FDA Advisory Committee Recommends Approval of Ticagrelor for ACS

July 29, 2010—AstraZeneca (Wilmington, DE) announced that the US Food and Drug Administration's (FDA) Cardiovascular and Renal Drugs Advisory Committee recommended that the FDA approve AstraZeneca's investigational drug ticagrelor for the reduction of thrombotic events in patients with acute coronary syndromes (ACS).

Ticagrelor is an investigational oral antiplatelet treatment for ACS. 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, the company stated.

The advisory committee voted 7 to 1 for ticagrelor to be approved for reducing thrombotic events in patients with non-ST-elevation (NSTEMI) and ST-elevation (STEMI) ACS intended to be managed by percutaneous coronary intervention. The committee also voted 7 to 1 for ticagrelor to be approved for reducing thrombotic events in patients with NSTEMI and STEMI ACS intended to be managed medically.

According to AstraZeneca, the review by the advisory committee is based on the results of PLATO (A Study of Platelet Inhibition and Patient Outcomes). PLATO was a large (18,624 patients in 43 countries) head-to-head patient outcomes study of ticagrelor versus clopidogrel designed to establish whether ticagrelor could achieve clinically meaningful cardiovascular and safety endpoints in ACS patients above and beyond those afforded by clopidogrel.

PLATO was designed to reflect current clinical management of ACS patients and included and represented all types of ACS patients (STEMI, NSTEMI, and unstable angina) whether they underwent invasive procedures or were medically managed. As presented to the FDA advisory committee, ticagrelor showed a reduction of cardiovascular events (death, myocardial infarction, stroke) over clopidogrel (9.8% vs 11.7% at 12 months; 16% relative risk reduction; 95% confidence interval, 0.77–0.92; P < .001) without an increase in overall major bleeding (11.6% vs 11.2%, P = .43). Across the overall PLATO population, there was an 11% risk of major and minor bleeding.

The company stated that it would continue discussions with the FDA as it evaluates the panel's recommendation and completes its review of the new drug application. AstraZeneca filed the regulatory submission for ticagrelor in the second half of 2009. The proposed trade name for ticagrelor in the United States is Brilinta. Ticagrelor is also currently under regulatory review in nine territories around the world, including the European Union, Canada, and Brazil. AstraZeneca noted that although the FDA is not required to follow this guidance, the agency takes the advice into consideration when rendering its final decisions on pending applications and other public health matters.