Epilepsy Drugs Draw Industry Defense
Companies Lobby FDA
Not to Add Warnings
On Suicidal Behavior
By ALICIA MUNDY and AVERY JOHNSON
June 4, 2008
WASHINGTON -- Drug companies are scrambling to try to convince the Food and Drug Administration not to add warnings for suicidal behavior risks to a large class of epilepsy drugs also used widely for a variety of other conditions.
On Monday, at a closed meeting of epilepsy researchers and industry representatives in New York, the FDA presented data that agency officials said show a statistically significant difference in suicidal tendencies for patients who have taken one of 11 epilepsy drugs that are on the market. However, the difference is quite small; the risk of suicidal behavior for patients on a placebo was 0.23% and for those taking one of the 11 drugs it was 0.37%.
Several companies at the forum held by the Epilepsy Study Consortium expressed concern to the FDA that its analysis is flawed because it grouped the results of 199 previously completed clinical studies of the 11 drugs, some of which are very different. In addition, several of them are commonly used in combination.
Three firms -- GlaxoSmithKline PLC, UCB SA and Pfizer Inc. -- made presentations at the event.
Several executives said they left Monday's conference convinced the FDA may announce new warnings about suicidal behavior soon, according to two people who attended. The FDA has scheduled an advisory committee meeting on the drugs for early July.
"We did not see a signal for suicidality at all in our data base," said Steve Romano, vice president-global health at Pfizer, which makes the drug Lyrica. He attended the meeting.
Drug makers and the FDA find themselves increasingly at odds as the agency has recently responded to criticism by toughening product labels and turning down some of the industry's biggest hopefuls. Pfizer in particular has much to lose from any change to Lyrica's label. The world's largest drug maker by sales has just watched a stricter FDA label for antismoking pill Chantix erode prescriptions of that once-hot product.
The company is struggling to convince investors that it can keep sales growing after cholesterol fighter Lipitor faces generics, as soon as 2010, and Lyrica figures prominently into that strategy. Because Lyrica has broad applications beyond epilepsy, a toughened label could curb sales across the drug's indications.
Lyrica is one of the lone bright spots in Pfizer's arsenal of new medicines. A stringent FDA warning could cripple its brisk growth. Lyrica brought in $1.8 billion in sales in 2007, and was approved last year to treat a mysterious and controversial pain condition called fibromyalgia. Other epilepsy drugs are also used to treat chronic pain, migraines, anxiety and bi-polar disorder, spurring sales globally.
Catherine Arnold, a Credit Suisse analyst, estimates that Lyrica will be a $5.6 billion blockbuster in 2015. But more bad news could bring that number back to earth: "I think the market would look at a stronger FDA label for Lyrica as very bad, especially after we've watched Chantix prescriptions take a hit," she says.
In New York Stock Exchange 4 p.m. composite trading, the New York drugmaker's shares traded at $19.01, down 17 cents and near a ten-year low. Wall Street remains unconvinced that Pfizer will be able to generate enough sales to keep growth going when cholesterol blockbuster Lipitor faces generic competitors as early as 2010, and Lyrica has been one of the company's main answers to bring in sales. In addition, Lyrica closely resembles Neurontin, another Pfizer drug used for epilepsy that would be grouped under the FDA's new label.
Pfizer officials say they have been trying to get a meeting with the agency since late January when the FDA unexpectedly said it had noted a link between the drugs and an increased risk of suicide.
Abbott Laboratories, whose sales of its Depakote epilepsy pill passed $1.2 billion last year, said its review of clinical trial data "shows no incremental risk of suicide-related events with Depakote." However, the company said it will work with the FDA to implement any label changes it recommends.
Some epilepsy researchers worry that the FDA is responding to pressure from Congress and public-interest groups because of a series of embarrassing drug problems in recent years.
"I think the FDA is overreacting," said Ilo Leppik of the University of Minnesota. Dr. Leppik, who has researched epilepsy treatments for 35 years, added, "This came out of the blue" this year. He said he believes the FDA is acting quickly to label the epilepsy drugs because of the agency's late response in 2004 to concerns that popular antidepressants were linked to suicide among teenagers.
In October 2004, the FDA required manufacturers of all antidepressants to add a "black box" warning about links to an increased risk of suicidal thinking and behavior in children and adolescents.
The FDA is now doing "early warnings" of potential side-effect signals in the epilepsy drugs said FDA spokeswoman Julie Zawisza. Earlier this year, the agency issued an early warning for suicidality about the popular allergy medicine Singulair.
Epilepsy patients are already at increased risk for suicide and depression. Dr. Frank Gilliam, an epilepsy specialist at Columbia University said many studies have demonstrated this connection and one key investigation suggested that nearly 10% of epilepsy patients suffer severe depression.
"When the base rate is 9%, it's hard for me to see the importance of overemphasizing the .2% difference" between placebo-takers and epilepsy drug users, Dr. Gilliam said.
--Shirley Wang contributed to this article.
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