Eli Lilly Documents Show Risks of Zyprexa were deliberately played down_NYT

Yesterday, we reported about a whistleblower's lawsuit against Johnson & Johnson
 to which the Texas Attorney General has joined forces. The issue is the marketing
of its antipsychotic drug, Risperdal. In a separate action,  Texas Comptroller filed a
complaint with the federal Inspector General about the exposure of the state's foster
children to these toxic drugs. See: http://www.ahrp.org/cms/content/view/411/29/

Today, a front page article in the New York Times by Alex Berenson, reports: 
"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."

Indeed, Lilly's internal documents provided by our colleague in Alaska,
James Gottstein, Esq. who heads PsychRights and represents psychiatric
patients who are coerced into taking drugs such as Zyprexa. Mr. Gottstein's
lawsuit against Alaska for its forced drugging of patients policy, won a
landmark decision requiring full disclosure of the drug's risks.

These documents (1995-2004) were obtained through a lawsuit against Lilly.
They provide evidence showing that the company knew–as early as 1999–about
the blood / sugar hazards of Zyprexa, and that the company concealed these
from doctors: In 1999, Dr. Alan Breier, then Lilly's chief scientist on Zyprexa, wrote: 
"Olanzapine-associated weight gain and possible hyperglycemia is a major threat
to the long-term success of this critically important molecule."

The Times reports that 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."

Like the Merck documents in Vioxx litigation, these internal Lilly documents
provide evidence of how the giants of this industry aggressively promote–even
lethal drugs.
Zyprexa showed a high risk of drug-induced diabetes early on, but 
the company sacrificed safety for profits.Zyprexa is Lilly's highest selling drug–
this $4.5 billion blockbuster poses severe risks of harm and early death:

"In 2000 and 2001, more warning signs emerged, the documents show. In four
surveys conducted by Lilly's 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."

In March 2002, Lilly rejected plans to give psychiatrists guidance about how
to treat diabetes, "worrying that doing so would tarnish Zyprexa's reputation."
The Times reports Lilly's internal memo states: "having our reps provide
[educational materials about] diabetes would further build its association to
Zyprexa."  At the same time the documents show that Lilly expanded its
market to primary care physicians who were completely unaware of the risk.
The Times reports that "Lilly sales material encouraged representatives to
promote Zyprexa as a "safe, gentle pshychotropic" suitable for people
with mild mental illness."

Not until 2004, did the FDA require Lilly and the other antipsychotic drugs
to carry warnings about diabetes-even though the risk for patients
prescribed Zyprexa is overwhelmingly greater than for patients on the other
drugs.  Lilly, clearly has influential "friends" at the FDA. The Times reports
that "a California doctor reported that 8 of his 35 patients on Zyprexa had
developed high blood sugar, including two who required hospitalization."

Lilly's documents confirm Robert Whitaker's assessment of the drug's safety
hazards–based on data submitted to the FDA. In Whitaker's ground breaking
book, Mad in America: Bad Science, Bad Medicine…, Perseus Press, 2001,
he reported: Of the 2,500 patients in pre-marketing clinical trials, two-thirds
dropped out; 20 died, 12 by suicide; 22% suffered serious adverse effects
and weight gain was on average 1 lb per week.  The Times reports that
30% of patients' health is undermined by drug-induced weight gain-some
have gained as much as 100lbs.

Those trial results led Dr. David Healy, in April, 2002, to conclude:  "The
studies in adults with Zyprexa that Lilly submitted to the FDA demonstrate,
as far as I can establish, a higher death rate on Zyprexa than on any other
anti-psychotic ever recorded.
In addition to this Lilly have suppressed data
on suicidal acts on Zyprexa from these trials. The data are not available in
the scientific literature, nor from FOI requests to the FDA, nor from
enquiries to the company. Despite this Lilly are engaged in trials with this
agent in children."  

See: Testing Psychotropic Drugs in Children, April 30, 2002 at http://www.ahrp.org/children/healy0402.php

Lilly's defense is posted on its website:
http://newsroom.lilly.com/ReleaseDetail.cfm?ReleaseID=222694
 
Lilly's effort to intimidate Jim Gottstein who obtained the documents for
use in a legal case-and who submitted them to the Times, are a demonstration
of the bullying tactics that Lilly uses: http://psychrights.org/index.htm
 
Lilly has continued its deceptive pattern of concealing from physicians
their products' serious risks of harm.  In 2005, the BMJ reported that Lilly
had made its Prozac-related documents inaccessible to independent analysts.
See: http://www.bmj.com/cgi/content/full/330/7481/7

Lilly bullied the BMJ to apologize for describing the Prozac documents as
"missing" when the more accurate description would be inaccessible. Until
those documents surfaced, Lilly denied, denied, denied the increased risk of
Prozac-induced suicidal behavior. The risk is now acknowledged on the label.
See discussion about what is contained in the Lilly Prozac documents:
http://www.ahrp.org/infomail/05/01/27.php

AHRP urges the States Attorney's General to collaborate on a criminal lawsuit
against the antipsychotic drug manufacturers for creating a health hazard by
concealing the serious risks of harm their drugs pose.

Contact: Vera Hassner Sharav
veracare@ahrp.org
 
~~~~~~~~~~~~~~~~~~~~~

http://www.nytimes.com/2006/12/17/business/17drug.html
THE NEW YORK TIMES
December 17, 2006
Eli Lilly Said to Play Down Risk of Top Pill
By ALEX BERENSON

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 Zyprexa's links to obesity and
its tendency to raise blood sugar -both known risk factors for diabetes.

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, which cover the period 1995 to 2004.

Zyprexa has become by far Lilly's 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 Zyprexa's 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.
"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." Hyperglycemia
is high blood sugar. 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.

And in that year and 2001, the documents show, Lilly's 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 Zyprexa's real-world use.

"In summary, there is no scientific evidence establishing that Zyprexa
causes diabetes," the company said. Lilly also said the documents should not
have been made public because they might "cause unwarranted fear among
patients that will cause them to stop taking their medication."

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 Zyprexa's importance
to Lilly's future and the need to keep concerns about diabetes and obesity
from hurting sales. But that effort became increasingly difficult as doctors
saw Zyprexa's 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 Zyprexa's
reputation. "Although M.D.'s like objective, educational materials, having
our reps provide some with diabetes would further build its association to
Zyprexa," 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 Zyprexa's side effects. Lilly sales
material encouraged representatives to promote Zyprexa as a "safe, gentle
psychotropic" 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 Lilly's assertion
that Zyprexa does not cause more cases of diabetes than other psychiatric
drugs. "When somebody gains weight, they need more insulin, they become more
insulin resistant," 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 & Johnson's Risperdal and AstraZeneca's
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."Patients should be told the truth about drugs
like Zyprexa," Mr. Gottstein said.

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 "illegal." 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
Vioxx's 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 patients' 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, Zyprexa's sales soared. But as
sales grew, reports rolled in to Lilly and drug regulators that the medicine
caused significant 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 hospitalization.

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 sales force should be told, "Don't introduce the issue!!!"
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 years.

In 2000 and 2001, more warning signs emerged, the documents show. In four
surveys conducted by Lilly's 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. Since then, Lilly
has acknowledged Zyprexa's effect on weight but has argued that it does not
necessarily correlate to diabetes. But Zyprexa's share of antipsychotic drug
prescriptions is falling, and some psychiatrists say they no longer believe
the information Lilly offers. "From my personal experience, at first my
concerns about weight gain with this drug were very significantly downplayed
by their field representatives," said Dr. James Phelps, a psychiatrist in
Corvallis, Ore. 'Their continued efforts to downplay that, I think in
retrospect, was an embarrassment to the company."

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. "I wind up using it as an emergency medicine, where it's superb,"
he said. "But I'm trying to get my patients off of Zyprexa, not put them on."

Copyright 2006 The New York Times Company

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