I’ve already written about how Eli Lilly’s (NYSE:LLY) inhibitor of cholesteryl ester transfer protein (CETP) did not work in the clinic. Now that the data from their failed trial have been published in the NEJM, though, it’s worth taking a look at a few graphs (first pointed out to me on Twitter by Sek Kathiresan. Shown are the effects of evacetrapib on HDL and LDL, and he’s right: if you’d seen these graphs ten years ago, you’d have said that you’re looking at a cardiovascular wonder drug for sure. LDL down 30%, HDL up 125% – what else do you want?
Well, you want actual cardiovascular outcomes. And that’s where this graph comes in. 12,000 total patients for over two years, and this is what you get: nothing. You lose – good day, sir! Absolutely no change in CV events whatsoever. There is something that we don’t understand here, about the various effects of CETP inhibition, or the various types of HDL and LDL and their downstream effects, or about the influence of these two on cardiovascular health in general. CETP inhibitors have been a total wipeout for every single company that has tried to develop a drug in this area. Merck has not yet released data on their own compound in this area, anacetrapib, but let’s put it this way: if it works, it’ll be one of the major medical mysteries of our time.
And I think I’ll add this every time we have a big drug trial wipe out: keep in mind, that under a safety-only regulatory regime, that people would have been taking this drug (and paying for it, one way or another) for the last few years now, and it would have done them no good at all. When they could have been actually taking something that might help them. We do not know enough about investigational drugs to approve them without efficacy data.