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

WASHINGTON, Dec. 22 - 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.

I'm an infrequent fish eater (yuk, it makes the house smell fishy) and daily fish oil user. I look carefully at the composition of Omega 3s and especially want Eicosapentaenoic Acid (EPA). My guide for this is Barry Sears, author of the Zone Diet books and a high-level ivy-league biochemist who trains Olympic athletes.

If you use fish oil, you might check out Natural Factors RxOmega-3 Factors, pharmaceutical grade, with 630 mg Omega3 in each cap, 400 of which is EPA. Nice product! I found it at www.iherb.com at a very good price.

Also, because I live in the gloomy northwest, I take Cod Liver Oil in the winter, buy Carlson's Norwegian 1000 mg, supposedly the most pure product available. So that also gives me an additional 240 mg of Omega 3. Also available at iherb.com at a nice discount.

And to think I used to live in Florida and had a vacation house in Key Largo. Who worries about fish oil there?

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.

Though I am concerned with the Statins as I am with almost any drug with an advertising budget bigger than some small nations' GDP the above statement seem like a hyperbolic extrapolation. Still it would be interesting to see the unmodified data from the original trials.

I have the Sears book on Omega 3's.

An excellent source of Omega 3's (DHA and EPA) is available from most SuperWal-Marts. Look in the egg section for "Christopher Eggs".

Each egg has 600 mg of DHA and EPA. That is the same as two standard fish oil concentrate pills.

It is, by far, the highest non-fish source of the converted Omega 3's I've ever seen (plant sources are ALA and converted at 10-15% efficiency to DHA and EPA).

http://christophereggs.com/

Hello guys,

I thought I'd chime in with a little insight (hopefully!).

Regarding Natural Factors fish oil, it IS pharmaceutical-grade, but it's in "ethyl ester" form, rather than the natural "triglyceride" form, which means its absorption by the body is severely impaired. Regarding cod liver oil, it contains toxic levels of vitamin A, so in the winter, I'd make sure you balance it with another fish oil, or just take a Vitamin D supplement in place of the Cod Liver Oil (The nutrient that sunlight produces). Also, Carlson's claims their fish oil is pure, but they don't test every batch with the International Fish Oil Standards program.

Those Christopher eggs are interesting, but I don't see any mention on their website that they contain DHA and EPA. It just says Omega-3s, but what kind of omega-3s is conspicuously absent. Since the omega-3s come from feeding their hens all-vegetarian diet, I think it's safe to assume that it's ALA, the short chain omega-3s, rather than the long-chain EPA and DHA that are useful to your body.

I operate a website about the benefits of fish oil supplements and I also have a report that goes into more detail about ethyl esters vs. triglycerides, cod liver oil, international fish oil standards, short and long chain fatty acids, and other things about fish oil. You can request the report by e-mailing me at marshall@fishoilblog.com if you'd like.

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