The American Heart Association meeting has been going on this week, and it's one of the high-profile venues for cardiovascular research results. Today, among other things, came the details of a head-to-head trial (called, in standard cute-acronym style, IDEAL) of Pfizer's Lipitor (atorvastatin) against Merck's soon-to-be-generic Zocor (simvastatin). Pfizer's worried about that change in status, since this will be the first of their major statin competition to go off patent - the fear is that HMOs will insist on a switch to the cheaper medicine as quickly as possible.
So an 8,800-patient trial was run, using patients who had already had one heart attack (although not necessarily a recent one). One group got high-dose Lipitor, and the other got the standard dose of Zocor, and they were followed for an average of nearly five years. This was one expensive trial. The hope was the the Lipitor regimen, which lowers LDL more, would show a beneficial effect. Which it did - and which it didn't.
Pfizer's problem is that they missed their biggest target, a reduction in "major coronary events". The Lipitor and Zocor groups were indistinguishable. In some secondary categories, though, Lipitor came out ahead, such as when you look only at the frequency of nonfatal heart attacks. But overall cardiovascular mortality was the same for both groups. So Pfizer can claim some benefit from Lipitor, but not in the categories that would immediately convince cardiologists. I'm sure they'll be giving it the good ol' Groton try, though
All this is quite interesting, since Lipitor had already vanquished another statin, Pravachol, in a study in recent heart-attack survivors. Merck, meanwhile, had also tested Zocor in angioplasty patients, with disappointing results as compared to Lipitor's effects in a similar patient population. You can bet that Pfizer expected more from this study, and I'm still a bit puzzled that they didn't get it.
Analysts have already cut their sales estimates for Lipitor next year, figuring - surely correctly - that these results will cause some shift toward generic simvastatin. That doesn't do Merck much direct good, but it leaves them with an opening for their combination therapy Vytorin, which is Zocor plus Schering-Plough's cholestrol absorption inhibitor Zetia. And as fate would have it, they're running a big comparison of Vytorin to Zocor right now, since the darn stuff is going off patent, anyway.
The earlier comparison trials had already poked a hole in the "lower LDL is always better" hypothesis, which has been one of Pfizer's arguments for Lipitor. (It's also the first place that Merck and Schering-Plough chose to attack them). Still, they always had good clinical data to point at, too, but now that advantage has been eroded. So in the last fifteen months, we've had the spectacle of Merck trying to shoot down Lipitor and winging its own drug, and then Pfizer aiming at Zocor and blowing a hole in Lipitor instead. What a business. Can anyone name me another where things like this are a way of life?