Data From Phase 3 Pivotal Studies Show Amgen's Novel Investigational Cholesterol-Lowering Medication Evolocumab Significantly

 Data From Phase 3 Pivotal Studies Show Amgen's Novel Investigational  Cholesterol-Lowering Medication Evolocumab Significantly Reduced LDL  Cholesterol in Statin Intolerant Patients and in Patients on Statins  Data From Two Separate Phase 3 Studies of Evolocumab (AMG 145), a PCSK9  Inhibitor, Presented in Late-Breaking Clinical Trials Session at ACC.14  Data Presented at ACC.14 From Five Phase 3 Studies in More Than 4,000 Patients  Form the Basis of Global Filing Plan  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 two Phase 3 pivotal studies that showed treatment with its  novel investigational cholesterol-lowering medication, evolocumab (AMG 145),  resulted in a statistically significant reduction in low-density lipoprotein  cholesterol (LDL-C) between 37-39 per cent, compared to ezetimibe in patients  with high cholesterol who cannot tolerate statins (GAUSS-2) and between 55-76  per cent compared to placebo when used in combination with statin therapy in  patients with high cholesterol (LAPLACE-2). Results from the two separate  Phase 3 studies, GAUSS-2 and LAPLACE-2, were presented as Late-Breaking  Clinical Trials and complement the three Phase 3 studies presented as Featured  Clinical Research at the American College of Cardiology's 63(rd) Annual  Scientific Session (ACC.14).  Positive results from the GAUSS-2 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)  In the GAUSS-2 study, the most common adverse events (AEs) (≥5 per cent in  the combined evolocumab group) were headache, myalgia, pain in extremity and  muscle spasms. In the LAPLACE-2 study, no AEs occurred in ≥ 2 per cent of  the evolocumab combined group. The most common AEs in the evolocumab combined  group (>1.5 per cent) were back pain, arthralgia, headache, muscle spasms and  pain in extremity.  "As treatment with statins continues to be an important tool in the management  of high cholesterol, we are encouraged by the positive data from the Phase 3  studies of evolocumab in patients with statin intolerance and in patients  already on statin therapy," said Sean E. Harper, M.D., executive vice  president of Research and Development at Amgen. "We hope that evolocumab will  be able to help patients who are on a moderate or high-intensity statin and  not adequately controlled, as well as patients who cannot tolerate statins and  are in need of an alternate treatment option to help lower their LDL  cholesterol levels."  "Results from the five Phase 3 pivotal studies that we presented at ACC span  more than 4,000 patients and provide us with important insights on the  potential of evolocumab as a treatment for a range of patients at-risk for  cardiovascular disease," Harper added. "We are working closely with regulatory  authorities on our global filing plan in hopes of bringing this new treatment  option to patients with dyslipidemia."  GAUSS-2 (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin to  Intolerant Subjects-2) Primary Results        --  The GAUSS-2 study showed that in 307 patients with high         cholesterol who could not tolerate effective doses of at least         two different statins due to muscle-related side effects,         treatment with subcutaneous evolocumab (140 mg every two weeks         or 420 mg monthly), significantly reduced mean LDL-C by 37-39         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 37 per cent for           evolocumab 140 mg every two weeks and 39 per cent for           evolocumab 420 mg monthly compared to ezetimibe.         o At week 12, the per cent reduction from baseline in LDL-C was           38 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 (> 5 per cent in evolocumab combined group)         were headache (7.8 per cent evolocumab; 8.8 per cent         ezetimibe), myalgia (7.8 per cent evolocumab; 17.6 per cent         ezetimibe), pain in extremity (6.8 per cent evolocumab; 1.0 per         cent ezetimibe) and muscle spasms (6.3 per cent evolocumab; 3.9         per cent ezetimibe).  LAPLACE-2 (LDL-C Assessment with PCSK9 MonoclonaL Antibody Inhibition Combined  with Statin ThErapy-2) Primary Results     --  The LAPLACE-2 study showed that in 1,896 patients with high         cholesterol (LDL-C > 2.1 mmol/L), treatment with subcutaneous         evolocumab (140 mg every two weeks or 420 mg monthly) in         combination with different daily doses of statin therapy         significantly reduced mean LDL-C by 55-76 per cent from         baseline compared to placebo and 38-47 per cent from baseline         compared to ezetimibe (p<0.001).         o Results of the study showed the mean reduction in LDL-C from           baseline at weeks 10 and 12 was between 66-75 per cent for           evolocumab 140 mg every two weeks versus placebo and between           38-45 per cent versus ezetimibe, for all statin cohorts.         o Results of the study also showed the mean per cent reduction           in LDL-C from baseline at weeks 10 and 12 was between 63-75           per cent for evolocumab 420 mg monthly versus placebo and 44           per cent versus ezetimibe, for all statin cohorts.         o At week 12, the per cent reduction from baseline in LDL-C was           between 68-76 per cent for evolocumab 140 mg every two weeks           and between 55-71 per cent for evolocumab 420 mg monthly,           compared to placebo, for all statin cohorts. Compared with           ezetimibe, evolocumab reduced LDL-C from baseline between           40-47 per cent when dosed every two weeks and between 39-41           per cent when dosed monthly, for all statin cohorts.     --  No AEs occurred in ≥ 2 per cent of the evolocumab         combined group. The most common AEs in the evolocumab combined         group were back pain (1.8 per cent evolocumab; 3.2 per cent         ezetimibe; 2.5 per cent placebo), arthralgia (1.7 per cent         evolocumab; 1.8 per cent ezetimibe; 1.6 per cent placebo),         headache (1.7 per cent evolocumab; 2.3 per cent ezetimibe; 2.7         per cent placebo), muscle spasms (1.5 per cent evolocumab; 2.7         per cent ezetimibe; 1.1 per cent placebo) and pain in extremity         (1.5 per cent evolocumab; 1.4 per cent ezetimibe; 1.3 per cent         placebo).  "Some patients being treated for increased cholesterol levels continue to  encounter cardiovascular issues," said Dr. Jacques Genest, Professor, Faculty  of Medicine at McGill University. "The results from the GAUSS-2 and LAPLACE-2  studies for evolocumab may offer a new lipid-lowering treatment option for  high-risk patients, or it may help patients control their LDL cholesterol  levels when their current treatments are not sufficient."  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)  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.  GAUSS-2 Study Design  GAUSS-2 (Goal Achievement After Utilizing an Anti-PCSK9  Antibody in Statin Intolerant Subjects-2) is a Phase 3 randomized,  multicenter, double-blind, placebo- and ezetimibe-controlled trial designed to  evaluate the safety, tolerability and efficacy of evolocumab in 307  hyperlipidemic patients who could not tolerate effective doses of at least two  different statins due to muscle-related side effects. Patients were randomized  to one of four treatment groups: subcutaneous evolocumab 140 mg every two  weeks and oral placebo daily; subcutaneous evolocumab 420 mg monthly and oral  placebo daily; subcutaneous placebo every two weeks and oral ezetimibe 10 mg  daily; or subcutaneous placebo monthly and oral 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. 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).  LAPLACE-2 Study Design LAPLACE-2 (LDL-C Assessment with PCSK9 MonoclonaL  Antibody Inhibition Combined with Statin ThErapy-2) is a Phase 3 randomized,  multicenter, double-blind, placebo- and ezetimibe-controlled study designed to  evaluate safety, tolerability and efficacy of evolocumab in 1,896 patients  with primary hypercholesterolemia and mixed dyslipidemia (LDL-C ≥ 2.1  mmol/L) when added to statin therapy. Patients were randomized to one of 24  treatment groups in a two-step randomization. Eligible patients were initially  randomized to one of five open label background statin treatments:  atorvastatin 10 mg, atorvastatin 80 mg, rosuvastatin 5 mg, rosuvastatin 40 mg  or simvastatin 40 mg daily. Patients randomized to atorvastatin were then  randomized to one of six treatment groups: evolocumab every two weeks and oral  placebo, evolocumab every month and oral placebo, subcutaneous placebo every  two weeks and oral placebo, subcutaneous placebo every month and oral placebo,  subcutaneous placebo every two weeks and ezetimibe 10 mg, or subcutaneous  placebo every month and ezetimibe 10 mg. Patients randomized to rosuvastatin  or simvastatin were then randomized to one of four treatment groups:  evolocumab every two weeks, evolocumab every month, subcutaneous placebo every  two weeks, or subcutaneous placebo every month.  The co-primary endpoints were the mean per cent change from baseline in LDL-C  at weeks 10 and 12 and the per cent change in LDL-C reduction at week 12.  Co-secondary efficacy endpoints included means at weeks 10 and 12 and at week  12 for the following: LDL-C < 1.8 mmol/L; absolute change from baseline in  LDL-C; 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.(6  )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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In addition, we compete with other companies with respect to some of  our marketed products as well as for the discovery and development of new  products. We believe that some of our newer products, product candidates or  new indications for existing products, may face competition when and as they  are approved and marketed. 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  Health Organization;202:47-97.  3. Merck Manuals website.  http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/lipi d_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. Abifadel M et al. Nat  Genet. 2003;34:154-156.       SOURCE  Amgen Canada  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/c1886.html  CO: Amgen Canada ST: Ontario NI: BTC  
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