The multinational drug company Eli Lilly faces the threat of lawsuits from US state governments over alleged illegal practices in the marketing of its drug olanzapine (Zyprexa), which is used to treat schizophrenia and bipolar disorder.
The company has already agreed to settle more than 18 000 outstanding product liability claims that relate to the drug in the United States for an undisclosed sum.
Last week, the attorney generals of Vermont and Illinois issued civil investigative demands, equivalent to subpoenas, ordering the company to hand over internal documents relating to the marketing of olanzapine. The states are investigating claims that the company concealed data that show serious risk of side effects including weight gain, hyperglycaemia, and diabetes
Investigators are also looking at whether Eli Lilly illegally promoted the off-label use of the drug to doctors. Although US doctors are free to prescribe drugs off-label, drug companies are barred from marketing drugs for any purpose not approved by the Food and Drugs Administration.
Both Florida and California may seek to recover money spent on olanzapine by their Medicaid programmes. Florida's attorney general already subpoenaed some olanzapine marketing data in 2005. Eli Lilly is refusing to discuss the details of cases but says it is cooperating with all state investigations and with a federal government investigation that began in 2005.
The sums involved could be substantial because olanzapine has been Eli Lilly's best overall seller since its introduction in 1996, with total sales of more than $30bn (£15bn; €23bn). More than 20 million patients have taken the drug. Olanzapine was the largest single drug expenditure of California's Medi-Cal programme in 2005, costing almost $250m.
To date, Eli Lilly has agreed to pay $700m in a master settlement with 8000 claimants reached in 2005. The company has also settled roughly 2500 more cases individually for undisclosed sums. Three weeks ago, it announced settlements in a further 18 000 cases, for a sum the company described as “not expected to exceed $500 million.”
These settlements included some state and federal product liability suits, but the company says it will “continue to vigorously defend Zyprexa in the remaining product liability cases, third-party payer and state cases.”
Documents submitted by the company at a plaintiff's request in one case have already been publicised by the New York Times, after they were passed on to the newspaper by James Gottstein, a lawyer in Alaska. They relate to the successful Viva Zyprexa publicity campaign of 1999-2002.
The documents apparently suggest that Eli Lilly failed to disclose company data showing that 16% of people taking olanzapine for a year gained more than 30 kg, according to the New York Times (www.nytimes.com, 21 Dec 2006, “Eli Lilly said to play down risk of top pill”).
The New York Times also described an internal memo noting that “dementia should be first message” to family doctors, since these physicians did not generally treat schizophrenia or bipolar disorder, the drug's approved indications. Olanzapine now carries an FDA warning that it can increase risk of death in patients with dementia.
Eli Lilly won a court order last month asserting the confidentiality of the documents, and forcing Mr Gottstein and 15 other people to return their copies to the company, but the New York Times itself was not mentioned in the injunction and has said it will keep its copies (BMJ 2007;334:59).
A major US government review of the use of antipsychotic drugs found that off-label use is widespread and often not supported by the available evidence. The Agency for Healthcare Research and Quality report found that atypical antipsychotics such as olanzapine are often prescribed for unapproved conditions such as depression, dementia, and geriatric aggression despite serious side effects and little evidence of efficacy.
David Atkins, chief medical officer at the agency's Center for Outcomes and Evidence, said, “Atypical antipsychotics have a poorly understood mechanism of action. That's one reason, I suspect, why people are willing to think they may be helpful in a broad range of conditions.”