Doctors Divided Over Loss of Experimental Cholesterol Drug

Pfizer compound sought to raise 'good' cholesterol, but trial revealed unacceptable death rate

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By Amanda Gardner
HealthDay Reporter

MONDAY, Dec. 4, 2006 (HealthDay News) -- While some heart experts are calling Pfizer Inc.'s decision to halt development of a promising new cholesterol drug a major disappointment, other experts note that existing medicines offer significant benefits.

Pfizer announced on Saturday that an independent board monitoring the developmental drug torcetrapib had recommended the clinical trial be stopped due to a disproportionately large number of deaths and cardiovascular problems among patients receiving the drug. Unlike traditional cholesterol drugs, called statins, that work by lowering levels of LDL (bad) cholesterol, torcetrapib was designed to raise levels of good (HDL) cholesterol.

"It's big news," said Dr. Daniel Fisher, clinical assistant professor of medicine at New York University School of Medicine. "This was going to be a blockbuster drug because it represented a new form of treatment -- raising HDL cholesterol significantly. It had a lot of promise to it. Heart disease is the number one killer," Fisher explained.

But not all clinicians agree that the loss of the drug is a devastating blow in the fight against heart disease.

"It's a significant disappointment, but it's not setting the field back," said Dr. Robert Myerburg, professor of medicine and physiology at the University of Miami Miller School of Medicine. "What we have that's good is good. It was anticipated that this would be another significant benefit, and it's not working out. But the notion of doom and gloom doesn't make any sense."

Dr. Raymond Gibbons, president of the American Heart Association and co-director of the Nuclear Cardiology Lab at the Mayo Clinic in Rochester, Minn., added: "Whenever we hear that a potential new drug for the treatment of heart disease is not going to come to market, it's disappointing. However, that's the reason we do clinical trials and careful studies of these compounds before they're released for general use."

Pfizer said it has asked that all clinical investigators conducting trials warn patients to stop taking the drug immediately.

According to Pfizer spokesman Paul Fitzhenry, in a trial of 15,000 patients, 82 of those taking the combination of torcetrapib and the statin Lipitor had died, compared to 51 deaths among those taking Lipitor alone. Pfizer said the study did not raise any questions about Lipitor's safety.

There had been concerns about torcetrapib, which was designed to be taken with a statin like Lipitor, because a recent study showed it triggered a slight increase in blood pressure.

But only last week, Pfizer had announced its intention to file an application with the U.S. Food and Drug Administration for approval of torcetrapib by the second half of next year. The company had expected to sell torcetrapib in combination with Lipitor, which is the company's -- and the world's -- best-selling drug.

LDL cholesterol is worrisome because if too much circulates in the blood, it can help to form plaque -- a thick, hard deposit that can clog arteries. This can lead to the creation of clots that can cause heart attacks or strokes. HDL cholesterol is beneficial because it carries cholesterol away from arteries and back to the liver, where it's passed from the body, according to the American Heart Association.

One remaining question is whether the finding on torcetrapib represents a so-called "class effect," because there are other, similar drugs currently in various stages of development.

"We have no idea if this effect will extend to other drugs in the class," Gibbons said. "We've learned from experience that it's incorrect to extrapolate the findings from one drug to another. This drug is in a different class than any of the drugs currently used by patients, so patients currently taking cholesterol-lowering drugs should not be concerned by the findings of this study. They should not decide they should not take existing therapies."

Myerburg added, "I don't think there's any sense at this point of whether this is a class effect."

Heart patients still have other options, however, namely the cholesterol-lowering statins.

And, with the Pfizer study cut short, it's also unclear if torcetrapib would have turned out to be a blockbuster along the lines of Lipitor.

"There was no reason to think that there would be this kind of harm, but the other side of the coin is how much added benefit would this strategy have given to what we already have," Myerburg said. "There could have been a surprise there. We could have been wrong on the upside as well."

Perhaps the only good news for Pfizer is that the negative study results came out in pre-marketing studies, thus avoiding the litigation problems Merck & Co. is now facing with its derailed arthritis drug Vioxx.

The torcetrapib study was large enough to detect a relatively small number of problems. Usually such issues only surface when a drug is approved and marketed.

"Most studies aren't that big," Myerburg said. "This is a statement about the importance of doing adequately sized trials and of doing post-marketing studies. Cut this study in half, and you might have seen a benefit but missed the adverse effects."

More information

For more on cholesterol and heart disease, visit the American Heart Association.

SOURCES: Raymond Gibbons, M.D., president, American Heart Association, and professor of medicine, and co-director, Nuclear Cardiology Lab, Mayo Clinic, Rochester, Minn.; Daniel Fisher, M.D., clinical assistant professor of medicine, New York University School of Medicine, New York City; Robert J. Myerburg, M.D., professor of medicine and physiology, University of Miami School of Medicine; U.S. Food and Drug Administration statement, Dec. 4, 2006

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