Zyprexa kid approval based on shady Russian study

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VERACARE <veracare@...> wrote: From: " VERACARE "

<veracare@...>

" Infomail1ahrp (DOT) org " <Infomail1@...>

Date: Mon, 17 Dec 2007 12:46:42 -0500

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Subject: Zyprexa Approval Expose-St sburg Times

ALLIANCE FOR HUMAN RESEARCH PROTECTION

Promoting Openness, Full Disclosure, and Accountability

http://www.ahrp.org and http://ahrp.blogspot.com

FYI

An excellent recap of Eli Lilly's Zyprexa marketing scam was

published in

Florida's Sunday St sburg Times (below).

An analysis by Florida's Agency for Health Care Administration and

University of Southern Florida found:

In 2004, Zyprexa was Florida's most prescribed drug for Medicaid

patients:

312,378.

The dollar amount spent by taxpayers who subsidize Medicaid peaked at

$122.13 million in 2004

As word spread about it inducing diabetes, in 2006 prescriptions

fell to

105,345 and expenditure fell to $27,77 million

As attorney, ph Saunders notes, Zyprexa's blockbuster

status " defies

common sense " inasmuch as it is an exceedingly toxic drug that

induces

life-shortening diseases such as: diabetes, hyperglycemia, metabolic

syndrome.

" Why did it take 10 years to warn people about something they knew

from

their clinical trials? The reason is clear: They were making

billions and

billions of dollars selling it. "

Indeed, as former Eli Lilly-Zyprexa sales rep, Shahram Ahari, points

out,

Zyprexa's serious adverse effects-particularly acute weight gain

which

signals red flags for a host of serious diseases, were visible:

doctors

concerns were downplayed under instructions from Eli Lilly.

Competitor sales reps derisively referred to Zyprexa (generic,

olanzapine)

as " olanza-pig. "

Another question: Why did the FDA fail to interfere with Lilly's

illicit

marketing of a drug FDA officials knew to have failed to demonstrate

a

clinical benefit--and whose diabetes signals were apparent in pre-

marketing

clinical trials?

If FDA's director of the Division of Psychiatry Products is not held

back,

the worst is yet to come:

Though controlled studies and case reports show that kids are even

more

susceptible to Zyprexa's dangerous side effects, Lilly wants the

government's seal of approval for adolescents to use Zyprexa on the

basis of

suspect data from Russia....The FDA is about to say yes.

Especially tragic is the culpability of so-called " advocacy groups "

(such as

NAMI, Mental Health America, and CHADD) all of who have turned a

blind eye

to Zyprexa's devastating effects on patients.

Could it be that they fear endangering the millions of dollars that

Lilly

provides to organizations that disseminate Lilly's promotional

propaganda?

See, for example, Eli Lilly's tooth fairy and " NAMI's Campaign for

the Mind

of America 2007 "

https://www.lillygrantoffice.com/docs/q1_registry_report.pdf

See: http://ahrp.blogspot.com/2007/05/eli-lilly-tooth-fairy.html

http://ahrp.blogspot.com/2007/11/us-psycho-pharmaceutical-

industrial.html

http://www.motherjones.com/news/feature/1999/11/nami.html

Contact: Vera Hassner Sharav

veracare@...

212-595-8974

http://www.sptimes.com/2007/07/29/Worldandnation/The__atypical__dilem

m.shtml

St. sburg Times

A risky drug may get wider market

The FDA may approve Zyprexa for kids, despite its significant side

effects

in adult use.

By ROBERT FARLEY farley@...

December 16, 2007

Graphics:

Zyprexa in Florida: Sources: Florida's Agency for Health Care

Administration

and a USF analysis

photo

Times graphics: Ron Brackett

ph Saunders, who has sued Lilly on behalf of eight patients,

says it

defies common sense that Zyprexa became a bestseller.

Gottstein heads PsychRights, a group that fights unwarranted

forced

drugging and electroshock to mental patients.

Dr. Egilman, facing possible criminal charges, admitted in

writing

that he violated a court order to keep Lilly documents secret.

Shahram Ahari says Zyprexa salesmen were coached how to deal with

doctors

worried about weight and diabetes issues.

Dr. Healy, a pharmacology expert, says that with its side

effects,

" What you've got is a drug that has very little to recommend it. "

It sounds like a cosmic, FDA joke:

The Food and Drug Administration approves the antipsychotic drug

Zyprexa to

treat adults with schizophrenia or bipolar disorder. It becomes a

market

wonder, a bestseller. But the side effects turn out to be dangerous;

some

patients develop diabetes.

Some 30,000 people sue the manufacturer, Eli Lilly. The

pharmaceutical giant

shells out more than $1-billion to settle the cases.

Here comes the punch line:

Though studies show that kids are even more susceptible to Zyprexa's

dangerous side effects, now Lilly wants the government's seal of

approval

for adolescents to use it. And the FDA is about to say yes.

Like a mounted animal head hung as a trophy from the hunt, a framed

copy of

a $2.8-million check from Bayer pharmaceutical hangs in the law

office of

ph Saunders. The check says: It's my business to sue drug

companies, and

I'm good at it.

Saunders practices in Pinellas Park, but hundreds of lawyers like

him across

the country have found a niche suing Lilly.

He has eight Zyprexa clients. Most are psychotic. Most suffer from

diabetes,

which can cause kidney failure, heart disease, liver damage,

blindness.

They were prescribed Zyprexa during the time doctors swooned over

the big

new thing. Approved by the FDA in 1996, Zyprexa was one of a new

class of

drugs called atypicals, marketed as powerfully effective for people

suffering the dreadful psychotic breaks of schizophrenia and bipolar

disorder.

And -- this was key -- the new drugs were less likely to cause the

tremors

and facial tics that sometimes accompanied older drugs

Zyprexa was deemed so safe, doctors began prescribing it " off-label "

to

treat depression, anxiety, ADHD, even sleeplessness. As it turned

out,

studies would show that Zyprexa may be the most effective of the new

class

of antipsychotic drugs, but it's also most likely to cause serious

weight

gain and elevated blood sugar levels.

Saunders says you can't win a lawsuit against a drug company just

because

you suffer a side effect. But pharmaceuticals do have a legal

responsibility

to warn doctors about known risks.

The tens of thousands of lawsuits contend that Lilly did not fully

disclose

risks it discovered during studies conducted to get FDA approval for

Zyprexa, risks that became more apparent in the years after the drug

hit the

market.

The preapproval studies lasted six weeks, not nearly time for

diabetes to

manifest itself, Saunders says, but there were red flags. Some 29

percent of

participants gained significant amounts of weight. Rapid weight gain

puts

people at higher risk of developing diabetes.

Lilly spokeswoman Marni Lemons allows that a majority of people who

take

Zyprexa gain a lot of weight. And some of them develop diabetes.

But only a small percentage of those who gain weight on Zyprexa

develop

diabetes. Also, people with schizophrenia and bipolar disorder are

at higher

risk of diabetes no matter what drug they take. " It's a very

complicated

subject, " Lemons said. Bottom line: No data directly finds that

Zyprexa

causes diabetes.

So why did Lilly pay $1.2-billion to settle 30,000 claims?

" Even when a company has a really strong defense, as we believe

Lilly did,

going to court poses very real financial and business risks, " Lemons

said.

" Lilly has a responsibility to its shareholders and employees -- as

well as

to health care professionals and patients -- to move beyond this

litigation

at the lowest possible cost. "

Saunders counters that Lilly treats lawsuits as a cost of doing

business:

$1-billion in settlements sounds like a lot, he says, but it's chump

change

compared to the tens of billions the company has made since Zyprexa

came on

the market.

Lilly has more than private attorneys to worry about. Nine states

have sued,

claiming the company illegally promoted unapproved uses of Zyprexa

and

downplayed its side effects. The states want to be reimbursed

hundreds of

millions for Medicaid dollars they paid for Zyprexa.

In 2003, the FDA directed that not only Zyprexa, but all atypical

antipsychotics carry a warning about increased risk of hyperglycemia

and

diabetes.

Lilly continued to market its drug as more effective but no more

dangerous

than its competitors. Only this fall did the company agree to change

Zyprexa's label to state that its tendency to increase blood sugar

levels,

another diabetes risk factor, is higher than its competitors.

Asked Saunders: " Why did it take 10 years to warn people about

something

they knew from their clinical trials? The reason is clear: They were

making

billions and billions of dollars selling it. "

* * *

The telephone call that Gottstein took late last year was a

bolt from

the blue.

An attorney in Alaska, Gottstein heads a group called PsychRights,

which

presses litigation against forced psychiatric drugging and electric

shock.

The caller, a stranger Gottstein never had spoken with, said he had

documents that could help lead Gottstein's group to the promised

land.

The caller, Egilman, worked as a consultant for a law firm

that had

thousands of clients suing Lilly over Zyprexa. In that job, he was

given

access to thousands of pages of internal Lilly documents, but they

were

under protective order; it was illegal for him to make them public.

What happened next is disputed, but a quite furious U.S. district

judge,

Jack B. Weinstein, determined this is how his court order was

violated:

At the suggestion of a New York Times reporter, Egilman called

Gottstein and

-- wink, wink -- suggested he find a separate case in which he could

subpoena the Lilly documents from him. Gottstein could get copies to

the

aforementioned reporter before Lilly and the courts could act to

stop it.

The deed done, Lilly officials were furious. As Gottstein put

it, " They came

after me like a Panzer division. "

Judge Weinstein, who called it a conspiracy to assist the stealing of

protected documents, tried to get the copies back. But they had hit

the

Internet.

There were internal memos, showing Lilly's marketing strategy aimed

at

downplaying weight gain and any link to diabetes.

There was a memo from a Lilly employee in 2000 fretting that doctors

the

company hired to study the diabetes connection had warned

that " unless we

come clean on this, it could get much more serious than we might

anticipate. "

There were letters from doctors who raved about the drug's

effectiveness but

warned Lilly that patients were developing diabetes at an alarming

rate.

Like this one from 2001, from Dr. Clif Tennison, in Knoxville: " It is

troublesome, frustrating and occasionally irritating to repeatedly

hear the

official line that a relationship between Zyprexa and diabetes is

unclear,

that diabetes is known to occur more frequently in mentally ill

people with

or without meds, etc. We know that.

" But we also know that our Zyprexa patients gain weight and that

they do

develop diabetes. It feels as if our concerns are being dismissed,

and that

if we would just listen to the experts, we wouldn't worry about this

anymore. "

Egilman and Gottstein paid a price for making the documents public.

Threatened with criminal prosecution, Egilman signed a mea culpathat

said he

had provided an " incomplete subset " of the Lilly documents. He paid

the

company $100,000, which Lilly donated to charity.

Gottstein, who maintains he did nothing improper, says Lilly is

still going

after him, for civil sanctions that could ruin him financially and

for

criminal contempt. He says it has threatened to go after his law

license.

When he answered the phone that day, who knew what lay ahead? " I do

think it

was important to get this information out. People should be informed

of the

risks before they decide to take these drugs. So for me, it was

worth it. "

* * *

Spring 1998. Like zillions of undergrads, Shahram Ahari was finishing

college, looking for that first job. He had finished Rutgers

University with

a degree in molecular biology, biochemistry and Asian studies. A

friend's

brother landed him an interview with Eli Lilly. The job, salesman.

Ahari knew zip about pharmaceutical sales, but he loved what he

heard:

$50,000 base salary, $10,000 to $15,000 annual bonuses, stock

options, a

free car, great health benefits. Meals on a hefty expense account.

To hawk Zyprexa, he says, the pitch was simple: " Encourage doctors

to be the

first on their block with a brand-new toy. "

When he made sales calls, he was armed with data from an independent

company

that tracked every prescription the doctor made that month. It helps

to know

that the doc you are about to pitch prescribes more of your

competitor's

drug, say, Risperdal. You can take some gratuitous pot shots at

Risperdal in

your pitch.

The job mostly was about befriending doctors and leveraging their

emotions,

Ahari says, though favoring them with goodies didn't hurt. Salesmen

wooed

doctors with free samples, treated them to expensive dinners and

paid them

to give speeches at seminars.

" It practically sold itself, " said Ahari, who sold Zyprexa in New

York from

1998 to 2000.

The gravy train hit some bumps. Reps started hearing from doctors

concerned

about patients " blimping up. " Competitors hammered them on it,

derisively

twisting Zyprexa's generic name, olanzapine, into " olanza-pig. "

The Zyprexa sales reps eagerly awaited word from Lilly's brand team

on how

they should deal with the weight/diabetes issue. Ahari says this is

what

they came up with: Tell doctors to instruct patients to drink a

glass of

water before and after they eat, to suppress appetite.

" We'd have to do it with a straight face, " Ahari said, " and after a

while,

it just became uncomfortable. "

With doctors he knew well, he said his pitch was blunt: " Would you

rather

have a skinny, unwell patient or a fat, stable one? "

Doctors started reporting patients developing diabetes. " That was a

big,

scary thing, " Ahari said. If the FDA required that Zyprexa carry a

black box

warning about diabetes, " it would have been death, market-wise. "

He says sales reps were instructed to deflect the issues of weight

gain and

diabetes. " We were taught to downplay it and negate it, or to change

the

topic. "

Lemons, the Lilly spokeswoman, says the company can't be certain

what every

sales manager told their sales reps, but " that has never been our

corporate

policy. " She questioned Ahari's objectivity because she said he is

now a

paid witness for trial attorneys taking on pharmaceutical companies.

Ahari says he was a paid witness in just one case, which was about

preserving the confidentiality of physicians' prescribing patterns.

Today he does public health research on biological disaster

preparedness at

the University of California, San Francisco. He lectures on how

sales reps

influence physicians, and he has applied to medical school. Like many

critics, Ahari came to feel Zyprexa was effective, appropriate for

many

people. But he believed that the brass at Lilly downplayed the

weight and

diabetes problems because the clock on the patents was ticking. The

thinking

was, " we may as well milk it while we can. "

* * *

Even with all the lawsuits, Zyprexa remains Lilly's best-seller. Some

22-million people have taken it. In just the first six months this

year,

sales topped $2.3-billion.

Lilly can ride the Zyprexa money machine until its patent runs out

in 2011.

But thanks to a carrot offered by the FDA, the company is in line to

get an

extra six months of exclusivity. That will allow Lilly to keep

making top

dollar before generic versions can come on the market and the price

falls.

That's where expanding the government's seal of approval to use

Zyprexa on

adolescents comes in.

Though the FDA approved Zyprexa only for use on adults with

schizophrenia or

bipolar disorder, psychiatrists prescribe it " off label " to

children.

Drug companies had no incentive to study whether giving powerful

antipsychotics to kids is safe, not with doctors already prescribing

their

drugs to children by the fistful.

That's why the FDA offered to extend exclusivity of the atypical

antipsychotics by six months if the companies studied their effect in

children.

It has made for a bizarre left-hand/right-hand situation.

On one hand, federal and state investigators are looking into

whether Lilly

and other drug companies downplayed risks and illegally promoted

their drugs

for unapproved uses. On the other hand, the FDA is looking into

expanding

the approved use of the identical drugs. Already this year, the FDA

has

approved the atypicals Risperdal and Abilify for use in adolescents.

Evidence suggests that the dangerous side effects of Zyprexa in

adults are

more pronounced in children.

A study published in August compared several atypical antipsychotics

in the

treatment of early onset schizophrenia. Kids on Zyprexa gained so

much

weight, the Zyprexa arm of the study was discontinued. Another study,

published in the American Journal of Psychiatry in October, found

Zyprexa

effective in treating bipolar mania in adolescents. But in the three-

week

study, kids on average gained more than 8 pounds and had elevated

glucose

and cholesterol levels.

In an accompanying editorial, Dr. Jon M. McClellan, an associate

professor

of psychiatry at the University of Washington, wrote that " the long-

term

consequences of obesity, dyslipidemia and insulin resistance -- and

the risk

of diabetes and cardiovascular disease -- raise serious questions

over the

risk-benefit ratio of olanzapine as a first-line treatment in

juveniles. "

McClellan said in an interview that parents tell him their kids on

Zyprexa

are always hungry, ravenous even. " A kid comes in and a week later

they've

gained 4 pounds, they look puffy, " he said.

Adults taking Zyprexa may gain 5 to 15 pounds in a year, he says,

but kids

may gain that in three weeks. Over time, some have gained more than

50

pounds.

A three-person FDA panel that reviewed Lilly's application for

approval of

Zyprexa for adolescents had reservations about the studies and

initially

recommended denial. The vote was unanimous.

But P. Laughren, director of the FDA's Division of Psychiatric

Products, said the FDA should not follow the expert panel's

recommendation.

Lilly had submitted two studies, with patients roughly split between

sites

in the United States and Russia. The three-member FDA team was

troubled that

the positive results mostly came from the Russian sites. But

Laughren noted

that FDA inspectors visited the Russian sites and " they found no

evidence

for fraud. "

He said the side effects in children -- weight gain, somnolence,

sedation,

fatigue, dizziness and dry mouth -- were similar to what has been

seen in

adults, " however, with some differences in magnitude. " Those

differences

need to be reflected on the labeling, Laughren said in a memo, but he

concluded that Zyprexa is " effective and acceptably safe " for

treatment of

adolescents with schizophrenia and bipolar disorder.

One of the world's most prominent pharmacology experts shudders at

the

prospect of the FDA approving Zyprexa for adolescents.

Dr. Healy, a professor of psychiatry at the University of

North Wales,

says that even in adults, Zyprexa should be used only as a backstop,

after

other antipsychotics have been tried and failed.

" It ought not to be used in children at all, " he said. " It is going

to be

marketed as a safe and gentle drug. It is not a safe and gentle

drug. I

think it's an extremely dangerous drug. The idea that it's going to

be given

to children on a large scale is quite scary. "

Farley can be reached at farley@...

or (727) 893-8603.

________________________________

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