Rosiglitazone--heart toxicity?

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http://www.nytimes.com/2007/05/22/business/21drug-web.html?_r=1 & hp & oref=slogin

May 22, 2007

Study Cites Safety Questions About Diabetes Drug

By

STEPHANIE SAUL

An article released today by the

New England Journal of Medicine raised safety questions about the

widely-used

diabetes pill Avandia. An analysis of clinical trials concluded that

the drug might significantly increase the risk of heart attacks.

The journal, a prestigious weekly, posted the paper on its Web site,

ahead of its print publication June 14, a step the editors take with

matters they consider to have public health importance.

The journal’s editor, Dr. M. Drazen, said: “We view this as the

best publicly available data on a very important question. It shows what

we regard as a preliminary, but worrisome, signal about cardiovascular

toxicity of this drug.”

While noting possible weaknesses in data used in the analysis, an

accompanying editorial calls for a

Food and Drug Administration review and questions why physicians

would prescribe Avandia, which is made by the British pharmaceutical

company

GlaxoKline and known generically as rosiglitazone.

The company’s stock was off more than 1 percent this morning after the

study was inadvertently published prior to an embargo. It was not

supposed to be released until 5 p.m., after the closing bell on Wall

Street. GlaxoKline scheduled a noon briefing for reporters to

discuss the article, but they did not make an immediate comment.

F.D.A. officials were not immediately available for comment.

“In view of the potential cardiovascular risks,” the editorial said, “and

in the absence of evidence of other related advantages, except for

laboratory measures of glycemic control, the rationale for prescribing

rosiglitazone at this time is unclear. ” The editorial cautioned patients

not to stop taking the medication without discussing it with their

doctors.

Dr. Drazen said patients concerned about the drug should meet with their

doctors to decide whether to remain on it or switch to another drug.

Avandia, on the market since 1999, is used by an estimated two million

people a year worldwide for the treatment of Type 2, or adult-onset,

diabetes. With $3.2 billion in worldwide sales last year, it was Glaxo’s

second-biggest product.

,.

The editorial, by Dr. Bruce M. Psaty of the

University of Washington and Dr. Curt Furberg of

Wake Forest University, said the accompanying study had once again

spotlighted flaws in the nation’s drug approval and monitoring system.

They asserted that those problems had not been fully addressed by

recently passed legislation meant to strengthen the agency’s powers.

Both Dr. Psaty and Dr. Furberg have been critical of the drug approval

process in the past.

The finding ­ that Avandia raises the risk of heart attack by 43 percent

­ was based on a review of 44 studies of the drug. The review was

conducted by Dr. E. Nissen and Kathy Wolski of the Cleveland

Clinic, where Dr. Nissen is the chief of cardiovascular medicine.

Dr. Nissen was among the first doctors to raise questions about the

cardiovascular safety of Vioxx, the

Merck painkiller that was withdrawn from the market in 2004. His

concerns about Avandia were first publicly raised last December in a

letter in the Lancet.

Dr. Nissen’s letter noted increased cardiovascular problems in a

5,000-patient clinical study, called Dream. GlaxoKline had sponsored

the Dream trial in an effort to expand the product beyond a treatment for

diabetes by using it to prevent the disease.

In the Dream trial, patients taking Avandia had 66 percent more heart

attacks, 39 percent more strokes and 20 percent more deaths from

cardiovascular-related problems. That outcome, Dr. Nissen wrote,

“virtually precludes the possibility of an overall benefit and suggest an

unexpected mechanism for harm.”

Results from another trial, Adopt, published in December, also indicated

an elevated risk of heart problems compared to another diabetes drug.