New blood thinner ticagrelor to undergo FDA's panel review
The FDA advisory committee will vote tomorrow on AstraZeneca' blood-thinner Brilinta that works to reduce the rate of thrombotic events in patients with acute coronary syndromes.
According an international study by AstraZeneca, antiplatelet ticagrelor (Brilinta) appeared more effective than clopidogrel (Plavix) in patients with acute coronary syndrome.
Although the FDA reviewers are concerned that the findings did not hold up in a U.S. population, their view is generally positive. According to a statement released by the agency, the consensus view was that the therapy is approvable provided the agency requires a post-approval efficacy study in Americans once it’s marketed.
Similar to two other drugs clopidogrel (Plavix) and prasugrel (Effient) that are already approved, ticagrelor is designed to prevent platelets in the blood from clumping together to form clots, which can cause heart attacks and strokes.
In the year-long study called PLATO (Platelet Inhibition and Patient Outcomes), 18,624 ACS patients were given either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 to 600 mg loading dose, 75 mg thereafter).
The results showed that ticagrelor was associated with fewer strokes, heart attacks, and cardiovascular deaths than clopidogrel (Plavix) with 9.3% of patients with ticagrelor reaching the composite endpoint of cardiovascular death, stroke, or myocardial infarction versus 10.9% of those randomized to clopidogrel.
However, according to a review of the data by FDA staff led Thomas Marciniak, MD, who works in the FDA's Department of Cardiovascular and Renal Products, However, subgroup analysis found that ticagrelor had no benefit for the study's 1,814 U.S. participants, and American patients taking ticagrelor actually had a 27% greater risk of having a clinical event than those taking clopidogrel.
Researchers for the company explained that the discrepancy could be due to a higher level of aspirin dosing in the U.S. Ticagrelor's label states that it should be administered with low dose (75 to 100 mg) of aspirin.
Marciniak rejected that explanation, writing "... aspirin dosing does not explain the disparate results. " FDA reviewers called the U.S. discrepancy "the big issue" in AstraZeneca's application.
Safety for ticagrelor was another issue raised by Marciniak. Ticagrelor caused an increase in bleeding. Some 14.5% of patients in the ticagrelor group experienced bleeding compared to 13.2% in the clopidogrel group.
The FDA's Cardiovascular and Renal Drugs Advisory Committee will vote tomorrow on whether to recommend Brilinta for approval which is to be decided by September 19.