Merck Vioxx News and Press Releases - News Menu

Pharma Prophet

Matthew Herper, 02.07.05

Garret FitzGerald saw the Cox-2 debacle coming. Now he sees the drugs' salvation.

The news that blockbuster arthritis drugs Vioxx and Celebrex may cause heart attacks shocked consumers and decimated the shares of their respective makers, Merck and Pfizer. If only people had listened six years ago to pharmacologist Garret FitzGerald. When he began presenting work that warned of the problems with these drugs, nobody paid much attention.

They do now. FitzGerald, whose soft Irish brogue has become a contrarian voice in pharma, now contends that while these so-called Cox-2-inhibitor drugs are dangerous to some, they should remain on the market. (Merck's Vioxx was pulled in September.) If we learn more about them, he says, we'll get safer pain pills in the future and better treatments for heart disease and osteoporosis.

A handful of drug companies, including Merck, Ono Pharmaceutical and France's Servier, are now working with FitzGerald, the chairman of pharmacology at the University of Pennsylvania, to unearth successors to the now-disgraced Cox-2 class of painkillers.

What ruined the Cox-2s, says FitzGerald, is their lack of specificity. Cox-2 inhibitors, developed with much hype in the mid-1990s, block an enzyme called cyclooxygenase-2, in so doing shutting off a wide-reaching cascade of biochemical signals that take the form of fats called prostaglandins. But the body needs those prostaglandins. One, called prostacyclin, protects the heart.

If drug developers could better target their inhibitors farther down the prostaglandin chain, they might produce powerful drugs that could fight pain and avoid unknown, possibly fatal, side effects. Says FitzGerald, "This sorry episode has really highlighted how unfixed the development process is."

One possible inflammation target is a fat called prostaglandin E2. Another possible drug target is the prostaglandin thromboxane. Block it and you may reduce clotting around heart-threatening cholesterol plaques. Meanwhile, some signaling fats from the same family work like hormones to build bone mass, a key to treating osteoporosis. This research could also lead to urine and blood tests that would measure prostaglandin levels and predict those who would benefit from drugs like Celebrex and those for whom the drugs might cause heart attacks.

"We have to find a way to use these drugs chronically in people at low cardiovascular risk but high risk of stomach problems. They're going to be a nice case of individualized medicine," FitzGerald says.

FitzGerald, who is one of the world's best guides to the intricacies of prostaglandins, began calling for more scrutiny of Celebrex and Vioxx after doing studies on them in humans that were funded by the drugmakers themselves. In 1999 he published results in the Proceedings of the National Academy of Sciences that pointed out how blocking the enzyme Cox-2 prevented the production of prostacyclin. The likely result, he warned, would be heart attacks. He published 16 more papers on the subject over the next several years, advancing the topic.

"Right from the get-go," FitzGerald says, "we were able to propose that this wasn't something funny about one drug. It was a property that was likely to be shared by both."

Merck and Pfizer refused to fund his further research and continued pushing Cox-2s on tens of millions of people. Merck is belatedly back in his camp now. If the drugmakers are lucky, FitzGerald's research could help lead to a new generation of tailored cures.

Other Resources
Drug Stores
Medical Classifieds
Legal Search Engine
Top Mesothelioma Sites
Phone Cards

Vioxx-Search-Engine.com
7141 Oak Pointe Curve
Minneapolis, MN 55438 USA

©Copyright
Nielsen Technical Services
All Rights Reserved Worldwide