PEGASUS-TIMI 54 Study of BRILINTA® Meets Primary Endpoint in Both 60mg and 90mg Doses

AstraZeneca (NYSE:AZN) today announced that the PEGASUS-TIMI 54 study, a large scale outcomes trial involving over 21,000 patients, successfully met its primary efficacy endpoint. The study assessed BRILINTA® (ticagrelor) tablets at either 60mg twice daily or 90mg twice daily plus low-dose aspirin for the secondary prevention of atherothrombotic events in patients who had experienced a heart attack one to three years prior to study start. The primary efficacy endpoint was a composite of cardiovascular (CV) death, myocardial infarction (MI) or stroke.

Preliminary analysis did not reveal any unexpected safety issues. Full evaluation of the data is ongoing.

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca, said: “We are very pleased with the top line results of the PEGASUS-TIMI 54 study, the second positive major outcomes study in the PARTHENON program. The results build on existing understanding of the benefits of BRILINTA for patients with acute coronary syndrome and offer important clinical insights into its potential role for the longer term prevention of cardiovascular events. We look forward to presenting the data later this year.”

The PEGASUS-TIMI 54 study investigated two different doses of ticagrelor on a background of low dose aspirin versus placebo plus low dose aspirin, in patients aged 50 and older with a history of heart attack and one additional CV risk factor. The study was designed to better understand the management of patients more than 12 months after their heart attack, who remain at high risk for major thrombotic events.

Complete results from the PEGASUS-TIMI 54 study will be submitted to a scientific meeting in 2015 and pending further analysis, AstraZeneca plans to file this data with regulatory health authorities.

The PEGASUS-TIMI 54 study is part of AstraZeneca’s PARTHENON program. The PLATO study, involving over 18,000 ACS patients, was the first study in the program 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 investigating 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 PAD, stroke, diabetes or atherosclerosis.

BRILINTA (90mg) is indicated to reduce the rate of thrombotic cardiovascular (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, myocardial infarction (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 (PCI), it also reduces the rate of stent thrombosis.

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

IMPORTANT SAFETY INFORMATION ABOUT BRILINTA (ticagrelor)

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.

NOTES TO EDITORS

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 the PARTHENON Program

The PEGASUS-TIMI 54 study is part of PARTHENON, the clinical trial program for BRILINTA and the largest ever AstraZeneca clinical trial program. PARTHENON involves nearly 80,000 patients at high risk of cardiovascular events (MI, stroke and/or cardiovascular death) due to their underlying disease and

aims to enhance scientific understanding of the role of ticagrelor in the treatment of atherothrombotic conditions. It includes five key studies covering broad patient populations across varying timescales. The studies are investigating a wide range of cardiovascular disorders, including stroke/transient ischaemic attack (SOCRATES), peripheral arterial disease (EUCLID) and patients with type 2 diabetes at high risk of cardiovascular events (THEMIS).

The PARTHENON program seeks to obtain four potential new indications for ticagrelor over the next 4 years.

About BRILINTA®

BRILINTA is a direct-acting P2Y12 receptor antagonist in a chemical class called cyclo-pentyl-triazolo-pyrimidines (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 acute coronary syndrome (ACS).

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 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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