Eli Lilly & Co. urged doctors
to prescribe Zyprexa [olanzapine] for elderly patients with dementia, an unapproved use for the antipsychotic, even though
the drug-maker had evidence the medicine didn’t work for such patients, according to unsealed internal company documents.
In 1999, four years after Lilly
sent study results to the U.S. Food and Drug Administration showing Zyprexa didn’t alleviate dementia symptoms in older
patients, it began marketing the drug to those very people, according to documents unsealed in insurer suits against the company
for overpayment.
Regulators required Lilly and other antipsychotic
drug- makers in April 2005 to warn that the products posed an increased risk to elderly
patients with dementia [of death]. The documents show the health dangers in marketing a drug for an unapproved use, called
off-label promotion, said Sidney Wolfe, head of the health research group at Public Citizen in Washington.
“By definition, off-label
means there is no clear evidence that the benefits of a drug outweigh the risks,” Wolfe said. “The reason why
off-label promotion is illegal is that you can greatly magnify the number of people who will be harmed.”
In 1999, when Lilly began its marketing
push, Zyprexa’s only approved use was for patients suffering from schizophrenia, according to the FDA. In 2008, Zyprexa
was Lilly’s best-selling drug, with $4.7 billion in sales, while anti-psychotics as a group topped U.S. drug sales last year, with $14.6 billion.
Seven Studies
In a request for a December 2003
meeting over a proposed label change, Lilly told the FDA that data from seven studies showed Zyprexa didn’t alleviate
symptoms of Alzheimer’s or other dementia.
The studies found death rates among older dementia patients taking Zyprexa were “significantly greater”
than those who didn’t get the medicine, the company said, according to the unsealed documents.
“Plaintiffs are releasing one-sided,
cherry-picked documents obtained in discovery to selected news media in an effort to try their cases in the media,”
said Lilly spokeswoman Marni Lemons, who added that the company will fight the lawsuit. She declined
to answer specific questions about the studies.
Lilly pleaded guilty in January
to a federal misdemeanor charge of illegally marketing Zyprexa for off-label uses to elderly consumers. The company admitted
illegal promotions from September 1999 through March 2001, while denying such practices beyond that date.
Medical Journals
The documents also revealed Lilly officials wrote medical journal studies about Zyprexa
and then asked doctors to put their names on the articles, a practice called “ghostwriting.”
Lilly employees compiled a guide
to hiring scientists to write favorable articles, complained to journal editors when publication was delayed and submitted
rejected articles to other outlets, according to the documents.
Lilly’s internal documents,
which number about 10,000 pages, were unsealed as part of suits against the drug-maker by health insurers and pension plans
seeking to recoup monies spent on Zyprexa. The insurance plans contend the papers indicate that Lilly promoted the antipsychotic
to doctors treating elderly patients even after March 2001.
The plaintiffs cite documents including
a 2002 business plan calling for expanding prescriptions in off-label use. They also point to notes from Lilly sales representatives
through 2003 recording efforts to press doctors to prescribe elderly patients Zyprexa for mood symptoms, irritability and
insomnia.
$6.8 Billion in Damages
Insurers and other so-called third-party
payers contend Lilly should pay as much as $6.8 billion in damages for downplaying Zyprexa’s health risks, including excessive weight gain and the risk of contracting
diabetes, and marketing the drug for unapproved uses to pump up profits.
Bloomberg News obtained copies of the documents
after U.S. District Judge Jack Weinstein in Brooklyn,
New York, ordered their release on May 1. In September, Weinstein allowed insurers
and other payers to sue Lilly as a group after finding “sufficient evidence of fraud” to let the case go to trial.
Lilly appealed that ruling.
The Indianapolis-based drug-maker
agreed in January to pay $1.42 billion to the U.S. government and more than 30 states to settle off-label marketing allegations
over Zyprexa. The agreement included a $615 million penalty for the federal criminal charge.
Lilly has paid $1.2 billion so
far to settle more than 32,000 individual claims by patients, the company said in an April 30 securities filing. About 140
claims remain, Lilly reported.
12 States
The company also faces suits from
12 states over its Zyprexa marketing practices. Cases brought by South Carolina
and Connecticut officials are set for trial later this year.
The unsealed documents support the claims of
the insurers suing Lilly, said lawyer Thomas Sobol, of Seattle-based Hagens Berman Sobol Shapiro LLP. His firm
represents the plaintiffs suing the drugmaker for overcharging on Zyprexa and provided Bloomberg News with copies of the documents.
Bloomberg News filed a letter brief
asking the court to unseal the documents.
Zyprexa was initially approved
in 1996 for use with schizophrenia sufferers. In 2000, Lilly received the FDA’s approval to sell it to those dealing
with the mania stage of bipolar disorder.
The drug has never been approved for use with
dementia patients, according to the FDA’s Web site.
Even before the drug was on the
market, Lilly researchers were eyeing whether elderly dementia patients could benefit from taking the antipsychotic, according
to the unsealed documents.
Company Study
A 1995 company study of users taking
between 1 to 8 milligrams of Zyprexa “did not show efficacy in alleviating the psychotic symptoms and behavioral disturbances
in elderly” patients suffering from “primary degenerative dementia of the Alzheimer’s type,” according
to a study summary that was unsealed.
The company also noted that three
patients taking Zyprexa died during a study or within 30 days of its completion, while only one control-group patient expired,
according to the unsealed documents.
J. Alan Webber, a Lilly executive,
acknowledged in a Feb. 16, 1995, note that FDA official Paul
Leber wasn’t impressed with study results in connection with Zyprexa’s effectiveness in treating older dementia
patients.
“Dr. Leber was not enthusiastic
about study HGAO (psychotic demented elderly) with respect to the indication for use, and extensive discussion did not resolve
the disagreement,” Webber said, according to the documents.
Back to the FDA
In 1998, Lilly went back to the
FDA seeking approval to market Zyprexa to those battling Alzheimer’s, the most common form of dementia, the company
said in its 2003 request for a meeting on a proposed label change. Lilly withdrew its bid to promote Zyprexa for Alzheimer’s
cases in 1999, according to the document.
In a November 2000 memo to Lilly
salespeople, company executives said the dementia marketing initiative was abandoned because the FDA questioned Zyprexa’s
effectiveness in treating the ailment.
“It was withdrawn due to
vagueness on the FDA’s part regarding a definition of efficacy,” Lilly officials said in the document.
In a 2003 memo to FDA regulators
citing the clinical studies, Lilly researchers acknowledged the death rates among older dementia patients on Zyprexa in the
reviews were two times higher than their counterparts taking placebos.
Patient Deaths
Deaths among the patients taking
Zyprexa in the studies were “significantly greater than placebo-treated patients (3.5 percent v. 1.5 percent, respectively),”
Lilly officials said, according to the unsealed documents.
The studies didn’t find Zyprexa
was effective in treating dementia, the company acknowledged in this document.
Lilly recognized this earlier,
according to a 2002 document entitled “Zyprexa in serious mental illness (65 plus years) -- A Strategy Review.”
“The treatment of serious
mental illness for people over the age of 65 has been identified as a growing opportunity for Zyprexa,” the authors
wrote. “Unfortunately, attempts to gain the data to support an application for an indication in the treatment of dementia
have to date been unsuccessful.”
Lilly, which first marketed Zyprexa
to psychiatrists, sought to expand its customer base in 1999 by focusing on long term-care facilities, particularly nursing
homes, according to the unsealed documents.
Primary Care Physicians
It later began targeting primary care physicians,
known as PCPs, as another potentially lucrative Zyprexa market. Such physicians frequently deal with dementia patients, according
to the unsealed files.
Another benefit to the strategy
was that many of those practitioners were “unaware of Zyprexa weight gain issue,” according to a December 1999
Lilly sales memo, referring to one of the drug’s possible side-effects.
Lilly viewed dementia as the “key”
to the elderly and PCP markets, according to an undated document, “Elderly
- PCP Sales Aid.” In that paper, executives urged salespeople to “utilize
dementia and symptoms as entry.”
Lilly marketing executives envisioned
expanding “Zyprexa’s market by redefining how primary care physicians treat mood, thought and behavioral disturbances,”
according to the December 1999 memo. The strategy included: “Focus message patients; symptoms and behaviors (rather
than diagnoses),” according to the unsealed internal company documents.
Zyprexa Sales
Lilly officials in 2002 reported
Zyprexa sales grew due to “an expanding prescriber base in primary care, off-label use including PTSD and sleep,”
according to a document called “Zyprexa Business Summary,” referring to post-traumatic stress disorder. The company’s
goal was to reach $6 billion in sales by 2006, according to a July 2002 Zyprexa marketing plan.
Lilly’s long-term care unit
also saw Zyprexa sales rise 2.9 percent in the second quarter of 2002 as sales of Risperdal, Johnson & Johnson’s
rival antipsychotic, fell, according to the 2002 marketing plan.
At that time, long-term care sales
made up about 20 percent of Zyprexa prescriptions, according to the summary. Of that number, 65 percent were written for nursing-home
patients.
Overall, prescriptions for older
patients were the “2nd biggest money-producing segment” for Zyprexa in the U.S., according to a Feb. 15,
2002, e-mail from Lilly researcher Peter Feldman to Denice Torres, the company’s global marketing director.
Internal Memos
In that e-mail, Feldman said company
officials were saying in internal memos that they were going to stop studying Zyprexa’s potential health benefits for
elderly consumers.
That would risk “killing
the goose that lays the golden eggs to save on poultry feed costs,” Feldman said in the unsealed messages.
Torres assured him older consumers
would continue to be a prime target for Zyprexa sales, according to the e-mail.
“Elderly remains an important
aspect of target PT and affiliate focus,” she said in the message.
Increased Zyprexa sales to elderly
patients also won Lilly’s long-term care unit praise in a 2003 newsletter unsealed as part of the documents.
“For two consecutive years,
you have been on top and have turned in above-plan performance,” Grady Grant, Lilly’s national sales director,
wrote in the newsletter. “I look forward to working with you as we set our sights on overtaking Risperdal as the number
one antipsychotic in the marketplace!”
‘Driving Force’
“Once again you have all
shown that LTC is a driving force for Zyprexa in the US affiliate in 2002,” Mike Murray, another Lilly executive, wrote in the
newsletter. “We must continue to accelerate the growth of Zyprexa.”
Unsealed documents also showed
Lilly salespeople prodded doctors to prescribe the drug for off-label uses, according to “call notes” Lilly turned
over in lawsuits against the drugmaker. Portions of some call notes, which record sales visits to doctors, are cited in a
recently unsealed June 15, 2007, filing by the insurance plans.
One sales representative wrote
in a March 7, 2003, note she’d persuaded a doctor to write
Zyprexa prescriptions for use in “elderly pts, help sleep and irritability.” Another asked a doctor to try Zyprexa
“in elderly who are not thinking clearly and are suspicious and hostile,” according to an Aug. 31, 2001, note.
Common Adverse Effects
In June 2004, Paula Rochon, a senior
scientist at the Institute for Clinical Evaluative Sciences in Toronto, published a literature review in the British Medical
Journal showing there were only five trials available analyzing antipsychotics’ effect
on the elderly, and that in those trials, adverse effects were common.
In May 2008, Rochon found that
atypical antipsychotics triple the risk of a patient’s death or hospitalization
within a month of starting therapy, according to research published in the Archives of Internal Medicine. About 17 percent
of nursing home patients suffering from dementia are prescribed an antipsychotic within 100 days of their admission, according
to her study. [The actual percentage is much higher.]
The insurance plans, states and
former Zyprexa patients suing Lilly also claim company officials hid the drug’s health risks and failed to properly
warn patients they could develop diabetes by taking the medicine. Former users contend the drug leads to increased weight
gain, which can spark the disease.
In 2001, marketing executives advised
salespeople not to duck questions about whether Zyprexa caused some users to gain weight, according to an internal memo.
“Acknowledge weight gain
but present it as a manageable side effect,” Lilly advised its sales force, according to the documents. “With
most customers, we will continue to address the diabetes concern only when it arises,” the December 2001 document said.
“Get back to selling!”
The case is UFCW Local 1776 and
Participating Employers Health and Welfare Fund v. Eli Lilly and Co., No. 05-CV-04115, U.S. District Court, Eastern District
of New York (Brooklyn).
To contact the reporters on this story: Margaret Cronin Fisk in Detroit at mcfisk@bloomberg.net; Elizabeth Lopatto in New York at elopatto@bloomberg.net; Jef Feeley in Wilmington, Delaware at jfeeley@bloomberg.net.
Last Updated:
June 12, 2009 00:01
EDT
From http://en.wikipedia.org/wiki/Zyprexa
90% of users
experience weight gain, increased risk of hyperglycemia and diabetes. Wikipedia
lists over 20 serious side effects. Of interest is “a placebo-compared study of six Macaque monkeys receiving olanzapine between 17 and 27 months, a significant brain volume and weight decreases
(8-11%) were detected.”
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, another
study showed 16% of Zyprexa patients gained at least 30 kg (66 pounds) in one year, and some patients have reported gaining
100 pounds or more.
In 2006, 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.[31]
In 2002, British
and Japanese regulatory agencies warned that Zyprexa may be linked to diabetes, but even after the FDA issued a similar warning
in 2003, Lilly did not publicly disclose their own findings.
Eli Lilly agreed
on January 4, 2007 to pay up to $500 million to settle 18,000 lawsuits from people who claimed they developed diabetes
or other diseases after taking Zyprexa. Including earlier settlements over Zyprexa, Lilly has now agreed to pay at least $1.2
billion to 28,500 people who claim they were injured by the drug. At least 1,200 suits are still pending, the company said.
About 20 million people worldwide have taken Zyprexa since its introduction in 1996.[32] On January 8, 2007, Judge Jack B. Weinstein refused the Electronic Frontier Foundation's motion to stay his order.[33]
On January 15, 2009 Eli Lilly plead guilty to a misdemeanor charge of illegally marketing Zyprexa for off-label use,
and agreed to pay $1.4 billion
Lilly 'ghostwrote' Zyprexa studies, documents show
By Tracy Staton, June 12, 2009, FirecePharma at http://www.fiercepharma.com/story/lilly-ghostwrote-zyprexa-studies-documents-show/2009-06-12?utm_medium=nl&utm_source=internal
Eli Lilly prodded doctors to prescribe Zyprexa for dementia patients even though it had data showing the drug
didn't help those patients, Bloomberg reports, based on
internal company documents made public as part of a lawsuit. Plus, the company "ghostwrote" journal articles supporting the atypical antipsychotic, then scouted for doctors to append their bylines, the documents
show. Lilly also compiled a guide to hiring scientists to write favorable articles.
Aggrieved by the document release, Lilly defended itself: "Plaintiffs are releasing one-sided, cherry-picked documents
obtained in discovery to selected news media in an effort to try their cases in the media," Lilly spokeswoman Marni Lemons
told Bloomberg, adding that the company will fight the lawsuit.
She wouldn't answer specific questions, however.
The unsealed documents were submitted as evidence in lawsuits against the drugmaker, filed by health insurance
companies and pension plans that want to be repaid for their spending on Zyprexa. The plaintiffs are asking for as much as
$6.8 billion in damages. Lilly already settled off-label marketing claims with the U.S. government and several states--for
$1.42 billion, including a $615 million criminal penalty. The company has paid $1.2 billion to settle individual patient claims,
Bloomberg reports. For comparison's sake, Zyprexa sales
for 2008 amounted to $4.69 billion, down slightly from $4.76 billion in 2007.
