Widely advertised ‘restless legs’ drugs move into court

Susan Heylman, Associate Editor

The television advertisements for Mirapex show a stick figure, whose legs have annoying sensations that keep it up at night—sensations like “lightning legs,” “pins and needles,” “creepy crawlies,” and “the urge to move.” It’s restless legs syndrome, or RLS. Relief, however, is only a pill away, says the ad, which promises, “When your legs feel better, you feel better.”

Although many skeptics believe that restless legs syndrome is an imaginary disease created by pharmaceutical companies trying to sell more drugs to consumers, the syndrome is a real neurological disorder, according to the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. It is characterized by unpleasant sensations in the legs and an uncontrollable urge to move when at rest in an effort to relieve those feelings.

People with RLS have difficulty falling asleep and staying asleep. Some researchers estimate that RLS affects as many as 12 million Americans.

Mirapex (pramipexole), manufactured by Germany-based Boehringer Ingelheim Pharmaceuticals and Pfizer, Inc., is a dopamine agonist that was first approved by the FDA for the treatment of Parkinson’s disease in 1997, along with GlaxoSmithKline’s similar drug Requip (ropinirole). After researchers discovered that dopamine agonists also reduced the symptoms of restless legs, the manufacturers obtained FDA approval of Mirapex and Requip for the treatment of moderate to severe RLS in 2005.

Both products, however, have caused serious side effects in Parkinson’s patients, including uncontrolled behaviors such as pathological gambling, hypersexuality, and compulsive eating and shopping. Many patients who have experienced these behaviors after using the drugs have filed products liability suits against the manufacturers, and lawyers are exploring potential litigation based on the same adverse effects in RLS patients.

Several hundred Mirapex cases are pending in multidistrict litigation (MDL) in Minnesota against Boehringer, Pfizer, Pharmacia, and Upjohn—the companies that developed, manufacture, and market Mirapex. Tara Sutton of Minneapolis, lead trial counsel in the MDL, said the plaintiffs are Parkinson’s disease patients who engaged in uncontrolled compulsive gambling. Others reported going on shopping sprees and overeating.

In the suit, the plaintiffs allege that the defendants knew Mirapex caused pathological gambling as early as November 2004 but withheld this information from the FDA, doctors, and the public, and that the companies falsely denied any link between Mirapex and gambling. Sutton anticipates that trials in three bellwether cases in the MDL will begin this July. (In re Mirapex Prods. Liab. Litig., No. 07-1836 (D. Minn. Nov. 27, 2007).)

Requip has also been the subject of lawsuits filed by patients who say that the manufacturer failed to warn them that the drug could cause compulsive behavior. In one case, a retired Texas doctor with Parkinson’s disease is suing Glaxo after losing more than $12 million gambling at six Las Vegas casinos while taking Requip. (Wells v. SmithKline Beecham Corp., No. A-06-CA-126-LY (W.D. Tex. filed Feb. 27, 2006).)

Although no RLS patients had filed cases at press time, consumer advocates and attorneys say such suits are likely, given the extensive advertising of Mirapex and Requip for restless legs syndrome. Before marketing their Parkinson’s drugs for the treatment of RLS, the manufacturers had to raise awareness about the syndrome because it was not well known to doctors or consumers. Stories in the media and direct-to-consumer (DTC) advertising helped the manufacturers make the case that RLS could be treated with the dopamine agonist class of drugs.

Since TV and print ads began appearing in 2005, sales of both Mirapex and Requip have increased. Glaxo, for example, reported that sales of Requip for the year ending December 31, 2006, grew 74 percent.

Consumer groups have raised concerns that the direct-to-consumer marketing campaign for RLS drugs, like many similar campaigns, has prompted consumers to seek unnecessary medical treatments that may have adverse side effects.

“Disease mongering” is a term coined by some drug-marketing critics to describe what they view as an effort by pharmaceutical companies to enlarge the market for a drug treatment by convincing people that they are suffering from something that can be medically treated. The pharmaceutical companies can do this either by narrowing the definition of what’s healthy or by expanding the definition of disease—and then creating campaigns to raise awareness of the ostensibly underdiagnosed and undertreated problem. By promoting a view of a particular condition as widespread, serious, and treatable, these campaigns help to expand markets for a new pharmaceutical product.

Consumer Reports has identified RLS advertising as an example of this practice. It recently analyzed a Requip television ad on its Health Blog’s ADWATCH feature. After asking, “Do you have restless legs, or have you just seen too many TV ads?” the consumer organization concluded: “While medications may provide welcome relief to some RLS patients, the ads could leave anyone who ever suffered fidgetiness when trying to go to sleep to wonder whether he or she has RLS and should seek treatment.”

Direct-to-consumer advertising has skyrocketed in the decade since the FDA changed its policy in 1997 to allow advertising of prescription drugs on television. Total real spending by pharmaceutical companies on drug promotion to professionals and consumers increased from $11.4 billion in 1996 to $29.9 billion in 2005. Of that, direct-to-consumer spending increased from $985 million in 1996 to $4.2 billion in 2005. (Julie M. Donohue et al., A Decade of Direct-to-Consumer Advertising of Prescription Drugs, 357 New Eng. J. Med. 673 (2007).)

Moreover, most DTC advertising campaigns are for new drugs used to treat chronic conditions. Of 20 drugs with the highest spending on ad campaigns, 17 of the campaigns began within a year after the FDA approved the drug. Peter Lurie, deputy director of the Washington, D.C.-based Public Citizen Health Research Group, said such advertising encourages people to use newer medications, which exposes them to drugs with weaker safety records and drives up the costs of health care.

Although the Institute of Medicine has called for the FDA to ban DTC advertising of new drugs, the agency has not done so. A moratorium on drug ads was proposed in the Food and Drug Administration Amendments Act of 2007, but that provision was dropped from the enacted version of the bill, in light of questions about the constitutionality of a moratorium.

The law does include new language about DTC ads, requiring that they have statements about risks and benefits that are “clear, conspicuous, and neutral.” The act also gives the FDA discretion to delay television ads while the agency performs its review to determine if changes to the ad are needed, but some lawyers have said that the provision probably will be challenged as an unconstitutional “prior restraint” of speech.

MDL action

Meanwhile, the Mirapex MDL is working its way through pretrial proceedings, with recent focus on the plaintiffs’ fraud-on-the-FDA claim and their demand for punitive damages.

In a November ruling, U.S. District Court Chief Judge James Rosenbaum found that the plaintiffs had asserted facts with sufficient particularity for their claim that the defendants had perpetrated fraud on the FDA. The judge cited the plaintiffs’ claim that Boehringer’s first Mirapex label deliberately downplayed a causal link with compulsive behaviors despite its awareness of the association. Rosenbaum also noted that the plaintiffs had cited specific public statements that Boehringer made denying any causal link. (In re Mirapex Prods. Liab. Litig., 2007 WL 4121662 (D. Minn. Nov. 9, 2007).)

Also in November, Magistrate Judge Franklin Noel issued a ruling that allowed some plaintiffs in the MDL’s lead cases to seek punitive damages, finding that the law of each plaintiff’s home state applies to his or her action. Under this ruling, plaintiffs from Louisiana and Massachusetts may not add a count for punitive damages because those states do not allow them in products liability actions, but plaintiffs from California, Georgia, New Jersey, Ohio, Pennsylvania, Texas, and Virginia may seek punitives.

Noel also concluded that plaintiffs from Florida, Minnesota, and Wisconsin had met their heightened pleading requirement by showing that the defendants had acted with disregard for the high probability of injury to others’ rights or safety. He cited the plaintiffs’ evidence showing that the defendants knew when they were bringing Mirapex to market that the drug could cause compulsive behaviors; that the companies failed to properly investigate the issue in their clinical trials; that once evidence emerged that Mirapex caused compulsive behaviors, they ignored it and then attempted to suppress it; and, rather than warning patients of the possible side effects of Mirapex, the defendants undertook misleading public relations campaigns, asserting that there was no relationship between Mirapex and compulsive behaviors. (In re Mirapex Prods. Liab. Litig., No. 07-1836 (D. Minn. Nov. 27, 2007).)

“The punitives count was a very significant hurdle that we were able to overcome,” said Sutton. “Now we’ll be able to put the issue in front of a jury.”

Send your comments and questions about the online version of TRIAL to us at trial@justice.org

News & trends February 2008 | Volume 44, Issue 2

Widely advertised ‘restless legs’ drugs move into court

Susan Heylman, Associate Editor

MDL action

News & trends
February 2008 | Volume 44, Issue 2