Derek Lowe has additional commentary on the muraglitazar data. Derek nails it:
The problem here is that muraglitazar (and all the PPAR alpha-gamma compounds that have gone into development) was supposed to be better for cardiovascular outcomes than the plain PPAR-gamma compounds that are already out there. Needless to say, it was also supposed to be better than a damned placebo, which it isn't. The entire dual-PPAR-agonist idea is in trouble. The whole point of adding PPAR-alpha activity was to improve blood lipid profiles, and pretty much the whole point of doing that is to improve cardiovascular health. The first part is working, but the second part, the important part, just doesn't seem to be happening. Looking at the data, I find it hard to imagine why anyone would take muraglitazar over the exisiting therapies, when there's no evidence for what is supposed to be its main advantage.
Derek is exactly right. The "addition" of alpha activity was supposed to result in improved cardiovascular outcomes, but this compound appears to have the opposite effect. It just goes to show you how little we sometimes understand about the effects of blocking such a ubiquitous receptor system like PPAR.
This candidate may be "approvable", but who is going to use it?
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