Fwd: [SSRI-Research] GlaxoSmithKline CEO: We had to absorb a number of hits

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Mon, 16 Feb 2004 17:18:03 -0000

[sSRI-Research] GlaxoSmithKline CEO: " We had to absorb a number of

hits "

 

ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

Promoting openness and full disclosure

http://www.ahrp.org

 

FYI

 

Antidepressant drug safety issues are beginning to have a financial

impact. Dow Jones reports: " GlaxoSmithKline PLC said its net income

fell 6% in the fourth quarter, hurt by previously announced legal

costs related to its anti-inflammatory product Relafen, and weaker

sales of the antidepressant Paxil. " " We had to absorb a number of

hits, " Chief Executive Jean-Pierre Garnier said, including generic

competition to antidepressant Paxil and legal costs of £228 million

in the latest quarter.

 

Those legal fees come from what some are calling corrupt corporate

practices. A report in the Canadian Medical Association Journal

(CMAJ, March

2) cites " an internal document [that] advised staff at the

international drug giant GlaxoSmithKline (GSK) to withhold clinical

trial findings in 1998 that indicated the antidepressant paroxetine

(Paxil in North America and Seroxat in the UK) had no beneficial

effect in treating adolescents. "

 

AHRP has obtained a copy of the October 1998 document (soon to be

posted on our website). The document refers to the following studies

in children: Study 329 was conducted between 1993–1996, showing that

the Seroxat/ Paxil was no more effective than placebo in treating

pediatric depression. Study 377 which found that placebo was actually

more effective than Paxil. These studies' failure to demonstrate a

benefit for children / adolescents resulted in the company's

withholding of the findings from the FDA and other regulatory

agencies. The internal company memo states: " Data from these 2

studies are insufficiently robust to support a label change and will

therefore not be submitted to the regulatory authorities. "

 

Two other studies are discussed in the document: Study 511 conducted

in France, and study 453 conducted in adolescents in the US. These

have never been published.

 

Study 329 has recently been analyzed by Dr. David Healy, the foremost

international expert on antidepressant drugs and the original

clinical trial data that tested these drugs. His analysis of the

original clinical trial reports reveal that among the 93 adolescents

taking Seroxat /Paxil in study 329, there were 5 serious cases

of " emotional lability " (suicidal ideation/ gestures). Among the 95

adolescents taking the comparison treatment, imipramine (Tofranil),

there was 1 such case, and among the 89 subjects receiving placebo

there were 0 suicidal acts.

See: David Healy, MD presentation at AHRP Press Briefing, Feb. 2,

2004, slide 5. http://www.ahrp.org/risks/SSRI0204/HealyLink.html

 

Nevertheless, a report published in the Journal of the American

Academy of Child and Adolescent Psychiatry (2001;40 [7]:762-72) in

2001, claims that the findings for study 329 were positive. Contrary

to the actual data, the authors reported only 1 serious adverse event

related to treatment — headache in 1 patient. Contrary to the actual

negative findings that are acknowledged in the secret 1998 company

memo, the authors assured journal readers (mainly

physicians): " paroxetine is generally well tolerated and effective

for major depression in adolescents. "

 

* The Guardian (UK) first revealed the content of GSK's confidential

memo on February 3, 2004.

See: http://www.ahrp.org/infomail/04/02/05a.html

 

The CMAJ report states that in 2003, Seroxat (Paxil) sales amounted

to almost $4.97 billion worldwide.

 

Drug manufacturers are currently in a position to control what

portion of the data gets published--not only in promotional material

planted in the popular press and media, but in (supposedly) peer-

reviewed, prestigious scientific journals.

See: http://www.ahrp.org/infomail/04/01/29.html

 

THE WASHINGTON POST Antidepressant Makers Withhold Data on Children,

http://www.washingtonpost.com/ac2/wp-dyn/A58130-2004Jan28?

language==printer

 

FDA's Commissioner, Dr. Mark McClellan should be asked to explain why

senior FDA officials are turning a blind eye and a deaf ear to

compelling evidence linking antidepressant drugs to suicidal and even

homicidal acts by children and teenagers? Senior FDA officials have

known for years that these drugs failed to demonstrate a benefit for

children. Senior FDA officials have known at least since 1996 of a

drug-linked aggression / suicidal risk for children. See documented

comments submitted by AHRP to FDA's advisory committee:

http://www.ahrp.org/risks/SSRI0204/AHRP.html

 

The following questions require answers:

Why do senior FDA officials ignore the test data in the agency's own

files?

 

Why did senior FDA officials prohibit their own medical officer from

presenting his findings at a public advisory committee meeting?

 

Why did senior FDA officials refuse to allow experts who have

analyzed all the clinical trial data--not selectively reported data--

to present their findings at the public advisory committee hearing,

on Feb 2?

 

FDA's advisory committee urged the FDA to issue warnings about these

risks now without delay. But senior FDA officials appear to disregard

the victims of drug-induced, potentially lethal effects. And these

officials appear disinclined to follow the agency's own advisory

committee recommendations. To whom are these senior FDA officials

accountable?

 

 

Contact: Vera Hassner Sharav

Tel: 212-595-8974

e-mail: veracare

 

~~~~~~~~~~~~~~~~

http://www.cmaj.ca/pdfs/page783.pdf

Drug company experts advised staff to withhold data about SSRI use in

children PHARMACEUTICAL INDUSTRY DOI:10.1053/cmaj.1040236

 

A 1993–1996 INDUSTRY STUDY SHOWED THAT PAROXETINE WAS NO MORE

EFFECTIVE THAN PLACEBO IN TREATING PEDIATRIC DEPRESSION. Health

Canada ANALYSIS CMAJ • MAR. 2, 2004; 170 (5) 783

 

An internal document advised staff at the international drug giant

GlaxoSmithKline (GSK) to withhold clinical trial findings in 1998

that indicated the antidepressant paroxetine (Paxil in North America

and Seroxat in the UK) had no beneficial effect in treating

adolescents. Paroxetine is 1 of 6 drugs in the class of selective

serotonin reuptake inhibitors (SSRIs) that Britain and the US have

since banned for pediatric use because of increased risk of suicide.

On Feb. 2, Health Canada issued a public warning that the pediatric

use of 7 antidepressants —paroxetine, bupropion (Wellbutrin),

citalopram (Celexa), fluvoxamine (Luvox), mirtazapine (Remeron),

sertraline (Zoloft) and venlafaxine (Effexor) — should proceed only

after consultation with the treating physician " to confirm that the

benefits of the drug still outweigh its potential risks. "

 

The GSK internal document obtained by CMAJ offers a glimpse into the

inner workings of a drug giant. Entitled " Seroxat/Paxil Adolescent

Depression: Position piece on the phase III clinical studies, " the

confidential document was prepared by the Central Medical Affairs

team (CMAt), a division of SmithKline Beecham (which subsequently

merged with Glaxo Wellcome to form GSK). The document provides

guidance on how to manage the results of 2 clinical trials conducted

into the efficacy of paroxetine (Seroxat). Given that the clinical

trials results were, according to the document, " insufficiently

robust " to support an application to regulatory authorities for a

label change approving Seroxat for use in pediatric depression, CMAt

recommended the firm " effectively manage the dissemination of these

data in order to minimize any potential negative commercial impact. "

 

Sales for Seroxat amounted to almost $4.97 billion worldwide in 2003.

 

Study 329, conducted in the US from 1993–1996, was the largest trial

to date on using an SSRI in a pediatric population. According to the

document, the results indicated paroxetine was no more effective than

placebo. In the other trial, Study 377, carried out in Europe, South

America and elsewhere, placebo was actually more effective than the

antidepressant. The CMAt document advised that " Positive data from

Study 329 will be published in abstract form at the [European College

of Neuropsychopharmacology] meeting " in November 1998 and that " a

full manuscript ... will be progressed. " It also stated that " It

would be commercially unacceptable to include a statement that

efficacy had not been demonstrated, as this would undermine the

profile of paroxetine. "

 

GSK spokeswoman Jill McKinlay-Morris said that " the memo draws an

inappropriate conclusion and is not consistent with the facts. " She

didn't elaborate on that point, but went on to say " GSK abided by all

regulatory requirements for submitting safety data. We also

communicated safety and efficacy data to physicians through posters,

abstracts, and other publications. "

 

Study 329 was eventually published (J Am Acad Child Adolesc Psychiatry

2001;40[7]:762-72) in 2001. The authors concluded that paroxetine

is " generally well tolerated and effective for major depression in

adolescents. " Among the 93 adolescents taking Seroxat, there were 5

serious cases of " emotional lability " (e.g., suicidal ideation/

gestures). Among the 95 patients taking the comparison treatment,

imipramine (Tofranil), there was 1 such case, and among the 89

subjects receiving placebo there was also 1. According to the

article, only 1 serious adverse event — headache in 1 patient — was

considered by the treating investigator to be related to paroxetine

treatment.

 

Britain's Medicines and Healthcare products Regulatory Authority

(MHRA) advised doctors in June 2003 that paroxetine should not be

prescribed to patients under the age of 18 because evidence from

various clinical trials showed that episodes of suicidal behaviour

were between 1.5 and 3.2 times higher in children taking the drug

than in those receiving placebo. Several nations, including the US,

France and Ireland, quickly followed suit. The MHRA subsequently

reviewed and banned the pediatric use of 6 other SSRIs (exempting

fluoxetine [Prozac]) and is now reviewing their use among adults.

 

The US Food and Drug Administration is now reviewing pediatric trials

of 8 antidepressants. It's been estimated that as many as 11 million

American, and 3 million Canadian children are taking

antidepressants. — Wayne Kondro, Ottawa, and Barbara Sibbald, CMAJ

 

© 2004 Canadian Medical Association or its licensors

 

~~~~~~~~~~~~~

GlaxoSmithKline Net Falls 16% On Soft Paxil Sales, Legal Costs

Revenue Declines 5.1% As Generic Products Hurt Sales of

Antidepressant By SUSANNAH RODGERS DOW JONES NEWSWIRES

 

LONDON -- GlaxoSmithKline PLC said its net income fell 16% in the

fourth quarter, hurt by previously announced legal costs related to

its anti-inflammatory product Relafen, and weaker sales of the

antidepressant Paxil. The London drug maker reported net income of

£790 million ($1.47 billion or €1.16 billion), compared with £935

million in the fourth quarter of 2002. Revenue fell 5.1% to £5.38

billion from £5.67 billion, the company said.

 

For the full year, net profit rose 4.3% to £4.8 billion, or 77.2

pence a share, from £4.6 billion, or 66.2 pence a share. Sales edged

up to £21.4 billion from £21.2 billion. GlaxoSmithKline reports

financial results in British pounds but generates most of its sales

in the U.S., the world's largest pharmaceutical market.

 

" We had to absorb a number of hits, " Chief Executive Jean-Pierre

Garnier said, including generic competition to antidepressant Paxil

and legal costs of £228 million in the latest quarter. " We lost 40%

of our Paxil sales within weeks. There were also legal costs and

restructuring charges, and the continuing adverse impact of the U.S.

dollar exchange rate, " he said. " We've been able to grow despite this

bad news because we have 10 major products growing in double digits, "

Mr. Garnier added. Among them are diabetes treatment Avandia and

asthma drug Seretide. Peter Cartwright, an analyst at Williams de

Broe, said the legal costs, which resulted from litigation over a

patent on one of Glaxo's older drugs, distorted the final numbers.

Mr. Garnier said Glaxo will make several drug launches in 2004,

including the first once-daily treatment for HIV to be available in a

single tablet.

 

As to whether the company will step in as a friendly bidder for

Franco-German pharmaceutical company Aventis SA as it tries to

prevent a hostile takeover by Sanofi-Synthelabo SA, Mr. Garnier

declined to say whether Aventis had approached Glaxo.

 

" In terms of our strategy, we're completely focused on organic

growth. Our first priority is to grow the pipeline, " he said. " You

can never close the door completely on any kind of transaction, but

we're very aware that it would be distracting to make a large-scale

merger, " he said. In London trading Thursday, Glaxo shares closed

down 3.7% at £11.30

 

Separately, Glaxo disclosed that it has been subpoenaed this month by

the U.S. Attorney's Office in Colorado in an investigation of the

marketing and promotion of several of its best-selling products " for

the period from January 1997 to present. " Glaxo said it is

cooperating with the investigation, which is in its " early stages. "

The company didn't offer any other information about the nature of

the investigation.

 

Several drug companies have come under scrutiny in the U.S. for their

marketing practices. Investigations of other companies have involved

the alleged improper inflation of prices and the promotion of drugs

for uses that haven't been approved by regulators. Write to Susannah

Rodgers at susannah.rodgers Updated February 13, 2004

2:44 a.m.

 

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