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November 19, 2010
Merck's CETP Compound: Still Alive, But The Big Fun Awaits
Four years after the torcetrapib disaster, Merck has released some new clinical trial data on their 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 compound had already proven the CETP mechanism; their 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 at the interim - that, we'll see.
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, and good luck to everyone involved. . .
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