AstraZeneca Announces Progress on Global PARTHENON Clinical Trial Program with BRILINTA (ticagrelor) in High-Risk Cardiovascular

  AstraZeneca Announces Progress on Global PARTHENON Clinical Trial Program
  with BRILINTA (ticagrelor) in High-Risk Cardiovascular Disease Patient
  Populations in Advance of American College of Cardiology Scientific Session

   Enrollment completed for EUCLID study in patients with Peripheral Artery
                                   Disease

         United States recruitment has begun for SOCRATES and THEMIS

Business Wire

WILMINGTON, Del. -- March 17, 2014

AstraZeneca (NYSE: AZN) today announced it has completed patient enrollment
approximately four months ahead of plan in the Phase III clinical trial EUCLID
studying BRILINTA^® (ticagrelor) tablets. Part of PARTHENON, AstraZeneca’s
largest clinical trial program, EUCLID has randomized more than 13,500
patients globally with peripheral artery disease (PAD); approximately 20
percent are patients in the United States (US) from more than 300 active
clinical trial sites across the country. EUCLID is designed to evaluate the
effects of ticagrelor (monotherapy) compared to clopidogrel (monotherapy) on
cardiovascular (CV) events and safety in PAD patients. Ticagrelor is currently
not approved for the treatment of patients with PAD.

“We are very excited to have completed enrollment in the EUCLID study ahead of
schedule. This study will provide important information regarding the use of
oral antiplatelet agents in peripheral artery disease,” said EUCLID study
chair William Hiatt, MD, Professor of Medicine, Division of Cardiology,
University of Colorado School of Medicine and CPC Clinical Research. “PAD
affects approximately 202 million people globally and 8.5 million people in
the US. Patients living with the disease are at high risk for developing
myocardial infarctions, strokes, and other health complications.”

AstraZeneca also announced today that US recruitment and enrollment is
underway in two additional Phase III PARTHENON studies – SOCRATES and THEMIS.
SOCRATES (AcuteStrokeOr Transient IsChaemic Attack TReated  withAspirin
orTicagrelor and Patient OutcomES) will evaluate the efficacy of ticagrelor
compared to aspirin in reducing major vascular events in patients with acute
ischemic stroke or transient ischemic attack (TIA). BRILINTA is currently not
approved for the treatment of patients with ischemic stroke or TIA. THEMIS
(Effect of Ticagrelor on Health Outcomes in DiabEtes Mellitus Patients
Intervention Study) will evaluate the efficacy of ticagrelor vs placebo, on
top of standard of care including aspirin, for the long-term prevention of
major vascular events in patients with Type 2 diabetes and coronary
atherosclerosis. ^ BRILINTA is not currently approved for the prevention of CV
events in patients with diabetes and coronary atherosclerosis.

“Even with aspirin, more than 10 percent of patients who have had an acute
ischemic stroke or transient ischemic attack will have a subsequent major
stroke within 90 days. We strongly encourage physicians to refer appropriate
patients for enrollment in the SOCRATES clinical trial, which will be
investigating whether the use of ticagrelor in this patient population can
help address a substantial unmet need,” said SOCRATES study co-chair Clay
Johnston, MD, PhD, Director, Clinical and Translational Science Institute,
Associate Vice Chancellor of Research, University of California, San Francisco
(UCSF).

“Of the approximately 26 million people in the US who suffer from diabetes,
over 90 percent have Type 2 diabetes – and nearly two-thirds of them will die
from cardiovascular disease,” ^ said THEMIS study co-chair Deepak L. Bhatt,
MD, MPH, Executive Director of Interventional Cardiovascular Programs, Brigham
and Women’s Hospital Heart and Vascular Center, and Professor of Medicine at
Harvard Medical School. “The THEMIS study will explore the use of ticagrelor
in patients with diabetes, and hopes to provide new scientific evidence to
guide appropriate treatment for these high-risk patients, with all of their
associated comorbidities.”

“We really value our collaborations with these top academic institutions and
clinician-scientists leading the studies that may add substantially to our
scientific understanding of appropriate treatment across the spectrum of
atherosclerotic disease – including PAD, stroke and diabetes,” said James
Ferguson, MD, Vice President, Cardiovascular Therapeutic Area, US Medical
Affairs, AstraZeneca. “AstraZeneca is fully committed to broader exploration
of the potential for BRILINTA in these additional high-risk clinical
circumstances.”

EUCLID, SOCRATES, and THEMIS each have an Independent Data Monitoring
Committee, which will review the safety and efficacy of treatments in these
trials. The trials will be conducted in accordance with Good Clinical
Practice.

SOCRATES and THEMIS Now Enrolling

SOCRATES is designed to randomize 9,600 patients globally who have experienced
an acute ischemic stroke or TIA, with approximately 200 US clinical trial
sites planned. It is a randomized, parallel group study evaluating the
efficacy of ticagrelor compared to aspirin in reducing major CV events,
defined as the composite of all-cause mortality, myocardial infarction (MI),
and stroke in this patient population. Men or women 40 years of age or older
who have experienced either acute ischemic stroke or high-risk TIA may qualify
for randomization in this trial within 24 hours after onset of symptoms.
Additional information about SOCRATES trial sites and/or patient enrollment is
available at www.clinicaltrials.gov by searching under the term SOCRATES or by
contacting ClinicalTrialTransparency@astrazeneca.com.

THEMIS is designed to randomize 17,000 patients globally, with approximately
250 US clinical trial sites planned. It is an event-driven, randomized,
parallel group study evaluating the efficacy of long-term treatment with
ticagrelor compared with placebo for the prevention of major CV events,
defined as the composite of CV death, MI, or stroke with Type 2 diabetes,
without a history of previous MI or stroke but with documented coronary
atherosclerosis. Men or women 50 years of age or older with Type 2 diabetes
who have been on treatment with a glucose-lowering medication for at least six
months, and have either documented coronary artery occlusive disease or
previous revascularization of a coronary artery, may qualify for participation
in this trial. Additional information about THEMIS trial sites and/or patient
enrollment is available at www.clinicaltrials.gov by searching under the term
THEMIS or by contacting THEMIS-RD@astrazeneca.com.

Interested physicians may also visit the AstraZeneca Cardiovascular Research
booth (#3407) at the 2014 Annual American College of Cardiology Scientific
Session in Washington, DC on March 29–31.

About EUCLID

EUCLID (Examining Use of tiCagreLor In paD) recruited more than 13,500
patients globally, including patients from more than 300 active US clinical
trial sites. It is a randomized, double-blind, parallel group, multi-center
study evaluating the efficacy of ticagrelor (monotherapy) compared to
clopidogrel (monotherapy) in reducing the primary endpoint – a composite of CV
death, MI, or ischemic stroke – in patients with PAD. BRILINTA is currently
not approved for the treatment of patients with PAD.

About PARTHENON

AstraZeneca is currently collaborating with over 4,000 clinical investigators
in more than 30 countries as part of the PARTHENON program, and has
established partnerships with a number of pre-eminent research institutions.
In addition to EUCLID, SOCRATES and THEMIS, PEGASUS-TIMI 54 is another ongoing
global study evaluating ticagrelor for the secondary prevention of CV events
in patients with previous MI.

BRILINTA is currently not approved for the treatment of patients with ischemic
stroke, TIA, PAD, for the prevention of CV events in patients with diabetes
and coronary atherosclerosis, or for secondary prevention in patients with a
history of previous MI.

Approved Use for BRILINTA (ticagrelor) tablets

BRILINTA is indicated to reduce the rate of thrombotic CV events in patients
with ACS (unstable angina [UA], non–ST-elevation myocardial infarction
[NSTEMI], or ST-elevation myocardial infarction [STEMI]). In PLATO, BRILINTA
has been shown to reduce the rate of a combined end point of CV death, MI, or
stroke compared to clopidogrel. In PLATO, the difference between treatments
was driven by CV death and MI with no difference in stroke. In patients
treated with an artery-opening procedure known as percutaneous coronary
intervention (PCI), BRILINTA reduces the rate of stent thrombosis.

BRILINTA has been studied in ACS in combination with aspirin. Maintenance
doses of aspirin above 100 mg decreased the effectiveness of BRILINTA. Avoid
maintenance doses of aspirin above 100 mg daily.

IMPORTANT SAFETY INFORMATION ABOUT BRILINTA

WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

A. BLEEDING RISK

  *BRILINTA, like other antiplatelet agents, can cause significant, sometimes
    fatal, bleeding
  *Do not use BRILINTA in patients with active pathological bleeding or a
    history of intracranial hemorrhage
  *Do not start BRILINTA in patients planned to undergo urgent coronary
    artery bypass graft surgery (CABG). When possible, discontinue BRILINTA at
    least 5 days prior to any surgery
  *Suspect bleeding in any patient who is hypotensive and has recently
    undergone coronary angiography, percutaneous coronary intervention (PCI),
    CABG, or other surgical procedures in the setting of BRILINTA
  *If possible, manage bleeding without discontinuing BRILINTA. Stopping
    BRILINTA increases the risk of subsequent cardiovascular events

B. ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

  *Maintenance doses of aspirin above 100 mg reduce the effectiveness of
    BRILINTA and should be avoided. After any initial dose, use with aspirin
    75 mg - 100 mg per day

CONTRAINDICATIONS

  *BRILINTA is contraindicated in patients with a history of intracranial
    hemorrhage and active pathological bleeding such as peptic ulcer or
    intracranial hemorrhage. BRILINTA is contraindicated in patients with
    severe hepatic impairment because of a probable increase in exposure; it
    has not been studied in these patients. Severe hepatic impairment
    increases the risk of bleeding because of reduced synthesis of coagulation
    proteins. BRILINTA is also contraindicated in patients with
    hypersensitivity (e.g., angioedema) to ticagrelor or any component of the
    product

WARNINGS AND PRECAUTIONS

  *Moderate Hepatic Impairment: Consider the risks and benefits of treatment,
    noting the probable increase in exposure to ticagrelor
  *Premature discontinuation increases the risk of MI, stent thrombosis, and
    death
  *Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of
    patients taking clopidogrel. Dyspnea resulting from BRILINTA is
    self-limiting. Rule out other causes
  *BRILINTA is metabolized by CYP3A4/5. Avoid use with strong CYP3A
    inhibitors and potent CYP3A inducers. Avoid simvastatin and lovastatin
    doses >40 mg
  *Monitor digoxin levels with initiation of, or any change in, BRILINTA
    therapy

ADVERSE REACTIONS

  *The most commonly observed adverse reactions associated with the use of
    BRILINTA vs clopidogrel were Total Major Bleeding (11.6% vs 11.2%) and
    dyspnea (14% vs 8%)
  *In clinical studies, BRILINTA has been shown to increase the occurrence of
    Holter-detected bradyarrhythmias. PLATO excluded patients at increased
    risk of bradycardic events. Consider the risks and benefits of treatment

Please read full Prescribing Information, including Boxed WARNINGS, and
Medication Guide.

You are encouraged to report negative side effects of prescription drugs to
the FDA. Visit www.fda.gov/safety/medwatch or call 1-800-FDA-1088.

Patients can find out more information about BRILINTA at
www.BRILINTAtouchpoints.com  or by calling 1-888-412-7454.

AstraZeneca offers the AZ&Me^TM Prescription Savings Program. To determine
eligibility, patients can visit www.AZandMe.com or call 1-800-AZandMe
(292-6363).

NOTES TO EDITORS

About BRILINTA^® (ticagrelor) tablets

BRILINTA is an oral antiplatelet treatment for ACS. BRILINTA is a
direct-acting P2Y[12] receptor antagonist in a chemical class called
cyclopentyltriazolopyrimidines (CPTPs). BRILINTA works by inhibiting platelet
activation and has been shown to reduce the rate of thrombotic CV events, such
as a heart attack or CV death, in patients with ACS.

BRILINTA is a registered trademark of the AstraZeneca group of companies.

About PLATO

PLATO (PLATelet Inhibition and Patient Outcomes) was a large (18,624 patients
in 43 countries), head-to-head patient outcomes study of BRILINTA vs
clopidogrel, both given in combination with aspirin and other standard
therapy. The study was designed to establish whether BRILINTA could achieve a
clinically meaningful reduction in cardiovascular (CV) events in acute
coronary syndrome (ACS) patients, above and beyond that afforded by
clopidogrel. Patients were treated for at least six months and up to 12
months.

PLATO demonstrated that treatment with BRILINTA led to a significantly greater
reduction in the primary end point – a composite of CV death, MI (excluding
silent MI), or stroke – compared to patients who received clopidogrel (9.8% vs
11.7% at 12 months; 1.9% absolute risk reduction [ARR]; 16% relative risk
reduction [RRR]; 95% CI, 0.77 to 0.92; P<0.001). The difference in treatments
was driven by CV death and MI with no difference in stroke. In PLATO, the
absolute difference in treatment benefit vs clopidogrel was seen at 30 days
and the Kaplan-Meier survival curves continued to diverge throughout the
12-month treatment period.

The PLATO study also demonstrated that treatment with BRILINTA for 12 months
was associated with a 21% RRR in CV death (4% vs 5.1%; 1.1% ARR; P=0.001) and
a 16% RRR in MI (excluding silent MI) compared to clopidogrel at 12 months
(5.8% vs 6.9%; 1.1% ARR; P<0.005).

The primary safety end point in the PLATO study was Total Major Bleeding,
which includes Fatal and Life-threatening bleeding, (11.6% for BRILINTA and
11.2% for clopidogrel) at 12 months. In PLATO, Non-CABG-related major + minor
bleeding events were more common with BRILINTA vs clopidogrel (8.7% vs 7%
respectively). The rate of non-CABG-related major bleeding was higher for
BRILINTA (4.5%) vs clopidogrel (3.8%). The PLATO trial did not show an
advantage for BRILINTA compared with clopidogrel for CABG-related Bleeding
(Total Major 85.8% vs 86.9% and Fatal/Life-threatening 48.1% vs 47.9%,
respectively).

Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of
patients treated with clopidogrel. Dyspnea was usually mild to moderate in
intensity and often resolved during continued treatment.

*PLATO used the following bleeding severity categorization:Major
Bleed–Fatal/Life-threatening. Any one of the following: fatal; intracranial;
intrapericardial bleed with cardiac tamponade; hypovolemic shock or severe
hypotension due to bleeding and requiring pressors or surgery; clinically
overt or apparent bleeding associated with a decrease in hemoglobin (Hb) of
more than 5 g/dL; transfusion of 4 or more units (whole blood or packed red
blood cells [PRBCs]) for bleeding.Major Bleed–Other. Any one of the
following: significantly disabling (e.g., intraocular with permanent vision
loss); clinically overt or apparent bleeding associated with a decrease in Hb
of 3 g/dL; transfusion of 2-3 units (whole blood or PRBCs) for bleeding.Minor
Bleed. Requires medical intervention to stop or treat bleeding (e.g.,
epistaxis requiring visit to medical facility for packing).Minimal Bleed. All
others (e.g., bruising, bleeding gums, oozing from injection sites, etc.) not
requiring intervention or treatment.

About Acute Coronary Syndrome (ACS)

ACS is an umbrella term for conditions that result from insufficient blood
supply to the heart muscle. These conditions include unstable angina (UA),
non–ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial
infarction (STEMI). The conditions are defined by ECG changes and heart muscle
enzyme leakage. Non–ST-elevation acute coronary syndrome (NSTE-ACS) includes
unstable angina (UA) and non–ST-elevation myocardial infarction (NSTEMI); the
term is usually used before heart muscle enzymes have been analyzed.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development, and commercialization of prescription
medicines, primarily for the treatment of cardiovascular, metabolic,
respiratory, inflammation, autoimmune, oncology, infection, and neuroscience
diseases. AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more information
please visit:www.astrazeneca.com.

2958805 3/14

Contact:

AstraZeneca
Media Inquiries US
Michele Meixell, +1 302-885-6351
michele.meixell@astrazeneca.com
or
Stephanie Jacobson, +1 302-885-5924
stephanie.jacobson@astrazeneca.com
or
Investor Inquiries US
Colleen Proctor, +1 302-357-4882
colleen.proctor@astrazeneca.com
or
Karl Hard, +44 20 7604 8123
karl.j.hard@astrazeneca.com
or
Anthony Brown, +44 20 7604 8067
anthony.brown@astrazeneca.com
or
Jens Lindberg, +44 20 7604 8414
jens.lindberg@astrazeneca.com
 
Press spacebar to pause and continue. Press esc to stop.