BRILINTA PEGASUS-TIMI 54 STUDY


PEGASUS-TIMI 54 STUDY SHOWS THAT LONG-TERM TREATMENT WITH BRILINTA REDUCED
THROMBOTIC CARDIOVASCULAR EVENTS IN PATIENTS WITH A HISTORY OF HEART ATTACK

Data from 21,000 patient study presented at American College of Cardiology 64th
Annual Scientific Session and simultaneously published in New England Journal of
Medicine

AstraZeneca on Saturday announced full results from the PEGASUS-TIMI 54 study, a
large-scale outcomes trial that investigated BRILINTA® (ticagrelor) tablets plus
low dose aspirin, compared to placebo plus low dose aspirin, for the chronic
secondary prevention of atherothrombotic events in patients who had experienced
a heart attack one to three years prior to study enrolment.

Key findings:

  · Both 90mg and 60mg study doses of ticagrelor with aspirin significantly
reduced the primary composite endpoint of cardiovascular (CV) death, myocardial
infarction (MI) or stroke compared to placebo.
  · As expected with an oral antiplatelet and consistent with studies in similar
patient populations, TIMI Major Bleeding1, the study's primary safety endpoint,
was higher with both doses of ticagrelor plus aspirin compared to placebo plus
aspirin. Importantly, the rates of intracranial haemorrhage (bleeding within the
skull) and fatal bleeding were low and were similar between study groups and the
placebo arm.

The data were presented during the opening late-breaking clinical trial session
of the American College of Cardiology's 64th Annual Scientific Session and Expo,
and also simultaneously published in the New England Journal of
Medicine (http://www.nejm.org/doi/full/10.1056/NEJMoa1500857?query=featured_home
) 
online.

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases,
Global Medicines Development, AstraZeneca, said: "As a company we are committed
to furthering cardiovascular research and are proud to have delivered the
PEGASUS-TIMI 54 study, AstraZeneca's largest clinical trial, involving more than
21,000 patients worldwide. Building on the landmark PLATO trial in acute
coronary syndrome, the positive PEGASUS study adds to the body of evidence for
BRILINTA and is the first prospective trial to evaluate longer term dual
antiplatelet therapy in higher risk patients with a history of a heart attack."

"We have just submitted regulatory filings to the European Medicines Agency and
the US Food and Drug Administration and we look forward to working with these
agencies towards a potential new indication in major markets."

Recent research has shown that one in five patients will have a further heart
attack, stroke or CV death in the subsequent three years following a heart
attack, even if patients were event free after 12 months2. For patients more
than one year on from a heart attack, the current standard of care is aspirin
alone. The PEGASUS-TIMI 54 study was designed to investigate the effect of
adding ticagrelor at 60mg and 90mg to low dose aspirin on reducing the risk of
CV death, heart attack or stroke in patients aged 50 and older with a history of
heart attack and one additional CV risk factor.

Efficacy Findings

In this trial, both study doses of ticagrelor significantly reduced the primary
endpoint of CV death, MI or stroke compared to placebo. The rates at 3 years
were 7.85% in the ticagrelor 90mg arm, 7.77% in the ticagrelor 60mg arm, and
9.04% in the placebo arm (Hazard Ratio (HR) for ticagrelor 90mg vs placebo 0.85,
95% CI 0.75 - 0.96, P=0.0080; HR for ticagrelor 60mg vs placebo 0.84, 95% CI
0.74 - 0.95, P=0.0043).

The effect of ticagrelor on each of the components of the primary endpoint was
consistent. A numerical decrease in the secondary endpoints of cardiovascular
death and all cause mortality was observed, but did not reach statistical
significance.

In addition, the primary efficacy endpoint of both doses of ticagrelor appeared
consistent across major subgroups including age, sex, index MI type
(STEMI/NSTEMI), time from qualifying MI, diabetes, aspirin dose, history of
percutaneous intervention (angioplasty), and geographical region.

Safety Findings

As expected, TIMI Major bleeding was higher with both doses of ticagrelor
compared to placebo, with rates at 3 years of 2.60% in the ticagrelor 90mg arm,
2.30% in the ticagrelor 60mg arm, and 1.06% in the placebo arm (HR for
ticagrelor 90mg vs placebo 2.69, 95% CI 1.96 - 3.70, p<0.001; HR for ticagrelor
60mg vs placebo 2.32, 95% CI 1.68 - 3.21, p<0.001).

However, the rates of fatal bleeding or intracranial haemorrhage were low and
similar between treatment arms.

Fatal bleeding rates at 3 years were 0.11% in the ticagrelor 90mg arm, 0.25% in
the ticagrelor 60mg arm, and 0.26% in the placebo arm (HR for ticagrelor 90mg vs
placebo 0.58, 95% CI 0.22 - 1.54, p=0.27; HR for ticagrelor 60mg vs placebo
1.00, 95% CI 0.44 - 2.27, p=1.00).

Intracranial haemorrhage rates at 3 years were 0.56% in the ticagrelor 90mg arm,
0.61% in the ticagrelor 60mg arm, and 0.47% in the placebo arm (HR for
ticagrelor 90mg vs placebo 1.44, 95% CI 0.83 - 2.49, p=0.19; HR for ticagrelor
60mg vs placebo 1.33, 95% CI 0.77 - 2.31, p=0.31).

The PEGASUS-TIMI 54 study, AstraZeneca's largest outcomes trials involving more
than 21,000 patients from over 1,100 sites in 31 countries, is part of the
PARTHENON programme. The PLATO study, involving over 18,000 patients, was the
first study in the programme and is the basis on which ticagrelor has been
approved in over 100 countries and included in 12 major ACS treatment guidelines
globally. Further ongoing PARTHENON studies are assessing ticagrelor for the
prevention of cardiovascular events in patients with peripheral arterial
disease, ischaemic stroke or transient ischaemic attack, and in patients with
diabetes and coronary atherosclerosis.

BRILINTA is not approved for secondary prevention of atherothrombotic events in
patients with a history of heart attack beyond one year or for the prevention of
cardiovascular events in patients with peripheral arterial disease, stroke,
diabetes or atherosclerosis.

1 TIMI Major Bleeding Classification:

  · Any intracranial bleeding, or
  · Clinically overt signs of haemorrhage associated with a drop in hemoglobin
(Hgb) of ≥5 g/dL (or, when hemoglobin is not available, a fall in hematocrit of
≥15%), or
  · Fatal bleeding (a bleeding event that directly led to death within 7 days).

2 Rapsomaniki E, Thuresson M, Yang E, et al. International comparison of
outcomes among 140,880 patients stable after acute MI; real world evidence from
electronic health and administrative records. Presented at European Society of
Cardiology Congress, Barcelona, Spain; 30 August - 3 September 2014.

About PEGASUS-TIMI 54
PEGASUS-TIMI 54 (PrEvention with TicaGrelor of SecondAry Thrombotic Events in
High-RiSk Patients with Prior AcUte Coronary Syndrome - Thrombolysis In
Myocardial Infarction Study Group) is one of AstraZeneca's largest ever outcomes
trials with more than 21,000 patients from over 1,100 sites in 31 countries in
Europe, the Americas, Africa and Australia/Asia. It was conducted in
collaboration with the Thrombolysis in Myocardial Infarction (TIMI) Study Group
from Brigham and Women's Hospital (Boston, MA, USA).

About BRILINTA®
BRILINTA is a direct-acting, selective and reversibly binding P2Y12 receptor
antagonist in a chemical class called cyclo-pentyl-triazolo-pyrimidines (CPTPs).
BRILINTA works by inhibiting platelet activation.

BRILINTA (90mg) 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]). BRILINTA has been
shown to reduce the rate of a combined end point of CV death, MI, or stroke
compared to clopidogrel. The difference between treatments was driven by CV
death and MI with no difference in stroke. In patients treated with percutaneous
coronary intervention, it also reduces the rate of stent thrombosis.

BRILINTA is a registered trademark of the AstraZeneca group.

About the Thrombolysis in Myocardial Infarction (TIMI) Study Group
The TIMI Study Group is affiliated with Brigham and Women's Hospital and Harvard
Medical School and is located in Boston, Massachusetts. It is one of the oldest
cardiovascular academic research organisation in the United States and has
conducted numerous practice-changing clinical trials in patients with CV disease
or risk factors for CV disease.

About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialisation 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

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16 March 2015

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