AstraZeneca PLC Wins FDA Green Light for Long-Term Brilinta Use in U.S.

WILMINGTON, Del., Sept. 3, 2015 /PRNewswire/ -- AstraZeneca today announced that the US Food and Drug Administration (FDA) has approved BRILINTA^® (ticagrelor) tablets at a new 60mg dose to be used in patients with a history of heart attack beyond the first year. With this expanded indication, BRILINTA is now approved to reduce the rate of cardiovascular death, myocardial infarction (MI also known as heart attack) and stroke in patients with acute coronary syndrome (ACS) or a history of MI.

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BRILINTA is an oral antiplatelet treatment that works by inhibiting platelet activation and was first approved by the FDA in July 2011 on the basis of data from the PLATO study. For at least the first 12 months following ACS, it is superior to clopidogrel and is the first and only FDA approved oral antiplatelet to demonstrate superior reductions in CV death vs clopidogrel. BRILINTA also reduces the rate of stent thrombosis in patients who have been stented for the treatment of ACS. In the management of ACS, the recommended maintenance dose of BRILINTA is 90mg twice daily during the first year after an ACS event. After one year, patients with a history of heart attack can now be treated with 60mg twice daily. BRILINTA should be used with a daily maintenance dose of aspirin of 75-100mg.

“We know that patients remain at risk beyond the first year after their heart attack,” said Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca. “Today’s approval provides an important new treatment option and underscores the role BRILINTA can play in reducing the risk of a subsequent cardiovascular event for patients both in the acute setting and in the longer term.”

The expanded indication for BRILINTA has been approved under FDA Priority Review, a designation granted to medicines that the FDA determines have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. The approval is based on the PEGASUS TIMI-54 study¹, a large-scale outcomes trial involving more than 21,000 patients. PEGASUS TIMI-54 investigated ticagrelor tablets plus low-dose aspirin, compared to placebo plus low-dose aspirin, for the long-term prevention of cardiovascular death, heart attack and stroke in patients who had experienced a heart attack one to three years prior to study enrollment.

“The PEGASUS-TIMI 54 trial demonstrated that the addition of ticagrelor to low-dose aspirin in patients with a prior heart attack significantly reduced the risk of dying from cardiovascular causes, having another heart attack, or having a stroke,” said Marc Sabatine, MD, MPH (Chairman, Thrombolysis in Myocardial Infarction [TIMI] Study Group, Brigham and Women’s Hospital, Boston, MA, USA and lead investigator for PEGASUS-TIMI 54). “While it’s important that physicians tailor their treatment approach for each patient, these data speak to the clinically important benefit that can be gained when adding ticagrelor to the current standard therapy in a patient population at increased risk for recurrent cardiovascular events in the long-term.”

Between PLATO and now PEGASUS, nearly 40,000 patients have been studied in clinical trials with BRILINTA. BRILINTA has been approved in over 100 countries and is included in 12 major ACS treatment guidelines globally. In the American Heart Association (AHA)/American College of Cardiology (ACC) 2014 NSTE-ACS Guideline, BRILINTA is preferred over clopidogrel for the maintenance treatment in NSTE-ACS patients (Class IIa) and is recommended as a treatment option in the management of NSTE-ACS patients (Class I).

The new BRILINTA 60mg tablet is expected to be available in pharmacies by the end of September 2015.

INDICATIONS
BRILINTA is indicated to reduce the rate of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction. For at least the first 12 months following ACS, it is superior to clopidogrel.

BRILINTA also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS.

DOSING
In the management of ACS, initiate BRILINTA treatment with a 180-mg loading dose. Administer 90 mg twice daily during the first year after an ACS event. After one year administer 60 mg twice daily. Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg.

IMPORTANT SAFETY INFORMATION FOR BRILINTA (ticagrelor) 60-MG AND 90-MG TABLETS

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 undergoing urgent coronary artery bypass graft surgery
• 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

CONTRAINDICATIONS

• BRILINTA is contraindicated in patients with a history of intracranial hemorrhage or active pathological bleeding such as peptic ulcer or intracranial hemorrhage. BRILINTA is also contraindicated in patients with hypersensitivity (eg, angioedema) to ticagrelor or any component of the product

WARNINGS AND PRECAUTIONS

• Dyspnea was reported in about 14% of patients treated with BRILINTA, more frequently than in patients treated with control agents. Dyspnea resulting from BRILINTA is often self-limiting
• Discontinuation of BRILINTA will increase the risk of MI, stroke, and death. When possible, interrupt therapy with BRILINTA for 5 days prior to surgery that has a major risk of bleeding. If BRILINTA must be temporarily discontinued, restart as soon as possible
• Avoid use of BRILINTA in patients with severe hepatic impairment. Severe hepatic impairment is likely to increase serum concentration of ticagrelor and there are no studies of BRILINTA in these patients

ADVERSE REACTIONS

• The most common adverse reactions associated with the use of BRILINTA included bleeding and dyspnea: In PLATO, for BRILINTA vs clopidogrel, non-CABG PLATO-defined major bleeding (3.9% vs 3.3%) and dyspnea (14% vs 8%); in PEGASUS, BRILINTA vs aspirin alone, TIMI Total Major bleeding (1.7% vs 0.8%) and dyspnea (14% vs 6%)

DRUG INTERACTIONS

• Avoid use with strong CYP3A inhibitors and strong CYP3A inducers. BRILINTA is metabolized by CYP3A4/5. Strong inhibitors substantially increase ticagrelor exposure and so increase the risk of adverse events. Strong inducers substantially reduce ticagrelor exposure and so decrease the efficacy of ticagrelor
• Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse events
• Monitor digoxin levels with initiation of, or change in, BRILINTA therapy

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

¹ Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior
myocardial infarction. N Engl J Med. 2015;372:1791-800

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 AstraZeneca’s largest outcomes trial with more than 21,000 patients from over 1,100 sites in 31 countries. The study assessed BRILINTA^® (ticagrelor) tablets at either 60mg twice daily or 90mg twice daily plus once daily 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. Only the 60mg dose is approved for use in patients with a history of MI beyond 12 months. The study was conducted in collaboration with the Thrombolysis in Myocardial Infarction (TIMI) Study Group from Brigham and Women’s Hospital (Boston, MA, USA).

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-us.com.

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

CONTACTS

Michele Meixell, +1 302 885 2677, michele.meixell@astrazeneca.com (US)
Ayesha Bharmal +44 20 7604 8034, ayesha.bharmal@astrazeneca.com (UK/Global)

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