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 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.
GAPING HOLE
Pfizer spent an estimated $800 million on late-stage testing of torcetrapib with the hope that it would eventually replace its $13 billion-a-year cash cow, Lipitor, a member of the statin class of drugs that is expected to go off patent as soon as 2010.
The company had been planning to pair torcetrapib with Lipitor for a potent cholesterol therapy.
Torcetrapib's sensational failure blew a gaping hole in Pfizer's developmental pipeline and left investors and other drugmakers to wonder whether the entire class should be abandoned or the deadly effects seen in the earlier study were specific to torcetrapib.
Roche Holding AG and partner Japan Tobacco Inc. , as well as Merck & Co., are close to having to decide whether to push forward into expensive final-stage clinical testing of their own CETP inhibitors.
"Many people are trying to figure out how do we progress to the next stage -- or is this the end -- and it's really not clear, but it's not very encouraging at this point," said Dr. Christopher Cannon, a prominent cardiologist from Brigham and Women's Hospital in Boston.
Nissen, the outgoing ACC president, said that clinical work on other CETP inhibitors should continue.
"At this point obviously the drug is dead, but my view is we can't slam the door on the class," he said.
