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. All statements, other than statements of 
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prescriber patterns or practices, reimbursement activities and outcomes and 
other such estimates and results. Forward-looking statements involve 
significant risks and uncertainties, including those discussed below and more 
fully described in the Securities and Exchange Commission (SEC) reports filed 
by Amgen, including Amgen's most recent annual report on Form 10-K and any 
subsequent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen's 
most recent Forms 10-K, 10-Q and 8-K for additional information on the 
uncertainties and risk factors related to our business. Unless otherwise 
noted, Amgen is providing this information as of March 30, 2014, and expressly 
disclaims any duty to update information contained in this news release.

No forward-looking statement can be guaranteed and actual results may differ 
materially from those Amgen Inc. and its subsidiaries (which are collectively 
referred to as we, or us) project. Discovery or identification of new product 
candidates or development of new indications for existing products cannot be 
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there can be no guarantee that any particular product candidate or development 
of a new indication for an existing product will be successful and become a 
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# # #

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 
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