Merck Says New Pain Reliever Gentler

NEW YORK – The data Merck & Co. released on its new pain reliever Arcoxia on Tuesday was good – but not sufficient to warrant an approval by the Food and Drug Administration later this month, doctors and analysts predicted.

That’s because Arcoxia is tainted by its successor drug Vioxx, which Merck pulled from the market last month after a study showed patients taking it had double the rate of heart attacks and strokes than those taking placebo.

“I don’t think I’d feel comfortable prescribing Arcoxia at this time. I want more due diligence on cardiac issues,” said Dr. Eric Matteson, a professor of medicine and consultant to the rheumatology department at the Mayo Clinic in Rochester, Minn.

A 7,111 patient study found that Arcoxia was gentler on the stomach than an older pain reliever, diclofenac, and didn’t increase the risk of adverse cardiovascular events. Data combined from numerous studies which included 6,700 patients also found patients taking Arcoxia didn’t have more heart attacks and strokes than those taking other pain relievers.

Still, most expect the FDA to wait to approve the drug until 2006 when Merck completes a 23,500 person study where assessing cardiovascular safety was the main goal. The other studies were designed to see if the drug was effective and gentler on the stomach than other treatments. These days cardiovascular safety outweighs gastrointestinal qualities.

“I’d be surprised if it were approved,” said Matteson. “I don’t feel a real need for another drug of this type.”

Vioxx and Arcoxia are joined by Pfizer Inc.’s Celebrex and Bextra in a class of drugs known as cox-2 inhibitors. The Vioxx debacle has put all the drugs under a microscope as many doctors fear they all may increase the risk of heart attack and strokes.

The signals from Pfizer are mixed: Last week Pfizer announced Bextra increased the risk of heart attacks in patients who had coronary bypass operations but on Monday said it planned a major study to see if Celebrex can help osteoarthritis patients at risk for cardiovascular disease.

Acting FDA deputy commissioner Dr. Janet Woodcock said on Monday that any new cox-2 inhibitor would be put “under careful scrutiny” before approval. The agency is slated to rule on Arcoxia by Oct. 30 and neither Merck or the agency would comment on the application.

Woodcock also said the FDA would hold an advisory committee meeting early next year to discuss safety of the cox-2 inhibitors but also added there is no evidence of the entire class of drugs causing cardiovascular problems.

“We are far from understanding the complex mechanisms that lead to this toxicity,” said Woodcock, who spoke Monday at the American College of Rheumatology’s annual meeting in San Antonio.

That lack of clarity is causing many doctors to curtail their use of cox-2 and instead recommend patients take pain relievers such as aspirin and nonsteroidal anti-inflammatory drugs.

“I think we are probably better going back to aspirin and other nonsteroidal,” said Dr. Kevin Stone, founder of the Stone Clinic for Sports Medicine and Arthritis Research in San Francisco.

In the midst of all the controversy, Pfizer Inc. is launching a splashy new ad campaign to promote Celebrex that begins Wednesday. Pfizer spokeswoman Michal Fishman said the ads, which will appear in newspapers, magazines and on television, are designed to address barriers that keep arthritis sufferers from discussing pain relief with their doctors. She said one problem is that some patients associate prescription pain relievers with narcotics.

The ad tag line reads, “Celebrex. For Joint Pain. No More. No Less.” while the copy tell patients the drug isn’t a narcotic so it won’t “make you foggy” but will provide relief.

Initially, analysts had expected Vioxx’s withdrawal to be Pfizer’s gain. But now with concerns that the entire class may have the same potentially lethal side effects as Vioxx that is no longer a certainty.

Merck officials have also said often that is not appropriate to conclude that all drugs of the same class have the same side effects. That may be true but doctors and analysts say that they will be shocked if the FDA approves Arcoxia.

Analysts said even if the FDA did approve Arcoxia it wouldn’t begin to fill void left by Vioxx because so few doctors would fell comfortable using it. Vioxx accounted for $2.5 billion of Merck’s sales last year.

Arcoxia has been sold in 45 other countries since 2001 and while sales have been small– $92 million in the first six months of this year–it is unclear if foreign doctors will stop using it because of Vioxx.

British doctor Dr. Andrew Ostor said he preferred Arcoxia to the other cox-2s because it is less expensive and gentler on the stomach. But now he has cut his use of the whole class.

“The entire situation is in a state of flux,” Ostor said.

The study released Tuesday found that dropout rates due to stomach problems were more than double in the patients taking diclofenac than in those taking Arcoxia. But there was no statistical difference in adverse cardiac events.

Meanwhile, the other data released showed no increased risk when taking placebo, diclofenac or ibuprofen. When Arcoxia was compared to naproxen in the pooled analysis there was no statistical significance between the two but patients on naproxen had fewer problems. Merck has long maintained naproxen is a cardioprotective agent.

In a 2000 study, patients taking Vioxx had five times the rate of heart attacks as those taking naproxen. Many believe that study should have lead Merck to examine Vioxx’s safety profile much earlier, and hundreds of lawsuits have been filed over the drug.

Merck shares closed up 26 cents to $31.16 on the New York Stock Exchange.