Lilly's Dubious Marketing of Zyprexa

The New York Times published articles yesterday and today about how Eli Lilly and Co. marketed its best-selling anti-psychotic drug, Zyprexa (olanzapine). The articles revealed several issues.

Lilly's Marketers Minimized the Risks of Obesity and Diabetes

In particular, (quotes from yesterday's article somewhat re-ordered):

Lilly’s own published data, which it told its sales representatives to play down in conversations with doctors, has shown that 30 percent of patients taking Zyprexa gain 22 pounds or more after a year on the drug, and some patients have reported gaining 100 pounds or more. But Lilly was concerned that Zyprexa’s sales would be hurt if the company was more forthright about the fact that the drug might cause unmanageable weight gain or diabetes, according to the documents [supplied to the Times], which cover the period 1995 to 2004.

Critics, including the American Diabetes Association, have argued that Zyprexa, introduced in 1996, is more likely to cause diabetes than other widely used schizophrenia drugs. Lilly has consistently denied such a link, and did so again on Friday in a written response to questions about the documents. The company defended Zyprexa’s safety, and said the documents had been taken out of context.

The documents show that Lilly encouraged its sales representatives to play down those effects when talking to doctors. In one 1998 presentation, for example, Lilly said its salespeople should be told, 'Don’t introduce the issue!!!'

To reassure doctors, Lilly also publicly said that when it followed up with patients who had taken Zyprexa in a clinical trial for three years, it found that weight gain appeared to plateau after about nine months. But the company did not discuss a far less reassuring finding in early 1999, disclosed in the documents, that blood sugar levels in the patients increased steadily for three years.

But as early as 1999, the documents show that Lilly worried that side effects from Zyprexa, whose chemical name is olanzapine, would hurt sales.

'Olanzapine-associated weight gain and possible hyperglycemia is a major threat to the long-term success of this critically important molecule, Dr. Alan Breier wrote in a November 1999 e-mail message to two-dozen Lilly employees that announced the formation of an 'executive steering committee for olanzapine-associated weight changes and hyperglycemia.'

At the time Dr. Breier, who is now Lilly’s chief medical officer, was the chief scientist on the Zyprexa program.

In 2000, a group of diabetes doctors that Lilly had retained to consider potential links between Zyprexa and diabetes warned the company that 'unless we come clean on this, it could get much more serious than we might anticipate,' according to an e-mail message from one Lilly manager to another.

Lilly did expand its marketing to primary care physicians, who its internal studies showed were less aware of Zyprexa’s side effects. Lilly sales material encouraged representatives to promote Zyprexa as a “safe, gentle psychotropic” suitable for people with mild mental illness.

Not surprisingly, Lilly spokespeople did not agree with the Times' assertions.

On Friday, in its written response, Lilly said that it believed that Zyprexa remained an important treatment for patients with schizophrenia and bipolar disorder. The company said it had given the Food and Drug Administration all its data from clinical trials and reports of adverse events, as it is legally required to do. Lilly also said it shared data from literature reviews and large studies of Zyprexa’s real-world use.

Lilly's Marketers Promoted Zyprexa for Unapproved Uses, Particularly Dementia
According to the second article,

Lilly encouraged primary care physicians to use Zyprexa, a powerful drug for schizophrenia and bipolar disorder, in patients who did not have either condition, according to internal Lilly marketing materials.

In the [promotional] campaign, called Viva Zyprexa, Lilly told its sales representatives to suggest that doctors prescribe Zyprexa to older patients with symptoms of dementia.

Zyprexa is not approved to treat dementia or dementia-related psychosis, and in fact carries a prominent warning from the F.D.A. that it increases the risk of death in older patients with dementia-related psychosis.

Yet in 1999 and 2000 Lilly considered ways to convince primary care doctors that they should use Zyprexa on their patients. In one document, an unnamed Lilly marketing executive wrote that these doctors 'do treat dementia' but 'do not treat bipolar; schizophrenia is handled by psychiatrists.'

As a result, 'dementia should be first message,' of a campaign to primary doctors, according to the document, which appears to be part of a larger marketing presentation but is not marked more specifically.

Later, the same document says that some primary care doctors 'might prescribe outside of label.'

As part of the 'Viva Zyprexa' campaign, in packets for its sales representatives, Eli Lilly created the profiles of patients whom it said would be suitable candidates for Zyprexa.

The third patient was 'Martha,' a widow with adult children 'who lives independently and has been your patient for some time.' Martha was described as being agitated and having disturbed sleep, but without the symptoms of paranoia or mania that typically marked a person with schizophrenia or bipolar disorder.

[Lilly spokeswoman] Ms. Nobles said that Lilly had actually intended Martha’s profile to represent a patient with schizophrenia. But psychiatrists outside the company said this claim defied credibility, especially given Martha’s age. Instead, she appeared to have mild dementia, they said.

This appears to be yet another sad tale of how marketing enthusiasm has been given free rein in the pharmaceutical industry, unopposed by any sense of the evidence of particular drugs' benefits and risks.

This is another reminder about how skeptically physicians ought to view the marketing of health care goods and services.

Note that several other health care bloggers have commented on this story (See Medrants, Retired Doctor's Thoughts, and Clinical Psychology and Psychiatry). But given the size of the company involved, and the popularity of the drug, it seems worthy of all this attention.