Biotech Values

[genisi]

Urche on xarelto ACS data

There is also a problem now with dosing. Faced with data that even this small dose of Xarelto is associated with 4 fold major bleeding risk, how are we going to view the higher doses (I think it was 20 mg) approved for other indications such as A. fib?

I think dosing will be a problem only in patients suffering from both AF and ACS.

The biggest problem I see is that even for the lower 2.5 mg BID dose, the "major bleeding risk" is about 4X that for placebo (2.1% vs 0.6%).

No, the 2.1% figure was for both doses. The 2.5mg dose had less bleeding (absolute rates were 1.8%) than the higher dose for the primary safety endpoint (TIMI major bleeding not related to coronary-artery bypass grafting). Also, like you wrote, there was not a significant increase in fatal bleeding (0.3% vs. 0.2%, p=0.66).

The bleeding risk would be tolerated, of course, if the efficacy were high enough. But, the absolute survival benefit of treatment with riva was only 9.1 vs 10.7 for placebo or 1.8%.

This was again for both doses, if you look at survival benefit with the 2.5mg dose, (which is the one I referred to in #msg-68962285 ) as compared with placebo, reduction in the risk of death from CV causes was 2.7% vs. 4.1% (HR=0.66; 95% CI, 0.51 to 0.86; P=0.002), that's a relative reduction of 34%! and the risk of death from any cause was 2.9% vs. 4.5% (HR=0.68; 95% CI, 0.53 to 0.87; P=0.002) that's a relative reduction of 32%. I don't think that

from a clinical viewpoint, that makes little difference

Given the significant reduction in death and the absolute major bleeding rates, I think the 2.5mg rivaroxaban dose has a good risk/reward profile in ACS.