NEWS - FDA whistle-blower Graham blasts new Merck arthritis drug

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FDA whistle-blower Graham blasts new Merck arthritis drug

Updated 9/12/2006 9:51 PM ET

By Rita Rubin, USA TODAY

The arthritis drug that Merck has developed to compete with Celebrex

may be as risky for the heart as Vioxx, writes Food and Drug Administration

whistle-blower Graham in an editorial posted online Tuesday by a

medical journal.

In considering whether Arcoxia should be approved, " the FDA, academia,

and the medical research enterprise are once again faced with the

opportunity to forsake common sense by willfully accepting misdirection and

disinformation presented in the guise of science, " Graham writes on the

Journal of the American Medical Association's website.

An editor's note says the FDA allowed Graham to write the editorial as

a private citizen, not as an agency employee. The editorial and the two

studies it accompanies will run in the Oct. 4 JAMA, but they were posted

online early " because of the public health implications, " a JAMA press

release says.

Graham, a physician in the FDA's Office of Drug Safety, made news

nearly two years ago when he told a Senate panel that the agency was

" virtually defenseless " in preventing a " tragedy and profound regulatory

failure " such as Vioxx.

Concerns for cardiovascular safety had spurred Merck to stop selling

Vioxx in September 2004.

Like Vioxx and Celebrex, Arcoxia is a so-called COX-2 inhibitor. Their

selling point has been a lower risk of bleeding stomach ulcers and other

serious digestive tract complications than other non-steroidal

anti-inflammatory drugs, or NSAIDs, such as ibuprofen.

A month after Vioxx was taken off the market, the FDA issued an

" approvable letter " for Arcoxia, its successor, asking for more data on

safety and effectiveness. The FDA still has not made a final decision on

Arcoxia, which is sold in 62 countries.

In an August paper in the American Heart Journal, Merck scientists

reported that preliminary analyses of clinical trial data showed that the

rate of cardiovascular " events, " such as heart attacks, was similar between

Arcoxia and diclofenac, an older arthritis drug.

But one article posted online by JAMA raises serious questions about

the cardiovascular safety of diclofenac, which, in turn, raise questions

about the safety of Arcoxia. Researchers pooled the results of 23 studies in

which people decided whether to take an NSAID. They found that diclofenac

raised cardiovascular risk as much as lower-dose Vioxx. Only higher-dose

Vioxx was riskier.

Co-author Henry, a clinical pharmacologist at the University of

Newcastle in Australia, says he has switched patients from diclofenac to

naproxen, which, in his study and others, appears to be the only NSAID that

doesn't raise cardiovascular risk. " It causes gastrointestinal bleeding, no

question, " he says. " But I'd rather have a gastrointestinal bleed than a

heart attack. "

For that reason, says Wake Forest University medical epidemiologist

Curt Furberg, the FDA should pull diclofenac off the market and remove the

" black box " warning about cardiovascular risk, which the FDA ordered on all

NSAIDs in April 2005, from naproxen's label.

" The take-home message is stay away from diclofenac, which is

basically another way of saying that Arcoxia is harmful, " says Furberg, who

sits on the FDA's Drug Safety and Risk Management Advisory Committee.

In a statement, Merck said the results of the Arcoxia/diclofenac

comparison " are consistent with FDA's April 2005 memo stating that long-term

clinical trials have not shown a difference in cardiovascular safety "

between COX-2s and other NSAIDs, " with naproxen as a possible exception. "

A second paper on JAMA's website pooled the results of 114 clinical

trials in which volunteers were randomly assigned to take a COX-2 inhibitor

or another NSAID or a placebo. Only Vioxx was found to raise the risk of

heart rhythm abnormalities and kidney-related problems.

Co-author Ding, a doctoral candidate at the Harvard School of

Public Health, cautions that the finding does not necessarily mean Arcoxia

and Celebrex are safe.

" I just want to say that in the (COX-2) class analysis, Vioxx seemed

to stand out, " Ding says.

http://www.usatoday.com/news/health/2006-09-12-merck-drug_x.htm

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org