GlaxoSmithKline CEO: "We had to absorb a number of hits"

GlaxoSmithKline CEO: “We had to absorb a number of hits”

Mon, 16 Feb 2004

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 (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/Healy.ppt

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.php

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.php

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.php

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:

~~~~~~~~~~~~~~~~
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.

Updated February 13, 2004 2:44 a.m.

FAIR USE NOTICE: This may contain copyrighted (© ) material the use of which has not always been specifically authorized by the copyright owner. Such material is made available to advance understanding of ecological, political, human rights, economic, democracy, scientific, moral, ethical, and social justice issues, etc. It is believed that this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, this material is distributed without profit to those who have expressed a prior general interest in receiving similar information for research and educational purposes.