Health

WITHDRAWAL PAIN

Arthritis sufferers are missing their Vioxx—and, even more, their peace of mind

ROBERT SHEPPARD November 29 2004
Health

WITHDRAWAL PAIN

Arthritis sufferers are missing their Vioxx—and, even more, their peace of mind

ROBERT SHEPPARD November 29 2004

WITHDRAWAL PAIN

Health

ROBERT SHEPPARD

Arthritis sufferers are missing their Vioxx—and, even more, their peace of mind

THEY BURST UPON the scene five years ago, grabbing the limelight with an almost shameless display of feel-good ads. A new, kinder generation of painkillers, they were hailed as “super Aspirin”—a boon for arthritis sufferers who literally could not stomach the bleeding and gastrointestinal problems of everyday analgesics. Now Vioxx, the big dog in this category, is gone, its spectacular withdrawal in late September still reverberating through Wall Street and about to hit the courts. The line of attack: when did drug giant Merck & Co. Inc. first know Vioxx could provoke heart attacks or strokes in a significant number of users? And why didn’t it do more in the early stages to follow the clues?

Adding to the drama, Vioxx’s chief rival, Pfizer Inc.’s equally promoted Celebrex, has been called on the regulatory carpet in Ottawa and elsewhere. Health Canada had Pfizer’s Montreal-based subsidiary submit the results of every study involving Celebrex and sister drug Bextra by the end of last

week, and is to take the next several weeks, maybe months, to sift through the data. The stakes are high and not just because Vioxx was a US$2.5 billion-a-year blockbuster (nearly $200 million of those sales in Canada)—a prize market now up for grabs.

Some scientists say there are enough straws

in the wind that the entire class of COX-2 inhibitors—four drugs have been licensed in Canada, of which Vioxx and Celebrex were by far the pre-eminent sellers—should be taken off the market or restricted to patients without a hint of heart disease, which would severely limit their reach to the elderly.

Pfizer calls that guilt by association, arguing that, in three large studies, there has been no empirical evidence linking Celebrex to serious cardiovascular problems the way Vioxx had been almost from its outset.

The furor, being played out almost daily in news pages even as Pfizer has cranked up its ads for Celebrex in the U.S., has rattled the confidence of Canada’s estimated four million arthritis sufferers. “I think most of my patients are a little panicky right now,” allows Dr. Arthur Bookman, an arthritis specialist at Toronto’s University Health Network. COX-2 drugs clearly filled an unmet need for those wracked by chronic pain but given to internal bleeding or kidney problems on the old painkillers. “A lot of these people are suffering now,” he says. “They felt Vioxx was the only thing that was really working for them, and they would have willingly stayed on the drug.”

On the other hand are arthritis sufferers like Jim Venables, a 49-year-old former bus

MERCK’S huge about-face has put the safety spotlight on its competitors’ productsall the other COX-2 drugs

KILLING THE COMPETITION Beginning in 1999, a new generation of painkillers called COX-2 inhibitors began supplanting the more traditional anaigesics-NSAIDS or non-steroidal antiinflammatory drugs such as Aspirin, acetaminophen and ibuprofen-for those with chronic pain.

driver in Calgary. Four months after he began taking Vioxx in the spring of2000, he had a massive heart attack that has left him unable to work. Not attributing this to the medication, he kept on with the Vioxx until it was withdrawn in September. And while he has talked with his doctor about alternatives, “to tell you the truth, Fm scared to death of all of them right now,” he says. “What have they got for side effects?”

Venables is one of several thousand Canadians suing Merck for damages in class action complaints, a list that includes former NHL goalie Rob Tallas, a Vioxx user who had a heart attack earlier this year while playing pro hockey in Finland. About a hundred Canadians are also suing Pfizer through Regina lawyer Tony Merchant. But they may have a tougher go. According to Dr. Muhammad Mamdani, a drug expert with the Institute for Clinical Evaluative Studies, there have been no studies linking Pfizer’s Celebrex to an elevated risk of heart attack. Some connections are beginning to surface for

‘I THINK most of my patients are a little panicky right now. They felt Vioxx was the only thing really working.’

Pfizer’s Bextra, also a COX-2. But these trials involved high-risk patients who were undergoing cardiac surgery, so the jury is out.

Vioxx, however, is another matter. One of the most effective of the COX-2 drugs, it had a devoted following—worldwide sales last year were US$2.5 billion, compared to US$1.8 billion for Celebrex and US$687 million for Bextra. “Even now,” says Dennis Morrice, head of the Canadian Arthritis Society, “I’m getting more calls from people asking, ‘Where can I get Vioxx? I want my life back.’ ’’But warning signs were there from the beginning.

In spring 2000, less than a year after it had been on the market, a study looking at the effectiveness of Vioxx versus another new anti-inflammatory, naproxen, found an elevated number of heart attacks in the Vioxx group. But Merck executives declined to follow up on that result, basically asserting their drug was safe until others proved the contrary. This was not an unrealistic response, notes Bookman: at the time there was speculation that naproxen might be

lowering the risk of heart attack and therefore heightening the differences between the two agents. As well, some scientists felt it would be unethical to match Vioxx against a placebo on patients at risk of heart disease, simply to test an hypothesis.

Still, there was a growing unease among some researchers—and allegations that the New Jersey-based Merck was receiving preferential treatment from U.S. regulators. It was the second largest drug company in the U.S., after all, and a darling of Wall Street. U.S. regulators rejected the accusations, and they and their Canadian counterparts forced Merck to add a heart attack warning to the Vioxx label two years ago.

That warning didn’t slow the drug’s popularity or Merck’s aggressive marketing, which included US$45 million on advertising last year alone. Nothing was going to stop this train—that is, until a recent trial of a mere 2,600 patients with colon cancer was halted after 18 months. It found 15 cases of heart attack, stroke or serious blood clotting per thousand people who were taking Vioxx—a 1.5 per cent risk, exactly double that for those on a placebo. Within days of the results, Merck withdrew its drug and turned to face the consequences: a stock plunge ripped nearly US$40 billion from its market value, and lawsuits could take a further US$10 billion.

Of course, there are risks in every daily medication. By some counts, 1,200 Canadians died each year from bleeding and other problems associated with earlier generations of painkillers. COX-2s cut that in half, offering a comfort zone for a much wider net of users and prescribing doctors that has now been almost cruelly yanked away.

In many respects, Vioxx can be seen as a victim of its own success. It was designed specifically for arthritis patients with stomach bleeding, a group that may well have accepted a slightly elevated risk of heart problems. But it was marketed as a super Aspirin, a cure-all for everything from arthritis pain to menstrual cramps. It seems to have been the most effective medication in its class, but this apparently came at a cost— the theory is it upset the delicate cell chemistry in blood vessels, tipping the balance, perhaps only slightly, from bleeding towards clotting. If that’s the case, it will be a very expensive lesson-for the pill maker and the patients—to have learned. ITO

Brian Bergman