Merck's anacetrapib has curiously strong effect on lipids

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Researchers said a new kind of cholesterol-modifying drug from Merck demonstrated remarkably strong LDL-lowering and HDL-raising effects, and appeared safe from a cardiovascular standpoint, stoking doctors' optimism that it could reach market.

The drug, anacetrapib, significantly raises good cholesterol while reducing bad cholesterol by almost half, according to results read yesterday at the AHA meeting in Chicago. Anacetrapib did not appear to have the blood pressure-raising effects of torcetrapib, another agent in the same class that was linked to increased deaths and was scrapped by Pfizer after the firm spent almost a billion dollars on development.

An AHA press release on the Define trial quoted lead investigator Dr. Chris Cannon, who characterized anacetrapib's lipid effects in the trial as having “a knock-your-socks-off effect on HDL and a jaw-dropping effect on LDL.”

The research, by Cannon and colleagues at Brigham and Women's Hospital in Boston, revived hopes that the class of atherosclerosis drugs known as cholesterylester transfer protein (CETP) inhibitors could one day hit pharmacy shelves.

Following Pfizer's 2006 discontinuation of torcetrapib, physicians had speculated that the same problem that doomed that drug might plague the entire class. In 2007 that fear was eased somewhat, when data showed it was actually due to the Pfizer compound's particular tendency to raise levels of adrenal hormones known to boost fatty plaque and blood pressure. Merck had said at the time that anacetrapib does not have the same effect on the adrenal gland but had halted study.

While the Define results are encouraging, safety concerns have not been completely put to rest, and results must be borne out by larger trials. At a press conference yesterday, Merck and Oxford University said they would start a 30,000-patient study of anacetrapib among patients with heart disease who are on statin therapy, in order to test the drug's clinical effect over four years. This mega trial, known as Reveal, will help confirm whether anacetrapib's HDL-boosting effect actually prevents coronary deaths and heart attacks. It's slated to start next year.

The history of this drug class is littered with discontinued R&D projects. The only other company as far along is Roche, whose dalcetrapib is in Phase III testing. The need to show real-world clinical benefit, not just a change in a risk factor, assures that both drugs still remain several years away from launch.

The Define data came a day after positive results from another trial generated excitement about Johnson & Johnson/Bayer's Phase III blood thinner, Xarelto. Based on that trial, Rocket AF, analysts said Xarelto is likely to join Boehringer Ingelheim's Pradaxa as a viable alternative to warfarin.

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