More than one of seven prescriptions for common drugs are for off-label uses lacking scientific support. This practice is widespread, because when the FDA approves a drug for one use, doctors can prescribe it for whatever they want. While federal law makes it illegal for drug companies to promote drugs for non-approved uses, doctors have the right to prescribe what they consider the best treatment for their patients. This is where "off-label" use -- using a drug approved for one condition to treat another -- comes into practice.
A U.S. lawyer handling the lawsuits of mentally ill patients is alleging that Eli Lilly (NYSE:LLY) carried on a campaign to influence doctors to prescribe Zyprexa for off-label use, also referred to as "unapproved," "unlabeled," or "extra-label" use. Zyprexa is Lilly's best-selling product, with sales of $4.2 billion last year, accounting for nearly 30% of its overall revenue. About two million people take Zyprexa worldwide.
The New York Times broke the story, citing internal documents from Eli Lilly and email messages from its managers showing that the company has allegedly been promoting off-label use of its antipsychotic drug olanzapine (branded as Zyprexa) to treat dementia. Olanzapine is only approved by the FDA for the long-term treatment of schizophrenia, maintenance treatment of bipolar disorder, and treatment of certain types of acute episodes of bipolar disorder.
Additionally, documents show that Eli Lilly executives may have kept data from doctors about Zyprexa's tendencies to promote obesity and boost blood sugar, amid fears that information about the side effects could hurt sales of Lilly's best-selling product. Among patients taking Zyprexa, 30% gain 22 pounds or more after a year on the drug, and some patients have reported putting on more than 100 pounds, according to information published by Lilly.
In response to the New York Times story, Lilly claims that relevant facts about Zyprexa were not included in the article. Primarily, Lilly points to numerous studies in the last 10 years that the drug has been on the market, performed by Lilly, government agencies such as the National Institute of Mental Health, and others. These studies did not show a causal link between Zyprexa and diabetes.
Lilly contends that since Zyprexa was approved by the FDA in 1996, "the labeling provided to physicians identified the potentially clinically significant weight gain that was observed in more than half of all patients treated long-term with Zyprexa, as well as the diabetes-related adverse events observed in clinical trials." Lilly also mentions that the leaked documents are a tiny fraction of the more than 11 million pages of documents provided by Lilly as part of the litigation process; as such, the company says they do not accurately portray Lilly's conduct or strategy. There is even a suggestion that older patients who seem to have dementia may actually have schizophrenia. Others, however, feel that symptoms could not be confused with mild dementia, since schizophrenia is a severe disease that is almost always diagnosed when patients are in their teens or 20s.
In a multiyear promotional campaign that Lilly began in late 2000, Eli Lilly allegedly told its sales representatives to encourage primary care physicians to prescribe Zyprexa to older patients with symptoms of dementia. The documents show that Lilly encouraged primary care doctors to treat the symptoms and behaviors of schizophrenia and bipolar disorder, even if the doctors had not actually diagnosed those diseases. The company allegedly did so even though Lilly's own market research found that many primary care doctors did not consider themselves qualified to treat people with schizophrenia or severe bipolar disorder.
Zyprexa is not approved to treat dementia or dementia-related psychosis, and it even carries a warning from the FDA that it increases the risk of death in older patients with such ailments. However, the leaked documents mention that "dementia should be first message" of a campaign to primary doctors, and that some primary care doctors "might prescribe outside of label."
Federal laws bar drugmakers from promoting prescription drugs for off-label use, although doctors can prescribe drugs to any patient they wish. Despite such rules, data from a national survey in 2001 showed that an estimated 150 million prescriptions -- 21% of 160 common drugs -- were for off-label use, despite little or no evidence that the drug was effective for those uses.
Currently, several large drug companies are under either civil or criminal investigation for alleged efforts to expand the use of their drugs beyond the specific illness or condition for which they are approved. Lilly now faces federal and state investigations over its marketing of Zyprexa.
Companies can face large fines for promoting drugs for off-label treatments, but the FDA has limited ability to stop the practice. The first off-label case the Justice Department ever prosecuted involved Protropin, made by Genentech (NYSE:DNA). Although Protropin was approved for treating children with a growth hormone deficiency, the company was accused of promoting it for healthy short children. Genentech denied the charges, but paid $50 million to settle the case in 1999. In 2004, Pfizer (NYSE:PFE) agreed to pay more than $400 million to settle a case involving off-label promotion by a company it acquired. Johnson & Johnson (NYSE:JNJ) and Cephalon (NASDAQ:CEPH) have also been investigated for possible marketing violations connected to off-label uses.
Yet despite the prospect of large penalties, companies know that there is a lot of room to maneuver in the current rules. For example, drugmakers are barred from pitching doctors directly on unapproved uses of their drugs but, if a doctor or nurse asks a sales representative about it, those questions can be addressed. Companies can also sponsor continuing medical education (CME) sessions where off-label uses can be discussed.
The problem, of course, is that drug companies may push off-label uses of drugs harder than warranted, given the evidence. Even if they follow the rules and only hand out journal articles, the information may not tell the whole story, since the company doesn't have to distribute less favorable studies as well.
While some say the FDA should ban marketing of unapproved uses, the courts have so far ruled that companies have a constitutional right to hand out public information to doctors. This has given rise to a new strategy, which does not involve the FDA, of suits by consumer groups challenging drug company practices such as drug advertising. Citizen actions under state consumer laws have hit a number of drugmakers, including Pfizer.
In the short term, this will likely have little effect on Eli Lilly or other drug companies. The big pharmaceutical companies are often accused of misrepresenting the risks associated with their drugs or aggressively promoting the use of drugs. The litigation risk is probably not higher than would normally be seen with any drug company, so in the short-term, the effect should be neutral. Long-term, however, we will need to keep an eye on the FDA to see whether it clamps down on off-label marketing and prescribing.
In a nutshell, the debate hinges on preventing abuse of the promotion of off-label use while still making information about such use available to doctors. The FDA will have to consider the safety of patients, and public opinion will drive decisions to some extent. If the FDA takes an aggressive stance on off-label-use marketing, it could significantly shrink drug sales for companies whose revenues are derived largely from such off-label use.
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Fool contributor Stephen Albainy-Jenei is a patent attorney at Frost Brown Todd LLC, serving up chat at PatentBaristas.com. Feel free to write him with comments or questions. Stephen doesn't own shares of any company mentioned in this article. The Fool has a disclosure policy.
