Wednesday, 29 April 2015
AstraZeneca (NYSE: AZN) today announced that the US Food and Drug Administration (FDA) has accepted a supplemental new drug application (sNDA) and granted Priority Review for BRILINTA® (ticagrelor) tablets for patients with a history of heart attack. The sNDA is based on the results of the PEGASUS-TIMI 54 study, a large-scale outcomes trial in more than 21,000 patients that investigated 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 enrollment. The Prescription Drug User Fee Act goal date will be in the third quarter of 2015.
Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca, said: "Recent research has shown that one in five patients will have a further heart attack, stroke or cardiovascular death in the subsequent three years following a heart attack, even if they are event free after the first 12 months. There is a clear need for treatment options beyond the current standard of care of aspirin for the long-term prevention of atherothromobotic cardiovascular events in patients with a history of myocardial infarction. Today’s milestone reinforces the importance of investigating clinical questions that address unmet patient need and we look forward to working with the FDA as they review our submission.”
A Priority Review designation is granted to medicines that the FDA determines have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.
The PEGASUS TIMI-54 study was presented during the opening late-breaking clinical trial session of the American College of Cardiology’s 64th Annual Scientific Session and Expo on March 14, 2015, and was also simultaneously published in theNew England Journal of Medicine online.
PEGASUS-TIMI 54 is part of AstraZeneca’s PARTHENON program. The PLATO study, involving over 18,000 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 assessing ticagrelor for the prevention of cardiovascular events in patients with peripheral arterial disease, ischemic stroke or transient ischemic 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.
BRILINTA 90-mg tablets 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) 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 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
- 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
- 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
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&MeTM Prescription Savings Program. To determine eligibility, patients can visit www.AZandMe.com or call 1-800-AZandMe (292-6363).
NOTES TO EDITORS
1TIMI Major Bleeding Classification
- Any intracranial bleeding, or
- Clinically overt signs of hemorrhage 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).
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 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. 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. 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® (ticagrelor) tablets
BRILINTA is an oral antiplatelet treatment for ACS. BRILINTA is a direct-acting P2Y12 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 cardiovascular (CV) events, such as a heart attack or CV death, in patients with acute coronary syndrome (ACS). BRILINTA is available in 90-mg tablets to be administered with a single 180-mg oral loading dose (two 90-mg tablets) followed by a twice daily, 90-mg maintenance dose. Following an initial loading dose of aspirin, BRILINTA should be used with a maintenance dose of 75 mg - 100 mg aspirin once daily, 81-mg aspirin dose in the US.
BRILINTA is a registered trademark of the AstraZeneca group of companies.
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-us.com.
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