Healthy Skepticism Library item: 9409

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Publication type: news

Harris G.
F.D.A. Panel Rejects Merck Pain Pill in 20-1 Vote
New York Times 2007 Apr 12Business
http://www.nytimes.com/2007/04/12/business/12cnd-drug.html?_r=1&oref=slogin

Full text:

GAITHERSBURG, Md., April 12 – A panel of federal drug advisers voted 20-to-1 today to reject an application by Merck to sell its pain pill Arcoxia because of concerns that the drug could cause as many as 30,000 heart attacks a year if widely used.

Food and Drug Administration officials were unusually harsh in their criticism of the medicine. “What you’re talking about is a potential public health disaster” if Arcoxia is approved for sale, Dr. David Graham, an F.D.A. safety officer, told the panel.

Arcoxia is a sister drug to Vioxx, which Merck withdrew in 2004 after a study showed that it also increased the risks of heart attacks and strokes. Merck currently sells Arcoxia in 63 countries, and the company underwrote a huge testing program that involved 34,000 arthritis patients.

The studies showed that Arcoxia causes nearly three times as many heart attacks, strokes and deaths as naproxen, a popular pain pill sold as Aleve, but was no more effective in curing pain. Patients taking Arcoxia suffered worrisome increases in blood pressure.

Dr. Peter Kim, Merck’s research chief, told the panel that the nation’s estimated 21 million arthritis patients needed new therapy options. Company representatives who followed him acknowledged that Arcoxia is no better or safer than 20 older pain pills already marketed, some for pennies a pill.

It was a tepid endorsement for a medicine that Merck had once hoped would offer arthritis sufferers significantly better and safer pain relief. Indeed, Merck executives insisted for years that the company would seek to sell only medicines that offered substantial benefits over previous therapies.

Even so, the F.D.A. forcefully disagreed with the company. And several panel members were withering in their criticism of Merck and its drug.

Dr. David Felson, a panel member from Boston University, asked Merck’s presenters if they knew on average how many patients would die if Arcoxia were sold. Dr. Felson called the number a “treat to kill” ratio. Asked several times for such a number, Merck executives never answered directly.

Dr. James Fries, a panel member and rheumatologist from Palo Alto, Calif., dismissed Merck’s argument that arthritis sufferers need a pain pill that is no different from the 20 others that they can already take. “A new drug has to have some reason” to use, Dr. Fries said.

Agreed Martha Solonche, a panel member from New York, said: “The idea should not be that we need new drugs. The idea should be that we need better drugs.”

Much of the day’s discussion centered around which of many older medicines should be compared to Arcoxia. In early studies, Merck compared Arcoxia with naproxen and found that Arcoxia was far more dangerous to the heart.

So Merck switched to diclofenac, a pain medicine that is popular outside of the United States and is widely believed to be more dangerous to the heart than naproxen. The company claimed that its trials showed that Arcoxia was no more dangerous than diclofenac.

But Dr. Robert B. Shibuya, an F.D.A. medical officer, said that if a million patients switched from diclofenac to Arcoxia, as many as 2,300 more could experience heart attacks, strokes and deaths.

The F.D.A. and its advisers have become far less tolerant of risks in medicines that offer few life-saving benefits. Just last week, the F.D.A. announced that it had requested the withdrawal of Zelnorm, an irritable bowel drug. Studies had shown that Zelnorm might increase the risks of heart attacks and strokes slightly. The drug provides so few benefits, though, that the agency would not tolerate even a slight increase in risks.

Today’s vote could end the last hopes that any new medicines similar to Vioxx and Arcoxia could get approved in the United States.

Called Cox-2 inhibitors, these drugs – which include Celebrex – were originally developed in hopes that they would be easier on the stomach than ibuprofen and naproxen.

But in safeguarding the stomach, the new drugs seemed to hurt the heart. And since almost no one would trade a heart attack for an ulcer, the underpinnings for the class of medicines seemed to disappear with Vioxx’s withdrawal.

Celebrex, made by Pfizer, had $2 billion in sales last year. But the drug’s success is a triumph of marketing over medicine. Celebrex is considered no better or safer than older pills that sell for a fraction of its price.

Arthur Levin, a panel member who is director of the Center for Medical Consumers in New York, said he wondered why the F.D.A. even called the advisory committee.

“Based on the history and based on the evidence, my question is, why are we even having this meeting?” Mr. Levin said.

The F.D.A. once used advisory committee meetings mostly to provide advice when the agency was uncertain of the right answer. Increasingly, the agency seems to be using the meetings to explain its decisions and even air some of its internal disagreements.

At one point during today’s meeting, Dr. Graham engaged in a pointed debate with two other F.D.A. officials over past F.D.A. decisions. Dr. Graham said repeatedly that “F.D.A. is wrong” in its decisions about the relative risks of older pain pills. Dr. John Jenkins, director of the F.D.A.’s office of new drugs, called Dr. Graham’s characterizations “simply false.”