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. 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. 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 
guaranteed and movement from concept to product is uncertain; consequently, 
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 
commercial product. Further, preclinical results do not guarantee safe and 
effective performance of product candidates in humans. The complexity of the 
human body cannot be perfectly, or sometimes, even adequately modeled by 
computer or cell culture systems or animal models. The length of time that it 
takes for us and our partners to complete clinical trials and obtain 
regulatory approval for product marketing has in the past varied and we expect 
similar variability in the future. We develop product candidates internally 
and through licensing collaborations, partnerships and joint ventures. Product 
candidates that are derived from relationships may be subject to disputes 
between the parties or may prove to be not as effective or as safe as we may 
have believed at the time of entering into such relationship. Also, we or 
others could identify safety, side effects or manufacturing problems with our 
products after they are on the market. Our business may be impacted by 
government investigations, litigation and product liability claims. If we fail 
to meet the compliance obligations in the corporate integrity agreement 
between us and the U.S. government, we could become subject to significant 
sanctions.  We depend on third parties for a significant portion of our 
manufacturing capacity for the supply of certain of our current and future 
products and limits on supply may constrain sales of certain of our current 
products and product candidate development.

In addition, sales of our products (including products of our wholly-owned 
subsidiaries) are affected by the reimbursement policies imposed by 
third-party payers, including governments, private insurance plans and managed 
care providers and may be affected by regulatory, clinical and guideline 
developments and domestic and international trends toward managed care and 
healthcare cost containment as well as legislation affecting pharmaceutical 
pricing and reimbursement. Government and others' regulations and 
reimbursement policies may affect the development, usage and pricing of our 
products. 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  
-0- Mar/31/2014 11:00 GMT
 
 
Press spacebar to pause and continue. Press esc to stop.