TICAGELOR ; FDA WAITS. NEED MORE ANALYSIS

Ticagrelor is a new anti-platelet agent ( like clopidogrel ) in treatment of atherothrombosis. It is manufactured and marketed by Astra Zaneca. Last July, I wrote i this blog that the FDA advisory Panel for CVS and Renal drugs had met and voted 7:1 to recommend approval for ticagrelor to be used in the treatment of acute coronary syndrome. They based their recommendation largely in the outcomes of the study " Platelet inhibition and Patient Outcomes" trial. This is a very large controlled trial of 18,000 patients, half on ticagrelor + aspirin, and the other half on clopidogrel and aspirin. They compared the outcomes after 12 months. The primary composite endpoint was CV deaths, AMI and strokes. This showed a benefit for ticagrelor + aspirin over clopidogrel + aspirin. The P value was < 0.001.
Having read that, I flt that with the recommendation by the advisory committee, that the drug would be approved. So the headlines in July 2010.
But this was not to be. Last week, the European Drug Authority approved it for use in Europe, but the US FDA met and decided to withhold approval, and asked for more detailed analysis. Now this is a bit strange as AstraZ was waiting to time their launching.
So cyberspace is flying with all kinds of arguments for and against approval. The communications by the "big boys" is quite interesting, to see how the system works.
Apparently, the small prints are important here. What I did not know in July was that there seemed to be a difference in outcome in the US, Canada, Russia centers. Remember, this was a multi-center trial across 43 countries. Apparently, most centers that were monitored by AstraZ, returned positive results ( Ticagrelor was more efficacious than Clopidogrel ). Some centers were monitored by independent observers. These included US, Canada, Russia, Denmark, Australia, Taiwan, Norway. With US, Canada, Russia, ticagrelor was less efficacious than Clopidogrel. In the rest monitored by independents, the results were neutral. About 20% of patients were contributed by Poland and Turkey, and monitored by AstraZ. The results here were positive for Ticagrelor. Interesting. No wonder FDA wants a re-look at the data and analysis.
Reading between the lines, it also seem that the FDA may not be very pleased that the US, Canada data, is over-ridden by the Polish, Turks data. That positive results from Poland and Turkey, may influence treatment practice in US, when the US data is at odds. Interesting.
Lets see what the new analysis will end up with. Keep a watch out on this page, all those interested. I am sure there will be more coming.

WISHING ALL READERS, A VERY MERRY XMAS AND A VERY HAPPY, HEALTHY AND PROSPEROUS NEW YEAR 2011.