New York Times
December 23, 2004

F.D.A. Calls Ads for Cholesterol Pill Crestor 'False and Misleading'
By GARDINER HARRIS

WASHINGTON - AstraZeneca's recent full-page newspaper advertisements
defending the safety of its cholesterol-lowering pill, Crestor, are
"false and misleading," in part because serious concerns remain about
the safety of the drug, federal drug regulators said Wednesday.

The advertisements stated that "the F.D.A. has confidence in the
safety and efficacy of Crestor" and that the agency "as recently as
last Friday publicly confirmed that Crestor is safe and effective."
Neither is true, said a letter from the Food and Drug Administration
to AstraZeneca.

In fact, days before the advertisements ran, top agency officials were
widely quoted expressing concerns about Crestor's safety. Public
Citizen, a health advocacy group, has called for Crestor's withdrawal.

AstraZeneca stopped running the advertisements in November, well
before receiving the drug agency's letter, said Emily Denney, a
company spokeswoman. "We stand behind the ads and our communications
around Crestor," Ms. Denney said.

Dr. Sidney Wolfe, director of Public Citizen's health research group,
said the company's ads "are just misrepresenting F.D.A.'s position,
making it appear that even F.D.A. cleared the drug; that's a lie." Dr.
Wolfe predicted that the company would soon be forced to withdraw
Crestor.

Since September, the Food and Drug Administration has sent out nine
letters warning companies about false promotions. Most such letters
scold companies for exaggerating a drug's benefits or underplaying its
risks. Rarely does such a letter criticize a company for
misrepresenting the agency itself.

AstraZeneca's advertising campaign defending Crestor was begun after
Dr. David J. Graham, a safety official at the drug agency, told a
Congressional panel on Nov. 18 that Crestor was one of five currently
marketed drugs whose safety needed "to be seriously looked at."

Dr. Sandra Kweder, deputy director of the agency's office of new
drugs, told the panel that Crestor's risks were "something that we are
in the process of and have been evaluating very, very closely."

That same day, Dr. Steven Galson, acting director of the agency's
center for drug evaluation and research, was quoted in The Washington
Post as saying that the agency "has been very concerned about Crestor
since the day it was approved, and we've been watching it very
carefully."

The concerns largely revolve around Crestor's effect on the kidneys.
According to an analysis by Public Citizen, there were 29 reports of
kidney failure or insufficiency among patients given Crestor in the
first year of its approval in the United States. Considering the
limited number of prescriptions for the drug, that is 75 times the
rate of kidney failure or insufficiency for all other similar drugs
combined, Public Citizen said. The company responded that Crestor
might actually improve kidney function.

The remarks by Dr. Graham and others created widespread concern among
patients and physicians. In the week after the hearing, Crestor's
share of new prescriptions among cholesterol-lowering drugs tumbled 22
percent, to 6.4 percent from 8.2 percent, according to information
provided by J. P. Morgan.

So AstraZeneca placed full-page advertisements in newspapers across
the country for several days. Crestor's decline in prescriptions then
stopped. The drug's share of new prescriptions among
cholesterol-lowering drugs has remained steady at about 6.4 percent in
recent weeks.

But the advertisements were false, the drug agency wrote in an undated
letter to Mark R. Szewczak, AstraZeneca's director of promotional
regulatory affairs. For instance, they had a boldface line that
stated, "A medication can be more effective and just as safe."

The advertisements went on to claim that Crestor "lowers bad
cholesterol better than the leading medications in its class."

The Food and Drug Administration's letter, written by Dr. Christine
Hemler Smith, stated, "This claim is misleading because it minimizes
the risks associated with the 40 mg. dose of Crestor." AstraZeneca,
the letter says, agreed to reserve the 40-milligram dose for those
patients who failed to lower their cholesterol with a 20-milligram
dose.

"F.D.A. is not aware of substantial evidence or substantial clinical
experience demonstrating that all doses of Crestor are 'just as safe'
as other" cholesterol-lowering drugs, the letter states.

Similarly, the agency took issue with the advertisements' claim that
the drug agency had endorsed Crestor's safety.

Asked how the company could state in its advertisements that the drug
agency had confirmed the safety of Crestor when the agency's top
officials were saying that they were concerned about the drug, Ms.
Denney said, "We believe that our communications have been consistent
with what has been communicated to us and with what clinical trials
tell us and post-marketing data tells us."

AstraZeneca executives once had high hopes for Crestor. Analysts
predicted that sales would top $1 billion this year and reach $4.5
billion by 2007. But through the first nine months of this year,
Crestor sales were $596 million.

With $9.2 billion in sales last year, Lipitor, by Pfizer, is the
category's biggest seller, followed by Zocor, by Merck, which had $5
billion in sales, and Pravachol, by Bristol-Myers Squibb, with $2.8
billion.

Adding to AstraZeneca's woes, an Food and Drug Administration advisory
panel recently voted against approving Exanta, a stroke-prevention
drug. And the company reported last week that a large study of its
cancer drug, Iressa, showed that it did not improve survival rates of
patients. In the study's aftermath, the company said it would stop
promoting Iressa to physicians, and the drug agency said it was
considering forcing the drug's withdrawal.

The company has promised to overhaul its drug development efforts, and
it is fiercely defending the image of Crestor.