Vioxx

WASHINGTON -- A Food and Drug Administration researcher lumped five top-selling pharmaceuticals into the same category as Vioxx, the cox-2 inhibitor that Merck pulled off the market in September, when testifying before the Senate Finance Committee last month.

FDA reviewer David Graham cited Abbott Laboratories' Meridia, a weight-loss remedy; AstraZeneca's statin Crestor; Roche's acne medicine Accutane; Pfizer's cox-2 inhibitor Bextra; and GlaxoSmithKline's Serevent, an asthma remedy, as all having less-than-acceptable safety profiles.

The FDA and representatives from each of the respective companies defended those medicines as safe and effective when used as directed. "Dr. Graham's congressional testimony does not reflect the views of the [FDA], stated Steven Galson, acting director for the Center for Drug Evaluation and Research. "The five specific drugs that Dr. Graham identified in his oral testimony are currently approved as safe and effective for use in the United States."

All told, Graham discredited $1.7 billion worth of pharmaceuticals still on the market in one fell swoop, according to data IMS Health provided (year-to-date through September), and kicked off another round of debates regarding the mission of the FDA, which as potentially contradictory mandates to spur new drug development and police adverse events for those drugs that the agency already has approved.

The FDA has been accused several times this year of pandering to pharmaceutical interests, a charge that has generated concern among the senior leaders at the agency. FDA has a well-documented and long-standing commitment to openness and transparency in its review of marketed drugs," stated FDA acting Commissioner Lester Crawford in an attempt to diffuse allegations that the agency's drug review process is faulty. "Indeed, the post-market review of Vioxx ... [was] initiated and funded by FDA and managed by its Office of Drug Safety. That is evidence that the system is working," he said.

Crawford last month announced additional steps to improve the monitoring of recently approved drug products. The components of that FDA initiative include a review of the drug safety system conducted by the Institute of Medicine, the naming of a permanent director for the Office of Drug Safety and the publishing of risk-management guidances.

The stigma tying the FDA to pharmaceutical industry interests still persists, however.

"My concern is that the FDA has a relationship with drug companies that is very cozy, commented Sen. Chuck Grassley, R-Iowa, the day before the Senate hearing. That is exactly the opposite of what it should be--the health and safety of the public should be the FDA's one and only concern. "Grassley and others see a dichotomy within the FDA: Can the FDA aggressively seek to pull unsafe drugs from the market when it was the agency that approved the sale of those drugs in, the first place?

"[The] FDA's Office of Drug Safety, in the Center for Drug Evaluation and Research, is already an independent office separate from the Office of New Drugs, the office that reviews, new drug applications," said the FDA's Galson, suggesting there is no conflict of interest in the agency's dual role of shepherding drug development and policing medicines already on the market.

Indeed, the understanding that each of the medicines Graham named carries a certain risk of adverse events is not new. In fact, the safety profiles for each of those medicines have been addressed already by the FDA or currently are under review, Kathleen Quinn, an FDA spokeswoman, told Drug Store News.

Graham criticized the FDA for approving Crestor, noting that the drug carried an increased risk of renal failure. AstraZeneca has countered that Crestor carries a safety profile similar to that of the other statins on the market. "To date, the FDA has not given [AstraZeneca] any indication of a major concern regarding Crestor," the company stated. "The comments [made by Graham] are inconsistent with past public statements from the FDA and our understanding of [the agency's] current view of the safety and efficacy of Crestor."

In October, Pfizer detailed health care professionals on the safety concerns regarding its cox-2 inhibitor Bextra in light of the Vioxx recall. "Since 2002, the Bextra product label has included information regarding the risk of a very rare but serious skin reaction," the company stated, noting that the risk of that skin reaction also exists with many other medications.

Pfizer also reviewed information about the cardiovascular profile of Bextra--noting that available clinical information for Bextra suggests there is no increased risk of cardiovascular thromboembolic events in people treated for osteoarthritis and rheumatoid arthritis. Graham said the drug poses the same risk for heart disease as Vioxx did.

"Pfizer will be conducting further studies to confirm the long-term cardiovascular safety profile of Bextra in patients who require chronic treatment for arthritis with a cox-2-specific inhibitor," the company stated.

Graham suggested that the FDA should consider whether the benefits of Meridia, a weight-loss drug, actually outweigh risks of high blood pressure and stroke associated with that drug, he testified at the Senate hearing. Meridia is one drug that the agency "is continuing to monitor, Quinn remarked.

The use of the acne remedy Accutane has been linked to severe birth defects, Graham charged, stating that the drug should be removed from the market. Currently, there is a black-box warning on the product's labeling informing physicians that women who are pregnant or could become pregnant should not take Accutane.

And late last month, the FDA announced the strengthening of the risk minimization action plan for Accutane (isotretinoin) and its generic equivalents. According to the agency, the tougher action plan reflects agency and sponsors' consideration of the recommendations from a February joint advisory committee meeting.

Under the new program, sponsors will obtain registration of not only prescribers, but also pharmacies that dispense and patients who use isotretinoin. The program also includes documentation of a negative pregnancy test before prescribing isotretinoin to women who are capable of becoming pregnant.

Graham linked the use of Serevent, an asthma remedy, to deaths caused by asthma. "We've got case reports of people dying, clutching their Serevent inhaler, Graham told the Senate committee. Unlike albuterol, however, Serevent is not indicated as an emergency inhaler to be used during an acute asthma attack.

"Any issues concerning mortality associated with Serevent have been fully considered by the FDA," GlaxoSmithKline stated in a release, "resulting in a black-box warning that was included in the medicine's label in August of 2003." At that time, the agency concluded that the benefits of Serevent outweighed any potential risks involved, GlaxoSmithKline added.

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