FDA Approves AstraZeneca's Brilinta for Treating ACS

July 20, 2011—AstraZeneca Pharmaceuticals LP (Wilmington, DE) announced that the US Food and Drug Administration (FDA) has approved Brilinta (ticagrelor) tablets, an oral antiplatelet treatment to reduce the rate of myocardial infarction (MI) and cardiovascular death in adult patients with acute coronary syndrome (ACS; unstable angina non–ST-elevation MI or ST-elevation MI).

AstraZeneca stated that ticagrelor is a direct-acting P2Y12 receptor antagonist in a chemical class called cyclo-pentyl-triazolo-pyrimidines. It is a reversibly binding oral adenosine diphosphate receptor antagonist. Ticagrelor has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, or stroke compared to clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, New York, NY). The difference between treatments was driven by cardiovascular death and MI, with no difference in stroke.

In patients who were treated with percutaneous coronary intervention, Brilinta was shown to reduce the rate of stent thrombosis. Brilinta has been studied in ACS patients in combination with aspirin. Maintenance doses of aspirin > 100 mg daily were shown to decrease the effectiveness of Brilinta and should be avoided, the company advised.

With approval in the United States, AstraZeneca stated that it will begin the process of working with insurance and government entities to negotiate reimbursement terms before Brilinta is commercially available. Brilinta will be 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. After an initial loading dose of aspirin, Brilinta should be used with a maintenance dose of 75- to 100-mg aspirin once daily; for most patients, an 81-mg aspirin dose is likely to be used, the company advised.

According to AstraZeneca, the FDA approval is based on data from PLATO (A Study of Platelet Inhibition and Patient Outcomes), a superiority trial that compared treatment with Brilinta to clopidogrel in 18,624 ACS patients worldwide.

The company advised that, like other antiplatelet agents, Brilinta can cause significant, sometimes fatal, bleeding. In PLATO, there was no statistical difference in patients who were treated with Brilinta compared to patients who were treated with clopidogrel in total major bleeding events (11.6% vs 11.2%), including fatal and fatal/life-threatening bleeding events. Non–coronary artery bypass graft major and minor bleeding events (8.7% vs 7%) were more common with Brilinta versus clopidogrel. The most commonly observed adverse reactions associated with the use of Brilinta versus clopidogrel were bleeding (11.6% vs 11.2%) and dyspnea (14% vs 8%).

“In clinical trials, Brilinta was more effective than Plavix in preventing heart attacks and death, but that advantage was seen with aspirin maintenance doses of 75 to 100 mg once daily,” commented Norman Stockbridge, MD, PhD, Director of the Division of Cardiovascular and Renal Products in the FDA's Center for Drug Evaluation and Research.

The FDA stated that Brilinta was approved with a Risk Evaluation and Mitigation Strategy, a plan to help ensure that the drug's benefits outweigh its risks. As part of that plan, the company must conduct educational outreach to physicians to alert them about the risk of using high doses of aspirin. In addition, Brilinta will be dispensed with a Medication Guide that informs patients of the most important information about the medication. The guide will be distributed each time a patient fills their prescription, noted the FDA.