Playing Down the Risks of Zyprexa

Eli Lilly been concealing critical data concerning the risks of its drug Zypreza. With wide coverage in the New York Times and on the Internet, the drug marketer is now intimidating health care advocates, researchers, and the media in an effort to prevent disclosure and keep information from reaching physicians and the public.

[PsychRights.org](http://www.Psyc [The Court's decision (Feb. 13, hRights.org) 2007)](http://www.narpa.org/Memor - Updated regularly, with links andum%20Final%20Judgment%20Order% to all legal briefs and documents 20&%20Injunction%2007504.pdf) [Alliance for Human Research [Brief for Intervenors submitted Protection](http://www.ahrp.org/c by the Bazelon ms/component/option,com_frontpage Center](http://www.narpa.org/zypr /Itemid,1/) exa%20intervention%20motion.pdf) [Eli Lilly Targets Free Speech in [Alliance for Human Rights Battle Over Zyprexa Protection (AHRP) Documents](http://http://mindfree Brief](http://www.narpa.org/zypre dom.org/know/psych-drug-corp/eli- xa1.pdf) lilly-secrets/zyprexakills) (MindFreedom) [Eli Lilly lawyers email to suppress Zyprexa [Eli Lilly Motion to Intervene documents](http://mindfreedom.org and Quash /know/psych-drug-corp/eli-lilly-s Subpoena](ttp://psychrights.org/S ecrets/email-to-suppress) tates/Alaska/CaseXX/EilLilly/EliL illy-MtntoInterveneandQuash.pdf) [Brief of the Electronic Freedom Foundation](http://psychrights.or g/States/Alaska/CaseXX/EilLilly/E FF1-7-07Brief.pdf) filed January 9, 2007\ \ (See NY Times and other articles below) +++

March 8, 2008

Lilly Waited Too Long to Warn About Schizophrenia Drug, Doctor Testifies

By ALEX BERENSON [ANCHORAGE --- Eli Lilly, the drug maker, could and should have warned physicians as early as 1998 about the link between Zyprexa, its best-selling schizophrenia medicine, and diabetes, an expert witness told jurors Friday in a lawsuit that claims that Zyprexa has caused many mentally ill people to develop diabetes.

Instead, Lilly hid Zyprexa's risks from doctors to protect the drug's sales, according to the witness, Dr. John Gueriguian. Lilly waited until 2007 to add strong warnings to Zyprexa's label to reflect the drug's tendency to cause severe weight gain and blood sugar changes.

Lilly put “profit over concern of the consumer,” Dr. Gueriguian said Friday near the end of four hours of testimony.

Zyprexa, a drug for schizophrenia and bipolar disorder, is by far Lilly's top-selling product, with worldwide sales of $4.8 billion last year.

The company has said it did nothing wrong and fully disclosed what it knew about Zyprexa to the Food and Drug Administration.

Dr. Gueriguian is testifying on behalf of the State of Alaska, which has sued Lilly to recover its costs for treating Medicaid patients who developed diabetes after taking Zyprexa. The trial is being heard in state court in downtown Anchorage before a jury of seven women and five men.

Dr. Gueriguian is a specialist on diabetes and was a medical reviewer for the Food and Drug Administration for 20 years before retiring in 1998.

At the F.D.A., he recommended against the approval of Rezulin, a diabetes drug that was later withdrawn for causing severe liver damage in patients.

Under examination by Tommy Fibich, a lawyer from Houston who is representing Alaska, Dr. Gueriguian methodically reviewed about a dozen documents in which Lilly scientists and executives discussed the potential links between Zyprexa and diabetes.

Zyprexa was introduced in September 1996 and hailed as a breakthrough medicine for the treatment of schizophrenia.

But doctors quickly began to report to Lilly that patients suffered severe weight gain, high blood sugar and even diabetes after taking the drug.

By the fall of 1998, the combination of adverse-event reports, clinical trial data that showed hyperglycemia and weight gain, and problems in animal studies should have been enough for Lilly to warn doctors about Zyprexa's links to diabetes, Dr. Gueriguian said. Instead, the company did nothing.

Documents from 1999 and 2000 also showed that Lilly was accumulating evidence of Zyprexa's risks but not sharing it with doctors, he testified.

And in 2002, only 10 months after Lilly began selling Zyprexa in Japan, medical regulators in that country required Lilly to warn doctors against using Zyprexa in diabetic patients.

But Lilly did not issue a similar advisory to doctors in the United States. Instead, the company advised its sales representatives not to discuss diabetes with doctors unless the doctors brought it up first, according to another document presented at the trial.

“We will NOT proactively address the diabetes concerns,” the document, an internal Lilly memorandum, said.

Court recessed on Friday before lawyers for Lilly could cross-examine Dr. Gueriguian. They will have the opportunity to do so on Monday.

A lawyer for Lilly said after Dr. Gueriguian's testimony that the company had shared all it knew with the F.D.A. and that the question of the link between Zyprexa and diabetes was still a subject of scientific debate.

The Truth Is Not Free

Tuesday, September 11th, 2007

By David Egilman September 11, 2007

All that is needed for the forces of evil to succeed is for enough good people to remain silent.-- Edmund Bujrke

The consequences of silence can be devastating. My father spent WWII in a German concentration camp largely as a consequence of silence. In response to the Holocaust, which was facilitated by the silence of a nation, I have devoted much of my professional career to studying and reporting the effects of silence on public health.

Last December, I was subpoenaed for copies of internal documents that I acquired as a consulting witness in litigation against the pharmaceutical company Eli Lilly. I released all of the documents I had, which made their way to The New York Times and became the basis for four major articles. After the Times stories ran, 30 states subpoenaed documents detailing Lilly's sales, marketing and promotional practices for Zyprexa as part of civil investigations under state consumer protection laws.

I recently reached a settlement with Lilly and agreed to pay the company $100,000. I admitted responsibility for violating the protective order that kept Lilly's documents secret. I admitted that the documents I leaked did not tell the full story about Zyprexa. I did not, however, admit that Lilly's “story” of the drug is based on fact, nor did I admit to any illegal conduct. And notably, although Lilly claims that the stories that ran in the Times did not accurately reflect its marketing practices or its knowledge of Zyprexa's side effects, Lilly has refused to release documents that it claims paint a different picture. Even today, Lilly fights in court to keep those documents secret from the public.

However, I refuse to silence my voice on the dangerous effects of corporate secrecy. History has demonstrated time and time again that such silence brings nothing but harm.

The silence of asbestos companies and their doctors, who hid their knowledge of the hazards of asbestos, permitted a carcinogen to be used for a century in schools, homes and offices. The entire town of Libby, Montana fell victim to that silence. Too late, litigation revealed what companies and their doctors had known for over a hundred years. Asbestos was killing thousands.

The silence of flavoring companies and their doctors, who hid their knowledge of the hazards of butter flavored popcorn, allowed these toxic foods to be sold to an unsuspecting public for more than 20 years. The recent outbreak of lung disease in consumers of butter flavored popcorn is the cost of this silence. Yet litigation revealed the truth -- these companies had known the flavorings caused disease for decades. In this case, there may still be time to avoid another asbestos-like epidemic.

The silence of Eli Lilly & Company and their doctors about the hazards of Oraflex, a drug they knew caused fatal liver failure, resulted in unnecessary deaths of American patients. Once again, litigation revealed the truth. Lilly pleaded guilty to 25 criminal charges of failing to inform the United States government about adverse reactions to Oraflex and mislabeling the drug.

The same story keeps repeating itself. Over the years, silica, lead, tobacco, pesticides, beryllium, Vioxx, Oraflex and hundreds of other toxic products have ended up in our food, our medicine, our air and our water. It is the silence of corporations and their doctors, not a lack of knowledge, which is the root cause of this never-ending circle of public health disasters.

This blanket of silence is becoming so heavy that doctors are forgetting where their loyalties lie. The medical director of one asbestos company was asked why he hadn't warned his patients, those who developed asbestosis and cancer from their work, of the hazards of asbestos. He explained that he had indeed warned his patients; that the company was his “patient.” I refuse to go the way of that doctor and remain silent on issues important to the public health, for the cost is always the loss of innocent lives.

When I graduated from medical school, I took an oath to protect the public health. That oath supersedes all other agreements, including those that prevent me from protecting public health by releasing information. My obligation to the health and safety of others is the same as that of a physician who informs the police about a patient who has “in confidence” threatened injury on another. My obligation is the same as that of a pediatrician who “violates” confidentiality to report possible child abuse to the police.

If Lilly has “secret” documents that indicate that its drugs are safe or that their marketing practices were appropriate, they have the right to release them and it is in their interest to do so. Their silence is deafening.

Silence can injure and kill. For public health, the sound of silence is the funeral dirge. I have not and will never play that tune.

All that is needed for the forces of evil to succeed is for enough good people to remain silent.

\ David S. Egilman, MD, MPH is Clinical Associate Professor at Brown University's Department of Community Health.

The Pump Handle

From the New York Times:

December 19, 2006

Playing Down the Risks of a Drug

It was bad enough when studies showed that the newest and most heavily promoted drugs for treating schizophrenia weren't worth their high cost. Now the disturbing tale of their excessive use has taken a tawdry turn with revelations that Eli Lilly, a pharmaceutical giant, has consistently played down the risks of its best-selling antipsychotic drug, Zyprexa, and has promoted it for unapproved uses.

The details were spelled out in The Times this week by Alex Berenson, who drew on hundreds of internal Lilly documents that have surfaced in legal proceedings. Although Lilly says the documents present an inaccurate picture, they offer persuasive evidence that the company engaged in questionable behavior to prop up its best-selling drug, which creates almost 30 percent of Lilly's revenue.

Zyprexa belongs to a class of drugs that were billed as a significant advance over the first generation of antipsychotic drugs but turned out to have serious flaws. Zyprexa, for example, has a tendency to raise blood sugar and to promote obesity, both of which are risk factors for diabetes. Some 30 percent of the patients taking Zyprexa gain 22 pounds or more after a year on the drug, with some gaining 100 pounds or more. Yet the documents show that Lilly encouraged its sales representatives to play down these adverse effects when talking to doctors.

The documents also show that Lilly encouraged primary care physicians -- far less sophisticated than psychiatrists in treating mental illness -- to prescribe the drug for older patients with symptoms of dementia even though it was approved only for schizophrenia and bipolar disorder. It is illegal for companies to promote drugs for unapproved uses, but nearly every major drug company is under civil or criminal investigation for alleged efforts to do so.

Lilly contends that it has never promoted Zyprexa for unapproved uses and has always shown its marketing materials to the Food and Drug Administration, as required by law. Both claims ought to be tested in Congressional hearings that should focus on how well the industry complies with existing laws and how effectively the F.D.A. regulates the industry's marketing materials.

December 21, 2006

Disparity Emerges in Lilly Data on Schizophrenia Drug

By ALEX BERENSON

For at least a year, Eli Lilly provided information to doctors about the blood-sugar risks of its drug Zyprexa that did not match data that the company circulated internally when it first reviewed its clinical trial results, according to company documents.

The original results showed that patients on Zyprexa, Lilly's pill for schizophrenia, were 3.5 times as likely to experience high blood sugar levels as those taking a placebo, according to a February 2000 memo sent to top Lilly scientists. The memo is one of hundreds of internal Lilly documents provided to The New York Times by a lawyer in Alaska who represents mentally ill patients.

But the results that Lilly eventually provided to doctors until at least late 2001 were very different. Those results indicated that patients taking Zyprexa were only slightly more likely to suffer high blood sugar as those taking a placebo, or an inactive pill.

Another Lilly report, from November 1999, shows that Lilly found after examining 70 clinical trials that 16 percent of patients taking Zyprexa for a year gained more than 66 pounds.

The company did not publicly disclose that figure, instead focusing on data from a smaller group of clinical trials that showed about 30 percent of patients gained 22 pounds.

Weight gain and high blood sugar are important risk factors for diabetes, and the question of whether Zyprexa causes diabetes has been a subject of scientific debate for several years.

Lilly says no link has ever been proven.

In response to questions about the difference between its first view of the data and its subsequent public description, Lilly issued a statement yesterday saying that the later figures were accurate and the information in February 2000 was out of context.

In yesterday's statement, the company said that after the February 2000 memo, it re-examined its clinical trial results and found errors in its “final, standard quality check of the data.”

But the February 2000 document, which is labeled “Confidential,” does not indicate that the figures it contains are preliminary. In fact, in a footnote, it explains that the data exclude patients “from whom there was a probable lab error.”

A separate document from November 1999 includes handwritten figures identical to those from the February document, with additional detail about the increases in blood sugar that patients suffered.

The revised figures were shared with the Food and Drug Administration, Lilly said. It did not say whether it had ever disclosed the initial data to the F.D.A.

The F.D.A. did not respond to requests for comment yesterday.

The 2000 memo indicates that it was prepared as Lilly considered changing Zyprexa's prescription label to provide doctors with more information about the drug's potential to raise blood-sugar levels.

The issue was crucially important to the sales prospects of Zyprexa, which was introduced in 1996. Psychiatrists were already increasingly aware by 2000 that Zyprexa caused severe weight gain in many patients.

“In 1999, we already were thinking this drug causes weight gain --- that's clear --- and there could be a lot of other metabolic consequences of that,” Dr. David N. Osser, a psychiatry professor at Harvard University, said yesterday. “The weight gain itself is a known risk factor for diabetes.”

The February 2000 memo was prepared as background for a meeting of Lilly scientists to the possible changes for Zyprexa's label.

According to the memo, Lilly scientists initially wanted to propose a relatively straightforward statement on the label that high blood sugar had been observed in patients taking Zyprexa in clinical trials. That change was never made.

Lilly's analysis in early 2000 came at a time when some doctors and regulatory agencies were beginning to question whether Zyprexa could cause increases in blood sugar or diabetes. Although Lilly says that no link between Zyprexa and diabetes has ever been proven, the American Diabetes Association found in 2004 that Zyprexa was more likely to cause diabetes than other, similar drugs.

Zyprexa is by far Lilly's best-selling product, with $4.2 billion in sales in 2005, which represented 30 percent of Lilly's overall revenue. Zyprexa's active ingredient is a potent chemical that binds to receptors in the brain to reduce the hallucinations and delusions associated with schizophrenia and acute bipolar disorder. About two million people worldwide took Zyprexa last year.

At the February 2000 meeting for which the memo was prepared, the agenda was to discuss Zyprexa's tendency to cause high blood sugar, which is medically known as hyperglycemia.

According to the memo, Lilly had reviewed data from its clinical trials and found that “the incidence of treatment-emergent hyperglycemia in olanzapine group (3.6%) was higher than that in the placebo group (1.05%).” Olanzapine is the generic name for Zyprexa.

But when Lilly subsequently discussed the clinical trial results with doctors, it used a different comparison. Lilly told doctors that Zyprexa had caused 3.1 percent of patients --- not 3.6 percent --- to have high-blood sugar. And it said that 2.5 percent of patients on the placebo --- not 1.05 percent --- had high-blood sugar. As a result, the rates of high blood sugar in the two groups seemed almost identical in the revised data.

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 bkillion 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 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 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 salespeople 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. On June 23, 2003, an internal committee reported that Zyprexa sales were "below plan" and that doctors were "switching/avoiding Zyprexa."

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, Or. '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."\

December 18, 2006\ Drug Files Show Maker Promoted Unapproved Use\ By ALEX BERENSON

Eli 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.

The marketing documents, given to The New York Times by a lawyer representing mentally ill patients, detail a multiyear promotional campaign that Lilly began in Orlando, Fla., in late 2000. In the campaign, called Viva Zyprexa, Lilly told its sales representatives to suggest that doctors prescribe Zyprexa to older patients with symptoms of dementia.

A Lilly executive said that she could not comment on specific documents but that the company had never promoted Zyprexa for off-label uses and that it always showed the marketing materials used by its sales representatives to the Food and Drug Administration, as required by law.

“We have extensive training for sales reps to assure that they provide information to the doctors that's within the scope of the prescribing information approved by the F.D.A.,” Anne Nobles, Lilly's vice president for corporate affairs, said in an interview yesterday.

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. Federal laws bar drug makers from promoting prescription drugs for conditions for which they have not been approved --- a practice known as off-label prescription --- although doctors can prescribe drugs to any patient they wish.

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.”

Ms. Nobles said that the company had never promoted its drug for any conditions except schizophrenia and bipolar disorder. Older patients who seem to have dementia may actually have schizophrenia that has gone untreated, Ms. Nobles said.

Several psychiatrists outside the company said yesterday that they strongly disagreed with Lilly's claim. Schizophrenia is a severe disease that is almost always diagnosed when patients are in their teens or 20s. Its symptoms could not be confused with mild dementia, these doctors said.

Zyprexa is by far Lilly's best-selling product, with $4.2 billion in sales in 2005, 30 percent of its overall revenues. About two million people worldwide received it last year. Based in Indianapolis, Lilly is the sixth-largest American drug company.

The issue of off-label marketing is controversial in the drug industry. Nearly every company is under either civil or criminal investigation for alleged efforts to expand the use of its drugs beyond the specific illness or condition for which they are approved.

Lilly faces federal and state investigations over its marketing of Zyprexa. In its annual report for 2005, Lilly said that it faced an investigation by federal prosecutors in Pennsylvania and that the Florida attorney general's office had subpoenaed the company “seeking production of documents relating to sales of Zyprexa and our marketing and promotional practices with respect to Zyprexa.”

Since Lilly introduced Zyprexa in 1996, about 20 million patients worldwide have received the drug, which helps control the hallucinations and delusions associated with schizophrenia and severe mania. But Zyprexa also causes weight gain in many patients, and the American Diabetes Association found in 2004 that Zyprexa was more likely to cause diabetes than other widely used drugs for schizophrenia.

Lilly says that no link between Zyprexa and diabetes has been proven.

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. Representatives were told to discuss the patient profiles with doctors. One of the patients was a woman in her 20s who showed mild symptoms of schizophrenia, while another was a man in his 40s who appeared to have bipolar disorder.

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.

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.

“It'd be very unusual for this to be a schizophrenic patient,” said Dr. John March, chief of child and adolescent psychiatry at Duke University medical center. “Schizophrenia is a disease of teenagers and young adults.” Dr. March serves on Lilly's scientific advisory board.

Diagnostic criteria for schizophrenia include delusions, hallucinations, disorganized and incoherent speech, and grossly disorganized behavior. They also include so-called negative symptoms like social isolation and a flattening of the voice and facial expressions.

The documents also show that Lilly encouraged primary care doctors to treat the symptoms and behaviors of schizophrenia and bipolar disorder even if the doctors had not actually diagnosed those diseases in their patients. Lilly's market research had found that many primary care doctors did not consider themselves qualified to treat people with schizophrenia or severe bipolar disorder.

The campaign was successful, the documents show. By March 2001, about three months after the start of Viva Zyprexa, the campaign had led to 49,000 new prescriptions, according to a presentation that Michael Bandick, the brand manager for Zyprexa, gave at a national meeting of Lilly sales representatives in Dallas. Mr. Bandick did not say how many of those new prescriptions were for older patients with dementia.

Over all, sales of Zyprexa doubled between 1999 and 2002, rising from $1.5 billion to $3 billion in the United States. In 2002, the company changed the name of the primary care campaign to “Zyprexa Limitless” and began to focus on people with mild bipolar disorder who had previously been diagnosed as depressed --- even though Zyprexa has been approved only for the treatment of mania in bipolar disorder, not depression.

In a 2002 guide for representatives, Lilly presented the profile of “Donna,” a single mother in her mid-30s whose “chief complaint is, ‘I feel so anxious and irritable lately.' ” Several doctors' appointments earlier, she was “talkative, elated, and reported little need for sleep.”

Lilly's efforts to promote Zyprexa to primary care doctors disturbed some physicians, the documents show. In August 2001, a doctor in Virginia sent an e-mail message to Lilly and the F.D.A., complaining about a presentation from a Lilly sales representative who had discussed the hypothetical Martha with him.

The representative “presented an elderly female patient who was presented to her physician by her family complaining of insomnia, agitation, slight confusion, and had no physical finding to explain her state,” the doctor wrote. The representative then suggested that the doctor prescribe Zyprexa.

“I inquired what Zyprexa was indicated for she then indicated that many physicians might prescribe an antipsychotic for this patient. I then asked for her package insert and read to her that her product was indicated for schizophrenia and bipolar mania --- neither of which the presented patient had been diagnosed with,” the doctor wrote.

He added that he had never contacted the F.D.A. before but was “genuinely concerned about the promotion of this powerful drug to my peer community of primary care physicians outside of its approved and intended purpose.”

Tara Ryker, a spokeswoman for Lilly, said the company no longer uses “Martha” or “Donna” in its marketing. “We are constantly developing new promotional materials and new profiles,” she said.

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 yesterday that the information in the documents should be available to patients and doctors, as well as judges who oversee the hearings that are required before people can be forced to take psychiatric drugs.

“The courts should have this information before they order this stuff injected into people's unwilling bodies,” 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. Last year, Lilly agreed to pay $700 million to settle about 8,000 of the claims, but thousands more are pending. 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.

The “Viva Zyprexa” documents also provide color about Lilly's efforts to motivate its sales force as they marketed Zyprexa --- whose generic name is olanzapine --- to primary care doctors.

At the 2001 meeting in Dallas with Zyprexa sales representatives, Mr. Bandick praised 16 representatives by name for the number of prescriptions they had convinced doctors to write, according to a script prepared in advance of the meeting. More than 100 other representatives had convinced doctors to write at least 16 extra prescriptions and thus “maxed out on a pretty sweet incentive,” he said.

“Olanzapine is the molecule that keeps on giving,” Mr. Bandick said.

February 14, 2007

Judge Rules Drug Documents Must Be Returned to Eli Lilly

By LANDON THOMAS Jr.

A federal district judge in Brooklyn ruled yesterday that confidential marketing materials belonging to Eli Lilly & Company about its top-selling anti-psychotic drug Zyprexa must be returned to the company by a doctor and a lawyer who, the judge said, engaged in a scheme to leak them to the news media.

The documents were part of evidence provided by Lilly as part of a lawsuit filed by patients who claimed that side effects from Zyprexa caused excessive weight gain and diabetes.

In the 78-page decision, Judge Jack B. Weinstein of Federal District Court ordered Dr. David Egilman, a special expert for the plaintiffs, and James B. Gottstein, a lawyer in Alaska, to return the documents to Lilly.

A New York Times reporter, Alex Berenson, was given a copy of the documents, which showed that Lilly executives had kept information from doctors about Zyprexa's links to obesity and higher blood sugar, a claim Lilly has denied. He wrote front-page articles based on the information.

Eli Lilly has now paid $1.2 billion to settle more than 28,000 cases from individuals who contended that they developed diabetes or other diseases from taking Zyprexa.

In the ruling, Judge Weinstein said Mr. Berenson obtained the documents after he discussed with Dr. Egilman ways to circumvent a protective order. Mr. Berenson put Dr. Egilman in touch with Mr. Gottstein, the judge said, so that they might "employ a pretense to subpoena the documents." According to Judge Weinstein, the documents were sent to Mr. Gottstein via an expedited subpoena, which Lilly was unaware of. Mr. Gottstein then sent the papers to Mr. Berenson and others.

No other news organizations received the documents, the judge said, because Mr. Berenson told Mr. Gottstein that if the material was not delivered exclusively to him, the newspaper would not publish an article.

Mr. Berenson did not appear at an earlier hearing on the matter, where he was invited to testify. George Freeman, a lawyer for The New York Times Company, said that as a matter of "long-held principle," the company believed it would be "inappropriate for any of our journalists voluntarily to testify about newsgathering methods."

In a statement yesterday, Mr. Freeman said: "For the reasons set forth in our letter responding to Judge Weinstein's invitation, we declined to testify voluntarily about our newsgathering methods. Unfortunately, that resulted in an opinion which vastly overstates Alex's role in the release of the documents. We continue to believe that the articles we published were newsworthy and accurate, and we stand by them."

Mr. Gottstein, who is president and chief executive of the Law Project for Psychiatric Rights, said, "I was just trying to follow the law."

He said that a subpoena allowed him to adhere more closely to the protective order than if Dr. Egilman had given the documents directly to Mr. Berenson.

A spokeswoman for Eli Lilly, Marni Lemons, said: "Our adversaries carefully selected the documents to tell a story that they wanted to tell. These cherry-picked documents in no way reflect the strategies or activities of Eli Lilly & Company. Lilly feels vindicated because the judge issued an injunction that prohibits future wrongdoing by those who took the law into their own hands."

While the judge asked Mr. Gottstein and Dr. Egilman to return the documents, he did not ask Mr. Berenson to do so. Many of the documents are available on the Internet and the ruling does not ask that any newspaper or Web site take any action with regard to the papers.

Judge Weinstein reserved some harsh words for Mr. Berenson, whose conduct he called "reprehensible," and for The Times, pointing out that unlike the case of the Pentagon Papers, in which classified government documents were given to a Times reporter, "here a reporter was deeply involved in the effort to illegally obtain the documents."

The judge said that the documents' disclosure posed "significant risk of harm to Lilly," and that their "out of context" appearance in the news media might "lead to confusion in the patient community and undeserved reputational harm."

January 20, 2007\ States Study Marketing of Lilly Pill\ By ALEX BERENSON

Stepping up government investigations into Eli Lilly's marketing of its best-selling drug Zyprexa, state prosecutors in Illinois and Vermont have demanded that the company turn over information about the way it promoted the medication.

On Thursday, lawyers from the consumer protection division of the Illinois attorney general's office demanded that Lilly hand over marketing materials, e-mail messages, and other documents with information about promotion of Zyprexa. Vermont investigators issued a similar order yesterday morning.

The orders are the civil equivalents of criminal subpoenas, according to Deborah Hagan, the chief of the Illinois consumer protection division.

Illinois and Vermont are now part of a coordinated five-state civil investigation into the way Lilly promoted Zyprexa, a treatment for schizophrenia and bipolar disorder. The states are investigating whether Lilly tried to hide Zyprexa's risk of causing weight gain and other risks associated with diabetes and whether the company promoted Zyprexa for use in patients who do not have schizophrenia or bipolar disorder.

Federal laws prohibit such so-called “off label” marketing, although doctors may prescribe any drug for any disease that they believe the drug will help.

The orders on Thursday and yesterday are the first formal demands for Lilly documents from state attorneys and they indicate an escalation of the investigation, according to Ms. Hagan and Julie Brill, who is an assistant attorney general in Vermont.

“We can ask for documents; we can ask for answers to questions; and we can ask for people to come in and testify under oath,” Ms. Hagan said. Federal prosecutors in Philadelphia have also recently accelerated their own investigation into Lilly's marketing of Zyprexa.

In a statement yesterday, Lilly said it would cooperate with the investigations and had done nothing wrong. “We intend to cooperate with the Illinois attorney general's civil investigative demand relating to Zyprexa,” the company said. “We cannot comment further about this or other ongoing investigations.”

While the investigation being led by Illinois is civil, other investigations into Lilly's conduct are both civil and criminal. Attorneys general in California and Florida may seek to recover Medicaid payments that the states made for Zyprexa. Medicaid represents a sizable percentage of the drug's overall sales because many people who take the medicine are disabled and do not work.

Any fine or cost recovery could be sizable, because Zyprexa has been a commercial success. The drug is by far Eli Lilly's largest-selling product, with sales of $4.2 billion last year and about $30 billion since its introduction in 1996. More than 20 million people have taken Zyprexa since Lilly began selling the drug.

The investigations could continue for months or possibly years, people involved in the cases say, as investigators sift through tens of thousands of documents from the company and talk to current and former employees.

Zyprexa, whose generic name is olanzapine, is a potent chemical that binds with receptors in the brain to reduce the symptoms of schizophrenia and bipolar disorder. But Zyprexa also causes severe weight gain and changes in blood sugar and cholesterol in many patients who take it.

Internal Lilly documents provided to The New York Times last month by a lawyer in Alaska who represents people with mental illness indicate that Lilly has engaged in a decade-long campaign to play down the seriousness of the side effects of Zyprexa.

Lilly did not disclose to doctors that its own data showed that 16 percent of people taking Zyprexa for a year gained more than 66 pounds, according to the documents.

The documents also indicate that the company told its drug representatives to promote Zyprexa to doctors for the treatment of conditions other than bipolar disorder or schizophrenia.

Lilly has said it did not market Zyprexa off-label and said so again in its statement yesterday.

“Lilly is committed to the highest ethical standards and to promoting our medications only for approved uses,” the company said.

But its marketing materials have repeated references to promoting the drug for other uses. And some sales representatives and doctors have also said they believed that the company was marketing off-label.

Still, any criminal prosecution of the company could face a high burden. While settlements of off-label marketing cases have led to large fines, such cases so far have fizzled if they reach juries.

And as long as drug makers comply with federal requirements to provide data about their products to the Food and Drug Administration, companies have a relatively strong defense against criminal prosecution, according to lawyers who are experts in drug marketing.

The Register » Internet and Law »

Original URL: http://www.theregister.co.uk/2007/01/10/wiki_ordered_to_remove_link_to_drug_documents/

Wiki ordered to remove link to drug documents\ By OUT-LAW.COM\ Published Wednesday 10th January 2007 10:32 GMT

A wiki about a controversial prescription drug has been ordered by a US court to remove a link to documents which originated with Eli Lilly, the drug's manufacturer.

The drug, Zyprexa, has been the subject of payouts by Eli Lilly in cases over its alleged side effects. The pharmaceutical company still faces a large number of product liability lawsuits which claim that the schizophrenia and bipolar disorder treatment has caused patients to gain weight or to contract diabetes. Eli Lilly has already paid out $1.2bn to settle suits before they reached court, including $500m just last week.A wiki about the controversy, zyprexa.pbwiki.com, published a link to internal Eli Lilly documents which the New York Times said showed that the company deliberately downplayed the side effects of the drug, which are alleged to include weight gain, high blood sugar levels and diabetes.

The judge in one of the product liability cases, federal district Judge Jack Weinstein, ordered the site and a number of named individuals to refrain from distributing the documents or causing them to be distributed.

Digital rights group the Electronic Frontier Foundation (EFF) defended the free speech rights of one anonymous poster in front of Weinstein but the judge has reiterated his earlier decision. He will hear further arguments on 16th January.

The EFF argued that the ruling breached the individual's rights to free speech, enshrined in the first amendment of the US Constitution. The case is one of the first to involve citizen journalists and new online developments such as wikis in such a serious case.

"Preventing a citizen-journalist from posting links to important health information on a public wiki violates the first amendment," said EFF Senior Staff Attorney Fred von Lohmann. "Eli Lilly's efforts to censor these documents off the internet are particularly outrageous in light of the information reported by The New York Times, which suggests that doctors and patients who use Zyprexa need to know the information contained in those documents."

"The following individuals, entities and organisations who have received documents produced by Eli Lilly and Company are hereby enjoined from further disseminating these documents," said Weinstein's ruling. He goes on to name 13 individuals, at least four of them doctors, and four websites, including the Zyprexa wiki.

Wikis have exploded in popularity after the success of Wikipedia, the online encyclopaedia. A wiki is an online store of information which readers can amend, edit, expand and update. Conceived as collaborative tools, wikis gain their authority from the combined expertise of readers and activists rather than purely from the qualifications and expertise of a team of professional authors and editors.

OUT-LAW.COM is part of international law firm Pinsent Masons.

http://online.wsj.com/article/SB116792684556367193.html\ The Wall Street Journal\ Lilly Settles 18,000 Zyprexa Claims, but More Loom\ By AVERY JOHNSON\ January 5, 2007; Page A4

Eli Lilly & Co. moved to settle some 18,000 claims, most of which allege that it failed to adequately warn patients that its blockbuster antipsychotic Zyprexa can cause diabetes. But the drug maker must contend with some 1,200 holdouts and additional suits brought by insurers and state governments.

Lilly said it reached settlement agreements with 14 groups of law firms. The Indianapolis company said it would take a charge of under $500 million in the fourth quarter to settle the product-liability claims. In 2005, Lilly paid $700 million to compensate 10,500 claimants.\ The company said the cases -- settled or not -- were without merit. John Lechleiter, Lilly's president and chief operating officer, said the firm decided to settle because "it's in the best interest of Lilly, and physicians and patients."

The chairman of the plaintiffs' steering committee, Melvyn Weiss, said the settlement "reflects the judgment of some of the most outstanding tort lawyers in America that these are very difficult cases to try and that it was better to settle." He added, "Zyprexa is taken by people who are seriously ill with complicating diseases and trying these cases can be a daunting task, but I am confident there are cases that are triable."

Nonetheless, the legal troubles aren't over for Lilly and Zyprexa, still its bestseller in 2005 with $4.2 billion in revenue. The company faces suits brought by third-party payers contending, in large part, that they wouldn't have paid a premium for Zyprexa over other medicines if they had been adequately warned of its risks. And some lawyers say the remaining 1,200 personal-injury cases could still be a threat to the company.

State probes are intensifying. Connecticut Attorney General Richard Blumenthal, in concert with counterparts in other states, has expanded an investigation into Zyprexa's marketing practices and in an interview referred to a "potentially huge claim" alleging that the company promoted the drug to Medicaid and non-Medicaid patients for unapproved uses. California's attorney general mounted an investigation in September into the company's marketing of Zyprexa. Some attorneys general have filed suits seeking damages.

"What's left is a significant number of seriously injured plaintiffs'cases pending in state and federal court, and you have a half-dozen or more attorney-general cases and you have third-party payer class-action cases," said William Audet, the founding partner of Audet & Partners, a San Francisco firm representing more than 300 plaintiffs whose cases aren't part of the latest settlement.

Still, Lilly appears to be paying less to settle more cases in this round of legal agreements. The difference may be that Lilly changed Zyprexa's labeling in 2003 to reflect the increased diabetes risk, weakening later cases. Also, some lawyers said that second-round settlements tend to be smaller than the initial ones, since plaintiffs'lawyers tend to bring their strongest cases forward first. "The current settlement enables Lilly to postpone the disclosure of marketing information that shows its off-label promotion," said Thomas M. Sobol, a lawyer with the Cambridge, Mass., firm Hagens, Berman, Sobol & Shapiro, which brought suit on behalf of insurers.

A Lilly spokeswoman said the company will continue to try cases and that its rationale for settling wasn't to keep damaging information under seal.\ -- Peter Loftus and Heather Won Tesoriero contributed to this article.

Write to Avery Johnson at avery.johnson@WSJ.com1

December 27, 2006\ Ruling Upholds Eli Lilly's Patent on Drug

Eli Lilly & Company won a federal appeals court ruling on Tuesday upholding its patent on Zyprexa, the world's top-selling schizophrenia drug.

The United States Court of Appeals for the Federal Circuit, in Washington, affirmed a lower court decision that the patent was valid. The Ivax unit of Teva Pharmaceutical Industries and Dr. Reddy's Laboratories had claimed a federal judge was mistaken in ruling the drug was protected until Lilly's patent expires in 2011.

In addition, "Lilly did not fail to disclose information" to the patent office, as its rivals suggested, the judges said in their 21-page opinion. The opinion upheld a decision by Judge Richard L. Young of United States District Court in Indianapolis.

Lilly is also defending its marketing of Zyprexa in lawsuits filed by the attorneys general of Mississippi, Louisiana, West Virginia and Alaska alleging the company promoted the drug for unapproved uses and hid the risks of weight gain and diabetes.

Sales of Zyprexa dropped 16 percent and fell behind AstraZeneca's Seroquel as America's best-selling antipsychotic in 2005, according to IMS Health, which provides data on drug sales.

Worldwide sales of Zyprexa dropped 4.9 percent to $4.2 billion last year and accounted for about 29 percent of Lilly's revenue.

The drug has been Lilly's biggest seller since generic competition emerged to the antidepressant Prozac in 2001.

Stock in Lilly, which is based in Indianapolis, rose 43 cents in regular trading, to $51.78 a share.

Ivax and Dr. Reddy's, both of which have said their proposed alternatives to Zyprexa would infringe Lilly's patent, claimed the patent should not have been issued by the Patent and Trademark Office in 1993.

They asked the Washington-based court in April to rule the patent invalid.

THE NEW YORK TIMES\ January 4, 2007\ Mother Wonders if Psychosis Drug Helped Kill Son\ By ALEX BERENSON

At first, the psychiatric drug Zyprexa may have saved John Eric Kauffman's life, rescuing him from his hallucinations and other symptoms of acute psychosis. But while taking Zyprexa for five years, Mr. Kauffman, who had been a soccer player in high school and had maintained a normal weight into his mid-30s, gained about 80 pounds. He was found dead on March 27 at his apartment in Decatur, Ga., just outside Atlanta.

An autopsy showed that the 41-year-old Mr. Kauffman, who was 5 feet 10 inches, weighed 259 pounds when he died. His mother believes that the weight he gained while on Zyprexa contributed to the heart disease that killed him.

Eli Lilly, which makes Zyprexa, said in a statement that Mr. Kauffman had other medical conditions that could have led to his death and that “Zyprexa is a lifesaving drug.” The company said it was saddened by Mr. Kauffman's death.

No one would say Mr. Kauffman had an easy life. Like millions of other Americans, he suffered from bipolar disorder, a mental illness characterized by periods of depression and mania that can end with psychotic hallucinations and delusions. After his final breakdown, in 2000, a hospital in Georgia put Mr. Kauffman on Zyprexa, a powerful antipsychotic drug. Like other medicines Mr. Kauffman had taken, the Zyprexa stabilized his moods. For the next five and a half years, his illness remained relatively controlled. But his weight ballooned --- a common side effect of Zyprexa.

His mother, Millie Beik, provided information about Mr. Kauffman, including medical records, to The New York Times.

For many patients, the side effects of Zyprexa are severe. Connecting them to specific deaths can be difficult, because people with mental illness develop diabetes and heart disease more frequently than other adults. But in 2002, a statistical analysis conducted for Eli Lilly found that compared with an older antipsychotic drug, Haldol, patients taking Zyprexa would be significantly more likely to develop heart disease, based on the results of a clinical trial comparing the two drugs. Exactly how many people have died as a result of Zyprexa's side effects, and whether Lilly adequately disclosed those risks, are central issues in the thousands of product-liability lawsuits pending against the company, and in state and federal investigations.

Because Mr. Kauffman also smoked heavily for much of his life, and led a sedentary existence in his last years, no one can be sure that the weight he gained while on Zyprexa caused his heart attack.

Zyprexa, taken by about two million people worldwide last year, is approved to treat schizophrenia and bipolar disorder. Besides causing severe weight gain, it increases blood sugar and cholesterol in many people who take it, all risk factors for heart disease.\ In a statement responding to questions for this article, Lilly said it had reported the death of Mr. Kauffman to federal regulators, as it is legally required to do. The company said it could not comment on the specific causes of his death but noted that the report it submitted to regulators showed that he had “a complicated medical history that may have led to this unfortunate outcome.”\ “Zyprexa,” Lilly's statement said, “is a lifesaving drug and it has helped millions of people worldwide with schizophrenia and bipolar disorder regain control of their lives.”

Documents provided to The Times by a lawyer who represents mentally ill patients show that Eli Lilly, which makes Zyprexa, has sought for a decade to play down those side effects --- even though its own clinical trials show the drug causes 16 percent of the patients who take Zyprexa to gain more than 66 pounds after a year.

Eli Lilly now faces federal and state investigations about the way it marketed Zyprexa.\ Last week --- after articles in The Times about the Zyprexa documents --- Australian drug regulators ordered Lilly to provide more information about what it knew, and when, about Zyprexa's side effects.

Lilly says side effects from Zyprexa must be measured against the potentially devastating consequences of uncontrolled mental illness. But some leading psychiatrists say that because of its physical side effects Zyprexa should be used only by patients who are acutely psychotic and that patients should take other medicines for long-term treatment. “Lilly always downplayed the side effects,” said Dr. S. Nassir Ghaemi, a specialist on bipolar disorder at Emory University in Atlanta. “They've tended to admit weight gain, but in various ways they've minimized its relevance.”

Dr. Ghaemi said Lilly had also encouraged an overly positive view of its studies on the effectiveness of Zyprexa as a long-term treatment for bipolar disorder. There is more data to support the use of older and far cheaper drugs like lithium, he said.\ Last year, Lilly paid $700 million to settle 8,000 lawsuits from people who said they had developed diabetes or other diseases after taking Zyprexa. Thousands more suits are still pending.

But Ms. Beik is not suing Lilly. She simply wants her son's case to be known, she said, because she considers it a cautionary tale about Zyprexa's tendency to cause severe weight gain. “I don't think that price should be paid,” she said.

Mr. Kauffman's story, like that of many people with severe mental illness, is one of a slow and steady decline. Growing up in DeKalb, Ill., west of Chicago, he acted in school plays and was a goalie on the soccer team. A photograph taken at his prom in 1982 shows a handsome young man with a messy mop of dark brown hair.

But in 1984, in his freshman year at Beloit College in Wisconsin, Mr. Kauffman suffered a breakdown and was found to have the most severe form of bipolar disorder. He returned home and, after medication stabilized his condition, enrolled in Northern Illinois University. He graduated from there in 1989 with a degree in political science.

For the next year, he worked as a bus driver ferrying senior citizens around DeKalb. In a short local newspaper profile of him in 1990, he listed his favorite book as “Catch-22,” his favorite musician as Elvis Costello, and his favorite moment in life as a soccer game in which he had made 47 saves. A few months later, he followed his mother and stepfather to Atlanta and enrolled in Georgia State University, hoping to earn a master's degree in political science. “He wanted so much to become a political science professor,” Ms. Beik said. But trying to work while attending school proved to be more stress than Mr. Kauffman could handle, Ms. Beik said. In 1992, he suffered his most severe psychotic breakdown. He traveled around the country, telling his parents he intended to work on a political campaign. Instead, he spent much of the year homeless, and his medical records show that he was repeatedly admitted to hospitals.

Mr. Kauffman returned home at the end of 1992, but he never completely recovered, Ms. Beik said. He never worked again, and he rarely dated. In 1994, the Social Security Administration deemed him permanently disabled and he began to receive disability payments. He filed for bankruptcy that year. According to the filing, he had $110 in assets --- $50 in cash, a $10 radio and $50 in clothes --- and about $10,000 in debts.

From 1992 to 2000, Mr. Kauffman did not suffer any psychotic breakdowns, according to his mother. During that period, he took lithium, a mood stabilizer commonly prescribed for people with bipolar disorder, and Stelazine, an older antipsychotic drug. With the help of his parents, he moved to an apartment complex that offered subsidized housing. But in late 1999, a psychiatrist switched him from lithium, which can cause kidney damage, to Depakote, another mood stabilizer. In early 2000, Mr. Kauffman stopped taking the Depakote, according to his mother.

As the year went on, he began to give away his possessions, as he had in previous manic episodes, and became paranoid. During 2000, he was repeatedly hospitalized, once after throwing cans of food out of the window of his sixth-floor apartment. In August, he was institutionalized for a month at a public hospital in Georgia. There he was put on 20 milligrams a day of Zyprexa, a relatively high dose.

The Zyprexa, along with the Depakote, which he was still taking, stabilized his illness. But the drugs also left him severely sedated, hardly able to talk, his mother said. “He was so tired and he slept so much,” Ms. Beik said. “He loved Shakespeare, and he was an avid reader in high school. At the end of his life, it was so sad, he couldn't read a page.”

In addition, his health and hygiene deteriorated. In the 1990 newspaper profile, Mr. Kauffman had called himself extremely well-organized. But after 2000, he became slovenly, his mother said. He spent most days in his apartment smoking. A therapist who treated Mr. Kauffman while he was taking Zyprexa recalls him as seeming shy and sad. “He was intelligent enough to have the sense that his life hadn't panned out in a normal fashion,” the therapist said in an interview. “He always reminded me of a person standing outside a house with a party going on, looking at it.” The therapist spoke on the condition that her name not be used because of rules covering the confidentiality of discussions with psychiatric patients.

As late as 2004, Mr. Kauffman prepared a simple one-page résumé of his spotty work history --- evidence that he perhaps hoped to re-enter the work force. He never did. As Mr. Kauffman's weight increased from 2000 to 2006, he began to suffer from other health problems, including high blood pressure. In December 2005, a doctor ordered him to stop smoking, and he did. But in early 2006, he began to tell his parents that he was having halluci nations of people appearing in his apartment.

On March 16, a psychiatrist increased his dose of Zyprexa to 30 milligrams, a very high level. That decision may have been a mistake, doctors say. Ending smoking causes the body to metabolize Zyprexa more slowly, and so Mr. Kauffman might have actually needed a lower rather than higher dose. A few days later, Mr. Kauffman spoke to his mother for the last time. By March 26, they had been out of contact for several days. That was unusual, and she feared he might be in trouble. She drove to his apartment building in Decatur the next day and convinced the building's manager to check Mr. Kauffman's apartment. He was dead, his body already beginning to decompose.\ An autopsy paid for by his mother and conducted by a private forensic pathologist showed he had died of an irregular heartbeat --- probably, the report said, as the result of an enlarged heart caused by his history of high blood pressure.

Ms. Beik acknowledged she cannot be certain that Zyprexa caused her son's death. But the weight gain it produced was most likely a contributing factor, she said. And she is angry that Eli Lilly played down the risks of Zyprexa. The company should have been more honest with doctors, as well as the millions of people who take Zyprexa, she said. Instead Lilly has marketed Zyprexa as safer and more effective than older drugs, despite scant evidence, psychiatrists say.

Ms. Beik notes that Stelazine --- an older drug that is no longer widely used even though a federally financed clinical trial showed it works about as well as Zyprexa --- stabilized Mr. Kauffman's illness for eight years without causing him to gain weight. “He was on other drugs that worked,” she said.

Court Allows Eli Lilly To Bury Zyprexa Documents\ Thursday, 28 December 2006, 6:01 pm\ Opinion: Evelyn Pringle\ http://www.scoop.co.nz/stories/HL0612/S00342.htm

By Evelyn Pringle

Alaskan attorney, Jim Gottstein, says that after being served with a mandatory injunction, he has returned the internal Eli Lilly documents that he obtained in litigation and provided to the New York Times to the court.

Information from the documents related to Lilly's antipsychotic drug, Zypexa, was highlighted two days in a row in front-page articles in the Times

The documents reveal the illegal marketing schemes used by Lilly to make Zyprexa its best-seller, which the company has managed to keep hidden for years by entering into out of court settlements in civil lawsuits which included confidentiality clauses and by getting judges to place the documents under protective orders to shield them from public view.

For instance, the documents under seal here are from a case where Lilly entered into an out-of-court settlement in June 2005, and agreed to pay $690 million to cover claims by about 8000 Zyprexa victims. But in order to get paid, the plaintiffs were required to sign a confidentiality clause and basically keep their mouths shut about Zyprexa from then on.

Its really comical the way Lilly keeps acting all indignant over the disclosure of these documents as if they contain brand new charges, when the company has been under federal and state investigations related to its off-label marketing of Zyprexa for several years already. The company is also facing Medicaid fraud charges in lawsuits all over the county.

In 1996, Zyprexa was approved for the treatment of adults with schizophrenia, and a few years later, it was approved for short-term treatment of adults with manic episodes associated with bipolar disorder.

Yet despite these extremely limited approved uses, Zyprexa went on to become the top selling antipsychotic worldwide with an estimated 20 million people having used the drug and Lilly's best-selling product, with $4.2 billion in sales in 2005, which translates into 30% of its total revenues.

The documents provided to Times, span a decade and clearly show that the company promoted off-label the sale of Zyprexa for uses not approved by the FDA as being safe and effective. They also reveal that Lilly knew about Zyprexa's link to drastic weight gain and diabetes for years but failed to inform prescribing doctors and consumers.

In fact according to the Times, Lilly knowingly distributed false information to doctors about the risks as late as 2001. On December 21, 2006, the Times reported that the information provided to doctors about the blood-sugar risks of Zyprexa did not match data circulated inside the company after a review of Lilly's clinical trials.

The Times quotes a Lilly report from November, 1999, that shows that after examining 70 clinical trials, Lilly found that 16% of patients taking Zyprexa for a year had gained over 66 pounds. But instead of making these findings public, the company used data from a smaller group of trials that showed roughly 30% of Zypexa patients gained 22 pounds.

Mr Gottstein is not involved in the case in which the judge issued a protective order In re: Zyprexa Products Liability litigation, MDL No. 1596, United States District Court, Eastern District of New York (MDL 1596), "in any manner whatsoever," he says.

He is the leader of, "The Law Project for Psychiatric Rights (PsychRights), a public interest law firm devoted to the defense of people facing forced psychiatric drugging against their will.

Currently, Mr Gottstein represents an Alaskan patient and says the injunction will prevent him from using the Lilly documents to show that the side effects of Zyprexa are well-established by the company's own clinical trials and therefore, his client should not be forced to take such drugs against his will.

In Myers v Alaska Psychiatric Institute, 138 P.3d 238 (Alaska 2006), a case argued by Mr Gottstein last summer, the Alaska Supreme Court ruled that Alaska's forced drugging procedures were unconstitutional because they did not require the court to find such drugging to be in the person's best interests, and that there were no less restrictive\ alternatives.

In order to present the evidence in the case he is handling now, Mr Gottstein is looking to the Alaskan courts to issue a ruling that says his client's right to avoid forced drugging outweighs Lilly's right to keep the information about risks hidden.

He says the documents are highly relevant to a court inquiry, now required in Alaska, before a court can make an informed decision about whether to order forced drugging for his client.

In a December 17, 2006, letter to the court in the New York case, Mr Gottstein stated: "In large part, this state of affairs has been created by the lies told by the manufacturers of psychiatric drugs."

"My impression is," he wrote, "that Eli Lilly's lies about Zyprexa form the basis of the plaintiffs' claims in MDL 1596, but that is not PsychRights' focus."

"PsychRights' focus," he explained, "is helping people avoid being forcibly drugged pursuant to court orders, where the courts have been, in my view, duped by Eli Lilly and other pharmaceutical company prevarications."

"In my view," Mr Gottstein concluded, "the proper disposition of the question would be in favor of my client's right to inform the court of the extreme harm caused by Zyprexa, which Eli Lilly has successfully hidden for so long, while making its billions off the pill."

A court hearing was held in Brooklyn, New York, on a December 18, 2006, on a motion by Lilly, asking the court to order Mr Gottstein to the return the documents to the court, and to bar him from disseminating them any further.

According to the transcript, Lilly also asked the court to require Mr Gottstein to "preserve all emails and all correspondence of any kind, whether it's voice mail, written letters, emails, so that we can pursue a contempt proceeding against both he and Dr Egilman."

Even though the Lilly documents prove that the company knew that Zyprexa was causing diabetes, and kept pushing the drug anyways, potentially harming millions more patients, the judges gave Mr Gottstein hell and threatened to find him in contempt for doing nothing more than warning the public about the side effects of Zyprexa after Lilly concealed the information for a decade.

There is not one single word in the transcripts about Lilly knowingly injuring and killing people with Zyprexa or illegally pushing the drug to unwitting victims for off-label use.

Instead, Judge Brian Cogan, granted Lilly's motion, and told Mr Gottstein's attorney that his client, "deliberately aided and abetted Dr Egilman in getting these documents released from the restriction that they were under, under the protective order. He knew what he was doing, and he did it deliberately."

Judge Cogan went on to tell the attorney, "your client should be on notice that of this moment, he is under a mandatory injunction to return those documents ... to take them down from any websites that he may have posted them on, and to take any reasonable effort to recover them from any sites or persons to which he has delivered them."

On December 18, 2006, at an earlier telephone conference in Brooklyn, Judge Roane Mann also did not utter one word about Lilly's illegal conduct, but instead admonished Mr Gottstein for not playing fair with poor Eli Lilly in making the information about Zyprexa public, stating:

"I personally am not in a position to order you to return the documents. I can't make you return them but I can make you wish you had because I think this is highly improper not only to have obtained the documents on short notice without Lilly being advised of the amendment but then to disseminate them publicly before it could be litigated. It certainly smacks as bad faith."

These judges apparently believe that an expert, such as Dr David Egilman, who is hired to review documents in a case and subsequently learns that people are being seriously injured and killed, should be forced to keep that knowledge a secret if a judge issues a protective order.

There is something very wrong with this picture. It begs the question of how can an ethical doctor not speak if he knows that patients are being harmed

The reason always cited for the need to keep documents under seal is the claim that the information contains trade secrets. However, just as Lilly has done here, drug companies have for too long been abusing the process by using protective orders to hide illegal conduct by concealing documents that show the company is illegally promoting the off-label use of a drug or that a drug can cause serious injuries or that a drug does not work.

In a case like this, if a court truly does not have a choice and is required to seal documents even when they show blatant illegal conduct on the part of a drug company, then Congress had better get busy and pass a law to stop the use the US court system to protect what could very easily be described as corporate murder.

In response to an earlier article on this issue, reader Larry Bone wrote and asked this author, "Is the corruption on this so widespread that no one would dare prosecute?"

"It is criminal behavior," he points out, "on a huge scale that is being virtually totally ignored by the authorities responsible for the public safety."

"I just feel," Mr Bone wrote, "that there has to be an attorney or someone in a judicial or ethical capacity who would have the guts, and persistence to prosecute Lilly."

"It seems incredibly ridiculous," he states, "let alone obscene, that such blatant wrongdoing seemingly continues to be ignored by the legal authorities with jurisdiction over these sorts of cases."

"If these companies believe they have done nothing wrong," he says, "then let them prove their innocence in court."

Ellen Liversridge also wants a criminal investigation of Lilly. She lost her 30-year-old son, Rob, to the adverse effects of the drug. "He gained almost 100 pounds while taking Zyprexa," Ellen says.

"Rob lapsed into a coma," she recalls, "and died of profound hyperglycemia four days later on October 5, 2002."

"I believe that the people who did this should have a criminal trial,"Ellen says. "Enron executives went to prison for wiping out people's life savings," she points out.

"Lilly executives should go to prison," she says, "for knowingly being responsible for people's deaths, shattered families; ruined and grieving families."

Ellen has nothing but praise for the New York Times and its source. "I am grateful to Jim Gottstein for making available this awful truth and hope it results in justice being done."

"If there can ever be justice for a crime as heinous as this," she adds.

Daniel Haszard, of Bangor Maine, feels the same way. In 1996, he was prescribed Zyprexa off-label to supposedly treat Post Traumatic Stress Disorder, and he remained on the drug for 4 years.

Although he paid $250 a month for the drug, Mr Haszard says the drug did not relieve his symptoms of PTSD at all and in early 2000, he was diagnosed with diabetes.

He was shocked to hear the diagnosis, he said, because there was no history of diabetes in his family. Just as thousands of other Zyprexa victims, Mr Haszard did not make the connection between his diabetes and the drug until he saw a commercial for a law firm in December 2005.

Zyprexa causes diabetes, he says, and public health programs are left to pick up the tab for the medial expenses. According to Mr Haszard, "there are now 7 states going after Lilly for fraud and restitution,"related to the promotion of Zyprexa for off-label use and the concealment of its risks.

Dr Stefan Kruszewski, MD, a Harvard trained, certified psychiatrist in adult, adolescent, and geriatric psychiatry, from Harrisburg, Pennsylvania, also finds Lilly's conduct appalling.

"Neither health professionals nor consumers," he states, "can accurately provide information about the risk and benefits of a drug like Zyprexa - or any drug for any condition - without a comprehensive awareness of the risks and benefits."

"If the clinical research data regarding effectiveness, efficacy or safety is sequestered or misrepresented from observation studies, randomized drug trials or meta-analyses," he says, "then it is not possible for any provider to give any patient what he or she needs to make an informed consent."

"At that point," Dr Kruszewski says, "individuals receive drugs that may or may not help them, but always at their own peril."

"Zyprexa causes both a severe metabolic syndrome consisting of obesity, diabetes and cardiovascular problems," Dr Kruszewski advises, "at the same time that it continues to cause neurological side-effects like the older antipsychotics."

"Zyprexa and its antipsychotics cousins," he explains, "were marketed to be safer and easier to tolerate because the pharmaceutical companies said that the newer drugs caused fewer neurological injuries, like restlessness or ‘akathesia,' and tardive dyskinesia."

Those assertions are false he says, and "what we have now is a drug whose massive revenues and promotion are based upon faulty disclosures by Eli Lilly."

Information for injured parties can be found at Lawyers and Settlements.com

Evelyn Pringle\ evelyn-pringle @ sbcglobal.net

(Evelyn Pringle is a columnist for OpEd News and an investigative journalist focused on exposing corruption in government and corporate America)

NARPA

Playing Down the Risks of Zyprexa

The Truth Is Not Free