Merck's CETP Compound Sails Ahead Into Potentially Murky Waters

Includes: MRK, PFE
by: Derek Lowe

Four years after the torcetrapib disaster, Merck (NYSE:MRK) has released some new clinical trial data on its own CETP inhibitor, anacetrapib. It's doing what it's supposed to, when added to a statin regimen: Decrease LDL even more, and strongly raise HDL.

So that's good news ... but it would actually be quite surprising if these numbers hadn't come out that way. Pfizer's (NYSE:PFE) compound had already proven the CETP mechanism; its compound did the same thing at this stage of the game. The problems came later -- and how. And that's where the worrying kicks in.

As far as I know, no one is still quite sure why torcetrapib actually raised the death rate slightly in its Phase III treatment group. One possible mechanism was elevated blood pressure (part of a general off-target effect on the adrenals) and Merck saw no sign of that. But no matter what, we're going to have to wait for a big Phase III trial, measuring real-world cardiovascular outcomes, to know if this drug is going to fly -- and we're not going to see that until 2015 at the earliest. Well, unless there's unexpected bad news in the interim.

I hope it doesn't happen. If the whole LDL-bad / HDL-good hypothesis is correct, you'd think that a CETP inhibitor would show a strong beneficial effect. This compound is either going to help a lot of people, or it's going to tell us something really significant that we didn't know about human lipid handling (and/or CETP). Problem is, telling us something new is almost certainly going to be the same as telling us something bad. It's still going to be a long road in this area; good luck to everyone involved.