BRILINTA Approved in the US to Reduce the Risk of a First Heart Attack or Stroke in High-Risk Patients with Coronary Artery Disease

WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca’s BRILINTA^® (ticagrelor) has been approved in the US to reduce the risk of a first heart attack or stroke in high-risk patients with coronary artery disease (CAD), the most common type of heart disease.

The approval by the US Food and Drug Administration (FDA) was based on positive results from the Phase III THEMIS trial. The trial showed a statistically significant reduction in the primary composite endpoint of major adverse cardiovascular (CV) events at 36 months with aspirin plus BRILINTA 60mg versus aspirin alone in patients with CAD and type 2 diabetes (T2D) at high-risk of a first heart attack or stroke. The primary composite endpoint was driven by a reduction in heart attack and stroke.

This is the first regulatory approval for aspirin plus BRILINTA dual antiplatelet therapy in patients who have a high CV risk, but without a history of heart attack or stroke.

Deepak L. Bhatt, MD, MPH, THEMIS trial Co-Chair, Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital, and Professor of Medicine at Harvard Medical School, Boston, US said: “Coronary artery disease is a potentially life-threatening condition that causes significant morbidity in many people. The addition of ticagrelor to aspirin offers a new therapeutic option to decrease the likelihood of both heart attack and stroke, a significant advance in our ability to treat these high-risk patients.”

Gabriel Steg, MD, THEMIS trial Co-Chair and Professor at Université de Paris, said: “THEMIS for ticagrelor was a large, multi-national trial of more than 19,000 patients with coronary artery disease and type 2 diabetes. Around one third of patients with coronary artery disease have type 2 diabetes, putting them at higher risk of heart attack or stroke, than patients without diabetes. Today’s approval brings new hope to patients at risk of experiencing a first heart attack or stroke.”

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, said: “Today’s approval of BRILINTA is important news for patients with coronary artery disease who will now have a new therapy option to reduce the risk of a first heart attack or stroke. This new indication is a further testament to the overwhelming science supporting BRILINTA in the management of patients with coronary artery disease at high risk for cardiovascular events.”

The THEMIS trial demonstrated the relative risk reduction of the composite endpoint of heart attack, stroke and CV death by 10% (absolute risk reduction; 0.8%, 7.7% vs 8.5%) with aspirin plus long-term BRILINTA compared to aspirin alone in patients who had CAD and T2D without a history of heart attack or stroke. While this indication is not limited to this setting, the efficacy of BRILINTA was established in a population with T2D in the THEMIS trial. The safety profile for BRILINTA was consistent with the known profile of the medicine with an increased risk of bleeding events observed.

The data from the THEMIS trial and the THEMIS-PCI sub-analysis were published in The New England Journal of Medicine and The Lancet respectively.

Regulatory submissions to expand the approved indication for BRILINTA based on the THEMIS trial are also under regulatory review in the EU, Japan and China.

AstraZeneca also recently announced the high-level results from the Phase III THALES trial that showed aspirin plus BRILINTA 90mg reduced the risk of the composite of stroke and death at 30 days after an acute ischemic stroke or transient ischemic attack, compared to aspirin alone.

BRILINTA is not indicated in patients with minor acute ischemic stroke or high-risk transient ischemic attack.

BRILINTA is approved in more than 110 countries for the prevention of atherothrombotic events in adult patients with acute coronary syndrome (ACS), and in more than 70 countries for the secondary prevention of CV events among high-risk patients who have experienced a prior myocardial infarction.

INDICATIONS

BRILINTA is indicated to reduce the risk 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 risk of stent thrombosis in patients who have been stented for treatment of ACS.

BRILINTA is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events. While use is not limited to this setting, the efficacy of ticagrelor was established in a population with type 2 diabetes.

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.

In patients with CAD but no prior stroke or MI, 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

WARNINGS:

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 more frequently with BRILINTA than in patients treated with control agents. Dyspnea 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
• Ticagrelor can cause ventricular pauses. Bradyarrhythmias including AV block have been reported in the post-marketing setting. Clinical trials excluded patients at increased risk of bradyarrhythmias not protected by a pacemaker, and they may be at increased risk of developing bradyarrhythmias
• 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
• In patients with Heparin Induced Thrombocytopenia (HIT): False negative results for HIT-related platelet functional tests, including the heparin-induced platelet aggregation (HIPA) assay, have been reported with BRILINTA. BRILINTA is not expected to impact PF4 antibody testing for HIT

ADVERSE REACTIONS

• The most common adverse reactions (>5%) associated with the use of BRILINTA included bleeding and dyspnea

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
• As with other oral P2Y₁₂ inhibitors, co-administration of opioid agonists delay and reduce the absorption of ticagrelor. Consider use of a parenteral anti-platelet in ACS patients requiring co-administration
• 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

SPECIAL POPULATIONS

• Lactation: Breastfeeding not recommended

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

CAD and T2D

CAD is the most common type of heart disease. Ischemic heart disease is the leading cause of healthy life years lost due to disability in men and the second cause in women worldwide. The disease burden of atherosclerosis is significantly higher in patients with CAD and T2D than in CAD patients without T2D.

THEMIS

THEMIS is an AstraZeneca-sponsored, multi-national, randomized, double-blinded Phase III trial in patients with CAD and T2D with no prior heart attack or stroke. More than 19,000 patients were randomized across 42 countries in Europe, Asia, Africa, North and South America. THEMIS was designed to test the hypothesis that aspirin daily plus BRILINTA 60mg twice daily would reduce MACE (major adverse cardiac events), compared with aspirin alone. CAD was defined as a history of percutaneous coronary intervention (PCI), coronary artery bypass surgery, or at least a 50% narrowing of a coronary artery. Additionally, THEMIS-PCI is a clinically meaningful and prespecified sub-analysis of patients (11,154 which is 58% of total patients) who had previously undergone percutaneous coronary intervention (PCI).

BRILINTA

BRILINTA (ticagrelor) is an oral, reversibly binding, direct-acting P2Y12 receptor antagonist that works by inhibiting platelet activation. BRILINTA, together with aspirin, has been shown to significantly reduce the risk of major adverse cardiovascular events (myocardial infarction [MI], stroke or CV death) in patients with acute coronary syndrome (ACS) or a history of MI.

AstraZeneca in CV, Renal & Metabolism (CVMD)

CV, renal and metabolism together form one of AstraZeneca’s main therapy areas and a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVMD diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism and Respiratory. 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 and follow us on Twitter @AstraZenecaUS.

Disclosure

Brigham and Women’s Hospital received research funding for Dr Bhatt’s role as co-Chair of THEMIS and THEMIS-PCI.

US-40170 Last Updated 6/20