FDA, Drug Companies Deny Oversight Flaws

WASHINGTON —  Federal regulators and pharmaceutical companies sought to ease concerns Friday over alleged flaws in the drug oversight system and the risks of five medications in particular.

“We categorically reject” assertions that the Food and Drug Administration failed to protect the public, Dr. Steven Galson, head of the agency’s drug evaluation branch, said on NBC’s “Today.” Manufacturers of the five medications issued statements attesting to the drugs’ safety when properly used.

The activity Friday came in response to dramatic public testimony Thursday from one of the FDA’s drug safety reviewers, who told a Senate committee that the agency had left the nation “virtually defenseless” against dangerous medications and that five widely used drugs deserved reconsideration.

The Senate hearing had been called to discuss a sixth medication, the blockbuster painkiller Vioxx, which manufacturer Merck & Co. was forced to pull from the market Sept. 30 after data showed it raised the risk of heart attacks among people taking it for at least 18 months.

Dr. David J. Graham, a 20-year FDA employee who reviews drugs already approved for patient use, told the Senate Finance Committee hearing that the FDA was “incapable” of ensuring that unsafe drugs such as Vioxx were kept off the market. Graham said there were significant safety concerns with five drugs still in wide use: Accutane, an acne medicine; the painkiller Bextra; the cholesterol-lowering drug Crestor; Meridia, which is taken for weight loss; and Serevent, an asthma drug.

In a statement on the FDA’s website Friday, Galson said the five drugs were “safe and effective,” although the agency continues to monitor possible risks. All drugs have risks, which must be weighed against their benefits, Galson said.

As for Graham’s testimony, it “does not reflect the views of the agency,” he added.

Although the manufacturers of the five drugs offered safety assurances Friday, an FDA official noted that the agency had started action to reduce potential risks of two of the drugs, Accutane and Bextra. In Europe, regulators said they were investigating concerns about safe dosage for Crestor patients.

Merck, whose stock has been battered by the Vioxx debacle, took out three full-page ads in the Wall Street Journal, defending its actions and emphasizing its reputation for quality. “For 100 years, patients first,” said the headline on one of the ads.

Some critics have been raising concerns about several of the drugs for years. They also have said that the FDA had become a less stringent watchdog for pharmaceutical problems ever since Congress enacted changes in the 1990s aimed at bringing new drugs to market more quickly.

One consumer group, Public Citizen’s Health Research Group, had written to the FDA twice this year asking that it remove Crestor from the market because of what it called a high risk of kidney problems.

But on Friday, reaction among physicians and investors to Graham’s testimony was muted, though noticeable.

Shares of the companies that make the five drugs Graham cited all lost ground. But the declines were not a great deal worse than those in the broader market, which had a rough day after Federal Reserve Chairman Alan Greenspan made worrisome remarks about the U.S. budget and trade deficits.

Physicians said Graham’s comments caused them some concern, but many doctors were left shrugging over risks they said they already knew and were already monitoring.

All five drugs that Graham named had been the subjects of safety debates, said Bill Soller, a consumer safety expert at the UC San Francisco School of Pharmacy.

“If he truly believes that there is significant risk that should change the way these drugs are marketed, he should put that together and present it,” Soller said of Graham.

Some doctors reported calls from anxious patients. Dr. Bill Howell, an internist and endocrinologist at USC’s Keck School of Medicine, said, “I need to dive into the computer and find out what various professional organizations are saying about this. It’s part and parcel of the profession we chose.”

Howell said he would need to know more before altering his prescribing practices.

However, the FDA is planning to announce stronger safeguards to prevent women who are pregnant, or planning to have a child, from using Accutane, said an agency official who spoke on condition of anonymity because of agency policies.

On the market for more than 20 years, Accutane has been shown to cause birth defects. It is also sold under its generic name, isotretinoin.

Literature about the acne medicine carries this warning: “Causes Birth Defects -- Do Not Get Pregnant.” Government and industry have launched a campaign to keep the drug from being prescribed to women who could become pregnant. An Accutane registry for doctors, pharmacies and patients is under development.

Accutane “has been used safely and effectively for over 22 years by more than 13 million patients worldwide,” said Roche, its manufacturer, in a statement Friday.

Critics also have warned of a link between Accutane use and suicidal behavior among teenagers, but company spokeswoman Carolyn Glynn said no scientific connection had been established.

The FDA official also said the agency was planning to focus on the risks of the painkiller Bextra and similar drugs at a scientific advisory committee meeting to be held early next year. Bextra is of the same class of drugs as Vioxx, and the meeting is intended to address concerns about that group of medications generally.

Such an advisory process could lead to additional warnings, as was the case last month when the FDA told drug companies to put a vivid warning on antidepressants to alert doctors that the medications could increase suicidal thoughts and behavior in children and teens.

Pfizer Inc., which makes Bextra, said it looked forward to participating in the upcoming scientific panel. The company said no increased risk of heart problems was found in a recent study of 8,000 arthritis patients treated with the drugs for periods lasting as long as a year.

“Bextra has been found safe and effective when used as indicated,” said the Pfizer statement. The company has said its drug is a different chemical than Vioxx.

Dr. Joshua Prager, director of the California Pain Medicine Center at the UCLA Medical Plaza, said that there had been recent reports of strokes and heart attacks in patients taking Bextra, but that those patients had taken the drug after heart bypass operations.

Prager questioned whether the findings would hold for those who were not at risk of heart attacks.

Crestor, manufactured by AstraZeneca Pharmaceuticals, is used to lower cholesterol. “AstraZeneca is confident in both the safety and the efficacy of Crestor,” a company statement said. Crestor belongs to a class of drugs known as statins, which inhibit the synthesis of cholesterol in the body and reduce the risk of heart attacks.

Graham had told the Senate Finance Committee on Thursday that Crestor can cause kidney failure and that patients “do quite well” on other cholesterol-lowering medications.

In a statement issued to the stock exchanges, AstraZeneca said senior FDA officials had assured it that they did not share Graham’s concerns.

But European regulators may. Reuters reported that the European Medicines Agency, the FDA’s equivalent there, is investigating whether patients taking Crestor should start on the lowest possible dose to see how well they tolerate the drug.

Several U.S. doctors said they had reviewed the data on kidney failure from taking Crestor and found it showed no greater risk than other statins.

“Physicians are always in a position of making a risk-benefit analysis,” said Dr. John Kane, director of the Cardiovascular Research Center at UC San Francisco. “If you’ve had one or two heart attacks, then the clinical benefit expected from this drug would far outweigh the likelihood of these side effects.”

Abbot Laboratories, maker of the weight-control drug Meridia, took issue with Graham’s assertion that most patients cannot tolerate its side effects, which may include an increase in blood pressure and heart rate.

“Obesity remains one of the leading health epidemics in the U.S., and Meridia is one of the few effective drugs that are currently available for the treatment of obesity,” the company said in a statement.

Several obesity experts said they did not believe there was reason to be concerned about Meridia, because its effects on blood pressure and heart rate were well known. “If they’re one of the people who has an increase in blood pressure, we stop it -- that’s the end of it,” said Dr. Louis Aronne, director of the weight control program at Cornell’s Weill Medical College in New York.

GlaxoSmithKline, which makes the asthma drug Serevent, said it “stands firmly behind” the medication. While rare cases of serious asthma attacks and even death have been reported, the risks were addressed by a prominent label warning issued by the FDA last year, it said. That represents the strongest caution the agency can provide.

Times staff writers Rosie Mestel, Alan Zarembo and Martin Zimmerman in Los Angeles and Emma Schwartz in Washington contributed to this report.