Healthy Skepticism Library item: 813

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Publication type: news

Wilde MATHEWS, Hensley S.
Merck May Return Vioxx to Market Move Depends on Whether FDA Panel Decides Risks Exist in Similar Medicines
THE WALL STREET JOURNAL 2005 Feb 18

Full text:

Merck & Co. said it will consider returning its withdrawn painkiller Vioxx to the market if a Food and Drug Administration advisory committee decides that the risks of the drug also are found in similar medicines.

Speaking to the panel, Merck research head Peter S. Kim said that “if the advisory committee and the FDA conclude that the benefits of this class outweigh the risks in some patient populations, then we would have to consider the implications of these new data given the unique benefits Vioxx offers.”

The company withdrew the drug in September after a trial showed long-term use was tied to a risk of heart attacks and strokes.

A reversal of that withdrawal would be a shocking turn of events after one of the biggest drug withdrawals in U.S. history. Nevertheless, there are strategic reasons why Vioxx’s return to the market might be a wise move for Merck. The Whitehouse Station, N.J., company could benefit in its court fights if it were able to continue to argue that Vioxx held enough benefit to be worthwhile for some patients.

In addition, revenue from sales of the drug, even if sharply reduced, could be a boon to the company’s finances. Further, Vioxx’s revival would help Merck make a case for its similar drug, Arcoxia, which hasn’t been approved in the U.S.

Merck warned that it “has not altered its position on the voluntary withdrawal of Vioxx” and “anything further would be speculation.”

Dr. Kim’s comments, which came during the panel’s second of three days of deliberations on the safety of painkilling drugs, appeared to be part of an orchestrated rollout. After Dr. Kim offered his remarks last night, company representatives quickly offered a printed version of the statement to reporters.

The company had begun setting the stage for the idea in a presentation to the panel Wednesday, when a Merck scientist emphasized that the company had withdrawn the drug because it believed the risks were unique to Vioxx, but that it now felt the risks could be an effect of the entire class of similar drugs.

In response to a question from a committee member last night, Dr. Kim said the company withdrew Vioxx “based on the information that was available to us at that time, knowing there were alternative therapies.” Now, he said, “we’re no longer dealing with a situation where Vioxx is unique in its cardiovascular risk” but appears to be a member of a class of drugs that hold similar concerns.

The FDA, which never pressed Merck to pull Vioxx — the move was made voluntarily and presented to the agency as a fait accompli — has signaled that it would be willing to consider a re-entry to the market for the drug. Indeed, it asked the advisory committee about the risk-benefit ratio for Vioxx just as it did with competing drugs that remain on the market.

In any return to market, Vioxx undoubtedly would face tough new label warnings and possibly other restrictions that also could apply to other drugs in the same class of so-called Cox-2 inhibitors. Indeed, Merck offered its thoughts on the return of Vioxx as members of the FDA advisory committee were coming to an apparent consensus that signals of cardiovascular risk weren’t limited to Vioxx and likely also applied to other Cox-2 drugs such as Pfizer Inc.‘s Bextra and Celebrex. Still, they struggled over which medications truly carried that risk and what to do about it.

European regulators, meanwhile, yesterday took their own action against Cox-2 inhibitors. Europe’s chief medical regulator said it had concluded that Cox-2 drugs carry an increased risk of cardiovascular problems and imposed stronger warnings on the labels of all of the drugs.

The European Medicines Agency advised doctors to prescribe the lowest possible dose and shortest course of treatment to all patients taking Cox-2 inhibitors, and said the pills shouldn’t be given to people who have had a stroke or coronary-artery disease.

In the U.S., the FDA’s advisers may have a tough time focusing solely on the Cox-2 drugs. Yesterday, FDA drug-safety researcher David Graham, who has been a public critic of his own agency, raised questions about some drugs that hadn’t yet been in the spotlight — particularly Mobic and an older painkiller called indomethacin.

Based on data drawn from a database of California Medicaid patients, the research found that people taking Mobic, marketed by Abbott Laboratories, of Abbott Park, Ill., and Boehringer Ingelheim GmbH, had a 37% higher rate of heart attacks than those who hadn’t recently taken a similar painkiller. For indomethacin, an older drug available generically, the rate was 71% higher.

The new data presented by Dr. Graham put a spotlight on older painkillers that aren’t considered Cox-2 inhibitors. Part of the problem is that drugs don’t always fall fully into one category; some may behave somewhat like Cox-2 drugs but not be considered fully part of the class. The data offered yesterday by Dr. Graham, from a study he did with Stanford University adjunct clinical professor Gurkirpal Singh, included the fact that when they lumped together the painkillers, excluding Celebrex, Bextra and Vioxx, the group was linked to a 12% higher risk of heart attacks compared with taking no similar drug recently.

Paul Fonteyne, executive vice president of Boehringer Ingelheim, said the company has “observed no trend of increased cardiovascular events with our postmarket experience data” for Mobic, and that the company hadn’t seen the new analysis. Merck didn’t respond to requests for comment on Indocin, a branded form of indomethacin.

The new California Medicaid study, which hasn’t been published or peer-reviewed, also reaffirmed the evidence of Vioxx’s risks, particularly at high doses, Dr. Graham told the committee. He also concluded that at high doses, Celebrex held “probable increased risk.” Pfizer, in its presentation, said its trials showed no solid evidence that Celebrex was tied to cardiovascular problems.

In a broad discussion that also touched on broader policy issues surrounding the FDA’s role in drug safety, several members of the committee said they were convinced there was a risk tied to all Cox-2 inhibitors. The chairman of the panel, Vanderbilt University Professor Alastair Wood, said he “sees a cardiac effect” for Bextra, “certainly from Vioxx, and probably for Celebrex.” Later, he said it was “highly improbable” that some of the drugs would have been approved if the FDA had all the safety data it now has. Several panel members said the problem might not be limited to just the drugs that had been marketed as Cox-2 inhibitors. A “class effect” warning for Cox-2 inhibitors and the older painkillers would affect more than 20 drugs. Some committee members appeared to endorse that idea.