New detailed data from three phase 3 pivotal studies show Amgen's novel investigational cholesterol-lowering medicine evolocumab

 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. 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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 natasha.bond@amgen.com   Mary-Anne Cedrone Hill + Knowlton Strategies 416-413-4575  mary-anne.cedrone@hkstrategies.ca  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