Eli Lilly risks our health to increase profits


Richard Moore

Original source URL:

December 17, 2006

Eli Lilly Said to Play Down Risk of Top Pill

The drug maker Eli Lilly has engaged in a decade-long effort to play down the 
health risks of Zyprexa, its best-selling medication for schizophrenia, 
according to hundreds of internal Lilly documents and e-mail messages among top 
company managers.

The documents, given to The Times by a lawyer representing mentally ill 
patients, show that Lilly executives kept important information from doctors 
about Zyprexa¹s links to obesity and its tendency to raise blood sugar ‹ both 
known risk factors for diabetes.

Lilly¹s 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 Zyprexa¹s 
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, which cover the period 1995 to 2004.

Zyprexa has become by far Lilly¹s best-selling product, with sales of $4.2 
billion last year, when about two million people worldwide took the drug.

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 Zyprexa¹s safety, and said the documents had been taken out of context.

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

³Olanzapine-associated weight gain and possible hyperglycemia is a major threat 
to the long-term success of this critically important molecule,² Dr. Alan Breier
wrote in a November 1999 e-mail message to two-dozen Lilly employees that 
announced the formation of an ³executive steering committee for 
olanzapine-associated weight changes and hyperglycemia.² Hyperglycemia is high 
blood sugar.

At the time Dr. Breier, who is now Lilly¹s 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 ³unless we 
come clean on this, it could get much more serious than we might anticipate,² 
according to an e-mail message from one Lilly manager to another.

And in that year and 2001, the documents show, Lilly¹s own marketing research 
found that psychiatrists were consistently saying that many more of their 
patients developed high blood sugar or diabetes while taking Zyprexa than other 
antipsychotic drugs.

The documents were collected as part of lawsuits on behalf of mentally ill 
patients against the company. Last year, Lilly agreed to pay $750 million to 
settle suits by 8,000 people who claimed they developed diabetes or other 
medical problems after taking Zyprexa. Thousands more suits against the company 
are pending.

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 Zyprexa¹s real-world use.

³In summary, there is no scientific evidence establishing that Zyprexa causes 
diabetes,² the company said.

Lilly also said the documents should not have been made public because they 
might ³cause unwarranted fear among patients that will cause them to stop taking
their medication.²

As did similar documents disclosed by the drug maker Merck last year in response
to lawsuits over its painkiller Vioxx, the Lilly documents offer an inside look 
at how a company marketed a drug while seeking to play down its side effects. 
Lilly, based in Indianapolis, is the sixth-largest American drug maker, with $14
billion in revenue last year.

The documents ‹ which include e-mail, marketing material, sales projections and 
scientific reports ‹ are replete with references to Zyprexa¹s importance to 
Lilly¹s future and the need to keep concerns about diabetes and obesity from 
hurting sales. But that effort became increasingly difficult as doctors saw 
Zyprexa¹s side effects, the documents show.

In 2002, for example, Lilly rejected plans to give psychiatrists guidance about 
how to treat diabetes, worrying that doing so would tarnish Zyprexa¹s 
reputation. ³Although M.D.¹s like objective, educational materials, having our 
reps provide some with diabetes would further build its association to Zyprexa,²
a Lilly manager wrote in a March 2002 e-mail message.

But Lilly did expand its marketing to primary care physicians, who its internal 
studies showed were less aware of Zyprexa¹s side effects. Lilly sales material 
encouraged representatives to promote Zyprexa as a ³safe, gentle psychotropic² 
suitable for people with mild mental illness.

Some top psychiatrists say that Zyprexa will continue to be widely used despite 
its side effects, because it works better than most other antipsychotic 
medicines in severely ill patients. But others say that Zyprexa appears no more 
effective overall than other medicines.

And some doctors who specialize in diabetes care dispute Lilly¹s assertion that 
Zyprexa does not cause more cases of diabetes than other psychiatric drugs. 
³When somebody gains weight, they need more insulin, they become more insulin 
resistant,² Dr. Joel Zonszein, the director of the clinical diabetes center at 
Montefiore Medical Center in the Bronx, said when asked about the drug.

In 2003, after reviewing data provided by Lilly and other drug makers, the 
F.D.A. said that the current class of antipsychotic drugs may cause high blood 
sugar. It did not specifically single out Zyprexa, nor did it say that the drugs
had been proven to cause diabetes.

The drugs are known as atypical antipsychotics and include Johnson & Johnson¹s 
Risperdal and AstraZeneca¹s Seroquel. When they were introduced in the 
mid-1990s, psychiatrists hoped they would relieve mental illness without the 
tremors and facial twitches associated with older drugs. But the new drugs have 
not proven significantly better and have their own side effects, said Dr. 
Jeffrey Lieberman, the lead investigator on a federally sponsored clinical trial
that compared Zyprexa and other new drugs with one older one.

The Zyprexa documents were provided to the Times by James B. Gottstein, a lawyer
who represents mentally ill patients and has sued the state of Alaska over its 
efforts to force patients to take psychiatric medicines against their will. Mr. 
Gottstein said the information in the documents raised public health issues.

³Patients should be told the truth about drugs like Zyprexa,² Mr. Gottstein 

Lilly originally provided the documents, under seal, to plaintiffs lawyers who 
sued the company claiming their clients developed diabetes from taking Zyprexa. 
Mr. Gottstein, who is not subject to the confidentiality agreement that covers 
the product liability suits, subpoenaed the documents in early December from a 
person involved in the suits.

In its statement, Lilly called the release of the documents ³illegal.² The 
company said it could not comment on specific documents because of the 
continuing product liability suits.

In some ways, the Zyprexa documents are reminiscent of those produced in 
litigation over Vioxx, which Merck stopped selling in 2004 after a clinical 
trial proved it caused heart problems. They treat very different conditions, but
Zyprexa and Vioxx are not entirely dissimilar. Both were thought to be safer 
than older and cheaper drugs, becoming bestsellers as a result, but turned out 
to have serious side effects.

After being pressed by doctors and regulators, Merck eventually did test Vioxx¹s
cardiovascular risks and withdrew the drug after finding that Vioxx increased 
heart attacks and strokes.

Lilly has never conducted a clinical trial to determine exactly how much Zyprexa
raises patients¹ diabetes risks. But scientists say conducting such a study 
would be exceedingly difficult, because diabetes takes years to develop, and it 
can be hard to keep mentally ill patients enrolled in a clinical trial.

When it was introduced, Zyprexa was the third and most heralded of the atypical 
antipsychotics. With psychiatrists eager for new treatments for schizophrenia, 
bipolar disorder, and dementia, Zyprexa¹s sales soared.

But as sales grew, reports rolled in to Lilly and drug regulators that the 
medicine caused massive weight gain in many patients and was associated with 
diabetes. For example, a California doctor reported that 8 of his 35 patients on
Zyprexa had developed high blood sugar, including two who required 

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, ³Don¹t introduce the issue!!!² 
Meanwhile, the company researched combinations of Zyprexa with several other 
drugs, hoping to alleviate the weight gain. But the combinations failed.

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 

In 2000 and 2001, more warning signs emerged, the documents show. In four 
surveys conducted by Lilly¹s marketing department, the company found that 70 
percent of psychiatrists polled had seen at least one of their patients develop 
high blood sugar or diabetes while taking Zyprexa, compared with about 20 
percent for Risperdal or Seroquel. Lilly never disclosed those findings.

By mid-2003, Lilly began to change its stance somewhat, publicly acknowledging 
that Zyprexa can cause severe obesity. Marketing documents make clear that by 
then Lilly believed it had no choice. On June 23, 2003, an internal committee 
reported that Zyprexa sales were ³below plan² and that doctors were 
³switching/avoiding Zyprexa.²

Since then, Lilly has acknowledged Zyprexa¹s effect on weight but has argued 
that it does not necessarily correlate to diabetes. But Zyprexa¹s share of 
antipsychotic drug prescriptions is falling, and some psychiatrists say they no 
longer believe the information Lilly offers.

³From my personal experience, at first my concerns about weight gain with this 
drug were very significantly downplayed by their field representatives,² said 
Dr. James Phelps, a psychiatrist in Corvallis, Or. ŒTheir continued efforts to 
downplay that, I think in retrospect, was an embarrassment to the company.²

Dr. Phelps says that he tries to avoid Zyprexa because of its side effects but 
sometimes still prescribes it, especially when patients are acutely psychotic 
and considering suicide, because it works faster than other medicines.

³I wind up using it as an emergency medicine, where it¹s superb,² he said. ³But 
I¹m trying to get my patients off of Zyprexa, not put them on.²

Copyright 2006 The New York Times Company

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