It’s been a while since CETP came up on this site as a drug target. This has been many companies’ best shot at an HDL-raising therapy, to go along with the LDL-lowering effects of the statins (and now the PCSK9 inhibitors). The prospect of a two-front attack on cardiovascular disease (and the cardiovascular disease market) has led to a vast amount of time, effort, and investment over the years (late-stage trials in this area are almost always gigantic and costly). But looming over the whole CETP landscape is the dust cloud caused by the failure, back in 2006, of Pfizer’s torcetrapib, which was the most advanced drug in the class. That was a terrible shock, for sure – looking back, there were some warning signs in the earlier clinical data, but no one expected the drug to crater as badly as it did in Phase III.
In the years since, the companies pushing hardest to make a success out of a CETP inhibitor have included Merck and Lilly. (Roche gave up on their entry in 2012). And now Lilly is out this morning with news that their drug, evacetrapib, has failed in Phase III. In this case, it wasn’t toxicity, as with Pfizer’s compound, which showed a slightly higher death rate in the treatment group. But it was sheer lack of efficacy. The data monitoring committee decided that there was basically no chance that the compound would make its primary endpoints, the way things were going, and recommended a complete halt.
When torcetrapib failed, there were a number of rationales advanced for how that could have happened. The drug seemed to cause some electrolyte imbalances, and raised blood pressure a bit on its own, for example. Given the experiences since then, though, it would seem that these could account for the swing to actual harm, as opposed to just doing no good. But it’s also looking harder and harder to deny that inhibiting CETP is just that: an intervention that does nothing useful. Every single company so far that has ventured into this area has had cause to regret it. And there have been many, since many of them didn’t even make it to the clinic, which in retrospect makes them fortunate, I’d say.
All this makes a person wonder, very very much, about Merck’s anacetrapib. As far as I know, they’re officially pushing on with it, but that took nerve even after Pfizer’s failure. Now after Roche, and now after Lilly, what do they have? Either CETP inhibitors are a much more varied lot than you’d ever think, or they’re probably going down the same chute as everyone else. . .
Update: Lilly’s stock has been taking a beating this morning, an unusually large move for a company its size. And Merck’s stock is feeling the pressure as well, as the pessimism spreads.