FDA whistle-blower blasts new Merck arthritis drug

[Guest guest]

FDA whistle-blower Graham blasts new Merck arthritis

drug

 

By Rita Rubin

USA Today

Wednesday, September 13, 2006

 

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

David 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 David 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 Eric 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.

 

PERSCRIPTIONS FOR SELECTED PAIN RELIEVERS

(in millions)

 

Celebrex 14.3

Naproxen 13.3

Diclofenac 5.5

 

Note: 2005 figures. Celebrex is a COX-2 inhibitors;

diclofenac and naproxen are another type of

non-steroidal anti-inflammatory drugs, or NSAIDs.

 

Source: IMS Health

 

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

 

 

Jai Maharaj

Om Shanti