada, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. # # # References 1. Amgen Data on File, Investigator Brochure. 2. World Health Organization. Quantifying Selected Major Risks to Health. In: The World Health Report 2002 - Reducing Risks, Promoting Healthy Life. Chapter 4: Geneva: World. 3. Merck Manuals website. http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/lipid_disorders/dyslipidemia.html. Accessed March 2014. 4. Statistics Canada. The Canadian Health Measures Survey. http://www.statcan.gc.ca/pub/82-625-x/2010001/article/11136-eng.htm Accessed March 2014. 5. Heart and Stroke Foundation of Canada http://www.heartandstroke.com/site/c.ikIQLcMWJtE/b.3484027/k.8419/Heart_disease__High_blood_cholesterol.htm Accessed March 2014. 6. National Human Genome Research Institute. Learning About Familial Hypercholesterolemia.http://www.genome.gov/25520184. Accessed March 2014. 7. World Health Organization. Familial Hypercholesterolaemia Report 1998. 8. Nordestgaard BG. et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Eur Heart J. 2013;34:3478-3490. 9. Abifadel M et al. Nat Genet. 2003;34:154-156. SOURCE Amgen Canada CONTACT: Natasha Bond Amgen Canada 905-285-3007 firstname.lastname@example.org Mary-Anne Cedrone Hill + Knowlton Strategies 416-413-4575 email@example.com To view this news release in HTML formatting, please use the following URL: http://www.newswire.ca/en/releases/archive/March2014/31/c7724.html CO: Amgen Canada ST: Ontario NI: BTC ECOSURV HEA -0- Mar/31/2014 11:00 GMT
New detailed data from three phase 3 pivotal studies show Amgen's novel investigational cholesterol-lowering medicine evolocumab
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