New dangers seen with abandoned Pfizer heart drug

By Bill Berkrot and Ransdell Pierson

NEW ORLEANS/NEW YORK (Reuters) - Pfizer Inc.'s abandoned experimental heart drug, torcetrapib, failed to arrest clogging of arteries and was linked to a jump in blood pressure and serious cardiac events, even as it sharply raised "good" HDL cholesterol in a trio of clinical trials.

The results, described on Monday at the American College of Cardiology (ACC) scientific meeting in New Orleans, suggest the dangers of torcetrapib outweigh its ability to raise HDL levels by more than 60 percent over Lipitor alone.

The trials raised stronger doubts about the future of similar drugs being developed by other companies.

Pfizer in December ended the most expensive clinical drug development program in history after a different large study showed the drug raised the risk of death among heart patients.

The company had hoped that torcetrapib would reduce or at least halt progression of plaque within coronary arteries and within the main artery to the brain. The drug is designed to boost HDL, the "good" form of cholesterol that removes "bad" LDL cholesterol from the blood.

All the studies tested it in combination with Pfizer's widely used LDL-lowering drug Lipitor versus Lipitor alone.

Torcetrapib's overall performance widely missed the mark, said Steven Nissen, head of cardiology at the Cleveland Clinic who led the coronary artery study.

"Whether this failure represents a problem unique to torcetrapib or suggests a lack of efficacy for the entire class of similar drugs remains to be determined," Nissen said.

"Our findings demonstrate the great difficulty in developing therapies to interrupt the atherosclerosis process," he said.

NO BENEFICIAL EFFECTS

It had been widely speculated that a demonstration of the drug's ability to slow or halt progression of artery-clogging plaque might have been a potential indication of the viability of the entire class of the drugs called CETP inhibitors that are designed to raise HDL levels.

In all three studies presented Monday, however, torcetrapib showed no beneficial effects on plaque clogging the arteries as measured by intravascular ultrasound.

In two studies of the drug's effect on the carotid artery -- the main conduit of blood to the brain -- there was actually some worsening of the disease in the torcetrapib group, while the Lipitor-only group had some plaque regression.

There was also a near doubling of adverse cardiac events with torcetrapib in the carotid studies, and all three trials saw a jump in blood pressure with torcetrapib, often by significant amounts, researchers said.

High blood pressure is itself a major risk factor for heart attacks and strokes, although many doctors have expressed skepticism that the blood pressure increase seen in many torcetrapib trials could account for the unacceptably high death rate in the study that scuttled the program.