FDA Asks AstraZeneca To Pull Crestor Ad Because of Misleading Claims About Drug’s Safety

An FDA letter to AstraZeneca states that a full-page nationwide newspaper advertisement campaign asserting the safety and effectiveness of AstraZeneca's cholesterol-lowering drug Crestor contains "false or misleading" claims and should no longer be disseminated, USA Today reports (Rubin, USA Today, 12/23). AstraZeneca ran the advertisements from Nov. 23 to 29 after FDA safety officer David Graham during a Senate Finance Committee hearing -- which addressed the recent market withdrawal of Merck's COX-2 inhibitor Vioxx -- testified about concerns he had with other drugs on the market (Henderson, Boston Globe, 12/23). Graham testified that FDA, "as currently configured, is incapable of protecting America against another Vioxx" because of ties between agency reviewers and the pharmaceutical industry. In addition, Graham cited five prescription drugs currently on the market that present significant safety risks to consumers (Kaiser Daily Health Policy Report, 12/16). Graham listed Crestor as one of the five drugs "to be seriously looked at," the New York Times reports (Harris, New York Times, 12/23). Graham said that Crestor is the only statin that causes acute kidney failure. He also said Crestor carries a higher risk of rhabdomyolysis, a muscle disorder, than other statins (USA Today, 12/23). During the first year Crestor was approved in the United States, there were 29 reports of kidney problems among people taking the drug, according to an analysis by not-for-profit consumer advocacy group Public Citizen. Such a rate indicates that the drug carries 75 times the risk for kidney problems compared with all other statins combined, according to Public Citizen representatives. AstraZeneca officials have asserted that Crestor might improve kidney function. Crestor's market share of new statin prescriptions following the hearing decreased from 8.2% to 6.4% -- a 22% decline, according to J.P. Morgan analysts (New York Times, 12/23).

Ad Content
In response to Graham's testimony, AstraZeneca published advertisements in several newspapers -- including the New York Times, the Wall Street Journal, the Washington Post and USA Today -- citing FDA's Web site and stating, "The scientists at the FDA who are responsible for the approval and ongoing review of Crestor have, as recently as last Friday (Nov. 19), publicly confirmed that Crestor is safe and effective; and that the concerns that have been raised have no medical or scientific basis" (USA Today, 12/23). The ad also said that "FDA has confidence in the safety and efficacy of Crestor" and added that Crestor "lowers bad cholesterol better than the leading medications in its class" (New York Times, 12/23). The ad also contained text that said, "A medication can be more effective and just as safe." AstraZeneca discontinued the advertisements in November, company spokesperson Emily Denney said (USA Today, 12/23).

Ad Inappropriately States FDA Position, Letter Says
In the letter to Mark Szewczak, AstraZeneca's director of promotional regulatory affairs, FDA official Christine Hemler Smith states, "The 'patient safety' print ad makes false or misleading safety claims that minimize the risks associated with Crestor, thereby suggesting that Crestor is safer than has been demonstrated by substantial evidence or substantial clinical experience." The letter also references comments during the Senate hearing from Steven Galson, acting director for the FDA's Center Drug Evaluation and Research. Galson said that FDA "has been very concerned about Crestor since the day it was approved, and we've been watching it very carefully" (Schmid, AP/Los Angeles Times, 12/23). The letter also says that the ad is "misleading because it minimizes the risks associated with the 40 mg dose of Crestor." According to the letter, AstraZeneca agreed to recommend a 40-milligram dose of the drug for those patients who could not lower their cholesterol with a 20-milligram dose. The letter continues, "FDA 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 (New York Times, 12/23). In the letter, FDA asks AstraZeneca to "immediately cease the dissemination" of the advertisement (AP/Los Angeles Times, 12/22). The letter requires that AstraZeneca respond in writing by Jan. 7 (Boston Globe, 12/23). The company posted the letter on its Web site on Wednesday (USA Today, 12/23). FDA since September has sent nine warning letters to drug manufacturers alleging false advertisement practices. However, most letters are related to exaggerations about a drug's benefits or underplaying its risks. Letters do not usually criticize a company for misrepresenting FDA.

Response
Denney said, "We stand behind the ads and our communications around Crestor. 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" (New York Times, 12/23). She added, "We really felt it was necessary to try to set the record straight" (Boston Globe, 12/23). Sidney Wolfe, director of Public Citizen's Health Research Group, said the advertisements "are just misrepresenting FDA's position, making it appear that even FDA cleared the drug; that's a lie." Wolfe speculated that AstraZeneca would soon be required to withdraw Crestor.

Implications
Sales of Crestor in the first nine months of this year were $596 million. Analysts had once estimated that Crestor would have sales of $1 billion this year and as much as $4.5 billion in 2007. AstraZeneca's profit also has been hurt in recent months by FDA's rejection of Exanta, the company's stroke-prevention medication. In addition, AstraZeneca officials last week announced that the company would stop promoting its cancer drug Iressa to physicians after clinical trials showed it did not improve patients' length of survival (New York Times, 12/23).