The novel antiplatelet drug ticagrelor (Brilinta) has failed to win FDA approval, at least for now, its manufacturer said.
AstraZeneca announced late Thursday that it had received a complete response letter from the FDA, requesting additional analyses of data from the product's pivotal clinical trial, called PLATO.
But the agency did not indicate that entirely new trials would have to be conducted, AstraZeneca said in a statement.
"The company remains confident in the NDA [new drug application] submission for ticagrelor and in its ability to respond to the agency's questions," according to the statement.
The denial was unexpected, given the favorable review in July by the FDA's advisory committee on cardiovascular drugs.
The panel voted 7-1 to recommend approval for reducing thrombotic events in patients with acute coronary syndrome (ACS) conditions including unstable angina, non-ST segment elevation myocardial infarction (NSTEMI), and ST segment elevation myocardial infarction (STEMI) who are going to be treated with PCI.
By the same margin, the panel also backed ticagrelor for ACS patients slated for medical therapy instead of PCI.
Key to the committee vote and the ultimate approval was the PLATO trial, reported in 2009, pitting ticagrelor head-to-head against clopidogrel (Plavix) in more than 18,000 patients.
The international trial found a lower risk of major cardiovascular events in patients taking ticagrelor. Some 9.8% of ticagrelor patients had one or more of these events (cardiovascular death, stroke, or myocardial infarction) versus 11.7% of those taking clopidogrel.
But there had been questions about how to interpret this result, since no benefit was seen among the 1,400 U.S. patients included in PLATO.
In fact, U.S. participants taking ticagrelor were 27% more likely to suffer one of the endpoint events, though the difference fell short of statistical significance (hazard ratio 1.27, 95% CI 0.92 to 1.75).
Bleeding events were also more common with ticagrelor across the entire PLATO sample. Some 14.5% of patients in the ticagrelor group experienced bleeding, compared with 13.2% in the clopidogrel group (P=0.0083). However, life-threatening and fatal bleeds were not significantly increased in the ticagrelor group.
But FDA staff told members of the advisory committee that most major bleeds occurred in patients undergoing CABG procedures. Stopping the drug at least five days before such surgery would largely eliminate the risk, they said.
AstraZeneca's statement did not indicate what specific issues the FDA wanted it to address in the new PLATO analyses.
The agency was originally supposed to render a decision on ticagrelor by Sept. 16, but delayed its ruling for three months.