Lilly Denies Promoting Zyprexa for Off-Label Uses

NEW YORK, Dec. 20 -- In front-page news articles on successive days, the New York Times accused Lilly of a campaign to promote the off-label use of Zyprexa (olanzapine), its anti-psychotic medication, while systematically downplaying the drug's side effects. Lilly denied the allegations.

"At Lilly, we do not engage in off-label promotion, as alleged in the Times article," said Steven Paul, M.D., the company's executive vice-president for science and technology.

The newspaper, citing marketing documents obtained from a lawyer representing mentally ill patients, said the company had encouraged primary care physicians to prescribe Zyprexa for patients who did not have schizophrenia or bipolar disorder, the two conditions for which it is approved.

The newspaper also said the company had engaged in a decade-long effort to downplay the risk of weight gain and hyperglycemia associated with the drug, side effects that some critics suggest could lead to increased rates of type 2 diabetes.

Dr. Paul said the company had acted properly: "We believe that it is absolutely appropriate to discuss Zyprexa and its indicated uses with primary care physicians in the interest of meeting a critical medical need," he said in a statement posted on the company's Web site.

The statement added that Lilly "deplores the illegal release of select confidential documents."

The FDA, which is charged with enforcing the rule against marketing for off-label uses, did not respond to requests for comment on the newspaper's allegations.

The newspaper said the marketing documents outline a multi-year campaign -- dubbed "Viva Zyprexa" -- in which sales reps were to discuss representative case profiles with primary care physicians. But the case profiles included patients who would not ordinarily have been diagnosed with either schizophrenia or bipolar disease, the Times said.

Dr. Paul defended the company's appeal to primary care physicians. "About half of medical care for serious mental illness takes place in a primary care physician's office," he said, because many people either have no access to a psychiatrist or do not seek psychiatric care.

"Our experience in mental health has taught us that primary care physicians are asking for education on severe mental illnesses, since they see many of these patients in their offices," Dr. Stevens added.

The company said the documents given to the Times were a small fraction of 11 million documents that were originally part of a lawsuit in which patients taking Zyprexa claimed they developed diabetes as a result of taking the drug. Lilly agreed last year to pay million to settle about 8,000 of the claims, but more are before the courts.

The documents "do not represent an accurate view of company strategy or conduct," the company said.

Zyprexa, which accounted for more than billion in sales last year, is one of the most popular of the atypical antipsychotics, largely because it is seen to have fewer adverse effects than other medications, allowing patients to remain longer on the drug.

But two recent, large-scale comparative trials have suggested that older medications may do nearly as well and -- because they are less expensive -- may be more cost-effective.

Also, the class has been under attack because of its purported links to diabetes. The company acknowledges that some patients taking Zyprexa may experience weight gain, but has consistently held that there is no evidence showing it leads to type 2 diabetes.

Lilly is insisting on "a very high standard of evidence," according to Jeffery Lieberman, M.D., of Columbia, who led the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. It found that Zyprexa was the most effective of the newer anti-psychotic agents, although some of the older drugs were almost as good.

But, he said, the clinical community is all but convinced of the diabetes link. "From the standpoint of clinical experience and scientific evidence, there certainly seems to be an association with some of the anti-psychotic drugs and weight gain and metabolic effects, including the element of hyperglycemia," he said.

"This is something that I think is generally believed in the clinical community," he said. He noted that the FDA had required the company to add a warning about hyperglycemia to the drug's label.