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Thursday, April 12th 2007

Vioxx's Replacement Gets A Beat Down

Merck’s “new” COX-2 inhibitor got flatly beat down by the FDA today:

If Acroxia Could Talk
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The panel fielding the question on whether to approve the pain killer in the U.S. voted 20 to 1 against it! Okay, it isn’t that shocking, as we’ll see this was expected. But still, 20 to 1!

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.

This is a little bit of an offbeat comparison. Mind you it is a comparison which Merck itself undertook,

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.

Consider that naproxen is by prescription only in most of the world, but in the U.S. a twelve year old can walk out of the grocery store with bottles of Aleve. Meanwhile, ectoricoxib (Acroxia) is available by prescription in plenty of countries but not in the U.S (ed: according to Consumer Affairs it is available in 62 countries).

Clearly the FDA knows something a good chunk of the world doesn’t?

That isn’t to say I disagree with the decision on Acroxia. Without reading anything but what is published by the NY Times, it is hard to disagree with the conclusions of the panel,

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.”

This conclusion on Acroxia has been coming for months and months. From Consumer Affairs back in September 2006,

David Graham, a Food and Drug Administration insider, claims the new drug, Arcoxia, may be as risky for the heart as Vioxx.

Graham aired his concerns in an editorial posted on the Journal of the American Medical Association’s website. In characteristically blunt language, Graham accused the pharmaceutical giant of engaging in “misdirection and disinformation presented in the guise of science.”

Here’s Dr. Graham’s editorial (free with registration).

There is no real surprise with the panel’s findings. But I suppose it brings up an oppurtunity for what I think is a real question. What do we want government’s role to be in the whole drug business. Do we really want them running the risk vs. benefit analysis for us? “Well, we can see absolutely no circumstances anytime, why any doctor or his patient would want to use this drug…so phoey with it!”

I mean the rhetoric the FDA panel members spit out is lovely. You read it at first and say “No one can disagree with this!” But, while popping pills is a dangerous business, just how paternalistic do we want the government to be? I bend libertarian often, so we know my leanings on the issue. And those leanings aren’t so unrealistic.

What is spelled out in the NY Times certainly isn’t the only way to do their job, despite what some might claim. We could label some threshold for a drug’s risk for serious morbidity and mortality and determine a drug’s approval solely on that without trying to decipher whether it has actual uses (which is, to me, the sillier exercise).

It is true that the COX-2 inhibitors don’t appear to be more efficacious than non-selective NSAIDS.

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.

We’ve seen as much in celecoxib versus naproxen and diclofenac [1] and this review piece from 2005 by a rheumatologist [2].

A general acceptance has emerged of the fact that COX-2 inhibitors are not super efficacious. Even if large, but outlying studies, like this Canadian one which showed osteoarthritis patients were more likely not to switch painkillers when using a COX-2 selective NSAID versus a non-selective NSAID (and thus, by implication, were more satisfied with the COX-2 inhibitors) [3].

Even with that being a near consensus about this specific battle (over NSAIDS) I’m still not sure I buy the New York Time’s implication, by lines like that one above, that drug approval should somehow be based on usefulness and cost effectiveness.

Clearly there are people in the world who find comfort in ectoricoxib. Pining for a utilitarian benefit/usefulness analysis of a drug is dangerous in how it limits patient’s options sometimes. Maybe not in this instance; despite the line above about patients finding comfort in extoricoxib, I’m trying to speak in general terms.

In anycase, give it a thought and drop comments if you have an opinion.


1) Singh, Gurkipal, et al, “Celecoxib Versus Naproxen and Diclofenac in Osteoarthritis Patients: SUCCESS-I Study,” American Journal of Medicine 119: 255-266

2) Hochberg, Marc C. “COX-2 Selective Inhibitors in the Treatment of Arthritis: A Rheumatologist Perspective,” Current Topics In Medical Chemistry, 2005 5: 443-448.

3) E. Rahme , Y. Toubouti , and E. Hunsche, “Therapy switching and associated costs in elderly patients receiving COX-2 selective inhibitors or non-selective non-steroidal anti-inflammatory drugs in Quebec, Canada” Rheumatology 45: 903-910.

[Wikipedia: Etoricoxib]
[Wikipedia: Naproxen]