GlaxoSmithKline

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GlaxoSmithKline
Public limited company
Traded as LSE: GSK
NYSE: GSK
Industry Pharmaceutical
Biotechnology
Consumer goods
Predecessor Glaxo plc
Wellcome plc
Beecham Group plc
Kline & French
Beckman Companies
Smith plc
Founded 2000; 15 years ago (2000)
Headquarters Brentford, London, United Kingdom
Key people
Products Pharmaceuticals, vaccines, oral healthcare products, nutritional products, over-the-counter medicines
Revenue £23.006 billion (2014)[1]
£3.597 billion (2014)[1]
£2.831 billion (2014)[1]
Number of employees
 96,575 (2015)[2]
Subsidiaries Stiefel Laboratories
Slogan "Do more, feel better, live longer"
Website www.gsk.com
Footnotes / references
Key people (Chairman)[3]

GlaxoSmithKline plc (GSK) is a British multinational pharmaceutical company headquartered in Brentford, London. It was the world's sixth-largest pharmaceutical company in 2014, after Pfizer, Novartis, Sanofi, Hoffmann-La Roche and Merck.[4] It was established in 2000 by a merger of Glaxo Wellcome (formed from Glaxo's 1995 acquisition of Burroughs Wellcome) and SmithKline Beecham (from the 1989 merger of the Beecham Group and the SmithKline Beckman Corporation).

The company has a primary listing on the London Stock Exchange and is a constituent of the FTSE 100 Index. As of 6 May 2015 it had a market capitalisation of £73 billion, the fourth-largest of any company listed on the London Stock Exchange.[5] It has a secondary listing on the New York Stock Exchange. Andrew Witty has been the chief executive officer since May 2008.[6]

GSK has a portfolio of products for major disease areas such as asthma, cancer, infections, mental health, diabetes and digestive conditions. Its drugs and vaccines earned £21.3 billion in 2013; its top-selling products that year were Advair, Avodart, Flovent, Augmentin, Lovaza and Lamictal. The company applied for regulatory approval in 2014 for the first malaria vaccine, RTS,S, which it plans to make available for five percent above cost.[7] Legacy products developed at GSK include albendazole for parasitic infections; amoxicillin, amoxicillin-clavulanate, mupriocin, and trimethoprim for bacterial infections; allopurinol for gout; mercaptopurine and thioguanine for cancer; pyrimethamine for malaria, ranitidine for gastroesophagael reflux disease, and zidovudine for HIV infection, all listed in the World Health Organization Model List of Essential Medicines

GSK's consumer healthcare products, which earned £5.2 billion in 2013, include Sensodyne and Aquafresh toothpaste, the malted-milk drink Horlicks, Abreva for cold sores, Breathe Right nasal strips, Nicoderm and Nicorette nicotine replacements, and Night Nurse, a cold remedy.[8]

In 2012 GSK pleaded guilty to criminal charges in the United States, and agreed to pay a $3 billion (£1.9bn) settlement, including a criminal fine of $1 billion. It was the largest health-care fraud case to date in that country and the largest settlement by a drug company. The charges related to GSK's promotion of drugs for unapproved uses, including the anti-depressants Paxil and Wellbutrin, failure to report safety data about the diabetes drug Avandia, reporting false prices to Medicaid, and kickbacks to physicians.[9] The company announced in 2013 that it would no longer pay physicians to promote its drugs or attend medical conferences, and would abolish prescription targets for its sales staff.[10]

History[edit]

Glaxo Wellcome[edit]

The historic Glaxo factory in Bunnythorpe, New Zealand, with the Glaxo Laboratories sign still visible

Glaxo was founded in the 1850s as a general trading company in Bunnythorpe, New Zealand, by a Londoner, Joseph Nathan.[11] In 1904 it began producing dried-milk baby food, first known as Defiance, then as Glaxo, under the slogan "Glaxo builds bonny babies".[12][13] The Glaxo Laboratories sign is still visible (right) on what is now a car repair shop on the main street of Bunnythorpe.

Glaxo Laboratories opened new units in London in 1935. The company bought two companies, Joseph Nathan and Allen & Hanburys in 1947 and 1958 respectively. After the company bought Meyer Laboratories in 1978, it began to play an important role in the US market. In 1983 the American arm, Glaxo Inc., moved to Research Triangle Park (US headquarters/research) and Zebulon (US manufacturing) in North Carolina.[13]

Burroughs Wellcome & Company was founded in 1880 in London by the American pharmacists Henry Wellcome and Silas Burroughs. The Wellcome Tropical Research Laboratories opened in 1902. In 1959 the Wellcome Company bought Cooper, McDougall & Robertson Inc. to become more active in animal health.[13] Glaxo and Burroughs Wellcome merged in 1995 to form Glaxo Wellcome.[14] Glaxo restructured its R&D operation that year, cutting 10,000 jobs worldwide, closing its R&D facility in Beckenham, Kent, and opening a Medicines Research Centre in Stevenage, Hertfordshire.[15][16][17] Also that year, Glaxo Wellcome acquired the California-based Affymax, a leader in the field of combinatorial chemistry.[18]

By 1999 Glaxo Wellcome had become the world's third-largest pharmaceutical company by revenues (behind Novartis and Merck), with a global market share of around 4 per cent.[19] Its products included Imigran (for the treatment of migraine), salbutamol (Ventolin) (for the treatment of asthma), Zovirax (for the treatment of coldsores), and Retrovir and Epivir (for the treatment of AIDS). In 1999 the company was the world's largest manufacturer of drugs for the treatment of asthma and HIV/AIDS.[20] It employed 59,000 people, including 13,400 in the UK, had 76 operating companies and 50 manufacturing facilities worldwide, and seven of its products were among the world's top 50 best-selling pharmaceuticals. The company had R&D facilities in Hertfordshire, Kent and London, and manufacturing plants in Scotland and the north of England. It had R&D centres in the US and Japan, and production facilities in the US, Europe and the Far East.[21]

SmithKline Beecham[edit]

Beecham's Clock Tower, constructed 1877, part of the Beecham's factory, St Helens

In 1843 Thomas Beecham launched his Beecham's Pills laxative in England, giving birth to the Beecham Group. Beecham opened its first factory in St Helens, Lancashire, England, for rapid production of medicines in 1859. By the 1960s Beecham was extensively involved in pharmaceuticals.[13]

In 1830 John K. Smith opened its first pharmacy in Philadelphia. In 1865 Mahlon Kline joined the business, which 10 years later became Smith, Kline & Co. In 1891 it merged with French, Richard and Company, and in 1929 changed its name to Smith Kline & French Laboratories as it focused more on research. Years later it bought Norden Laboratories, a business doing research into animal health, and Recherche et Industrie Thérapeutiques in Belgium in 1963 to focus on vaccines. The company began to expand globally, buying seven laboratories in Canada and the US in 1969, and in 1982 bought Allergan, a manufacturer of eye and skincare products.[13]

SmithKline & French merged with Beckman Inc. in 1982 and changed its name to SmithKline Beckman. In 1988 it bought its biggest competitor, International Clinical Laboratories, and in 1989 merged with Beecham to form SmithKline Beecham plc. The headquarters moved from the US to England. To expand R&D in the US, the company bought a new research center in 1995; another opened in 1997 at New Frontiers Science Park, Harlow, England.[13]

GlaxoSmithKline[edit]

Glaxo Wellcome and SmithKline Beecham announced their intention to merge in January 2000. The merger was completed in December that year, forming GlaxoSmithKline (GSK).[22][23] The company's global headquarters are at GSK House, Brentford, London, officially opened in 2002 by then-Prime Minister Tony Blair. The building was erected at a cost of £300 million, and as of 2002 was home to 3,000 administrative staff.[24] Andrew Witty took over as CEO in May 2008. Witty joined Glaxo in 1985, and had been president of GSK's Pharmaceuticals Europe since 2003.[25] Chris Gent, former CEO of Vodaphone, has been the chair since January 2005.[26] Philip Hampton, chair of the Royal Bank of Scotland, will replace Gent in September 2015.[27]

Facilities[edit]

Corporate information
GlaxoSmithKline headquaters -Brentford, London, England-2Oct2011.jpg
GSK House, Brentford, London

Portals:

As of 2013 GSK had offices in over 115 countries and employed over 99,000 people, 12,500 in R&D. The company's single largest market is the United States. Its US headquarters are in The Navy Yard, Philadelphia, and Research Triangle Park, North Carolina; its consumer-products division is in Moon Township, Pennsylvania.[28]:7[29] Company facilities include:

Products[edit]

Further information: List of GlaxoSmithKline products

GSK manufactures products for major disease areas such as asthma, cancer, infections, diabetes and mental health. Its biggest-selling in 2013 were Advair, Avodart, Flovent, Augmentin, Lovaza, and Lamictal; its drugs and vaccines earned £21.3 billion that year. Other top-selling products include its asthma/COPD inhalers Advair, Ventolin, and Flovent; its diphtheria/tetanus/pertussis vaccine Infanrix and its hepatitis B vaccine; the antihyperlipedemia drug Lovaza; and the antibacterial Augmentin.[28]:220

Medicines historically discovered or developed at GSK and its legacy companies and now sold as generics include amoxicillin[30] and amoxicillin-clavulanate,[31] ticarcillin-clavulanate,[32] mupirocin,[33] and ceftazidime[34] for bacterial infections, zidovudine for HIV infection, valacyclovir for herpes virus infections, albendazole for parasitic infections, sumatriptan for migraine, lamotrigine for epilepsy, bupropion and paroxetine for major depressive disorder, cimetidine and ranitidine for gastroesophageal reflux disorder, mercaptopurine[35] and thioguanine[36] for the treatment of leukemia, allopurinol for gout,[37] pyrimethamine for malaria,[38] and the antibacterial trimethoprim.[36] Among these, albendazole, amoxicillin, amoxicillin-clavulanate, allopurinol, mercaptopurine, mupriocin, pyrimethamine, ranitidine, thioguanine, trimethoprim and zidovudine are listed on the World Health Organization's list of essential medications.[39]

GSK's consumer healthcare division, which earned £5.2 billion in 2013, sells oral healthcare, including Aquafresh, Maclean's and Sensodyne toothpastes; and drinks such as Horlicks, Boost, a chocolate-flavoured malt drink sold in India, and formerly Lucozade and Ribena, sold in 2013 to Suntory for £1.35bn.[40] Other products include Abreva to treat cold sores; Night Nurse, a cold remedy; Breathe Right nasal strips; and Nicoderm and Nicorette nicotine replacements.[41]

Operations and acquisitions[edit]

2001–2010[edit]

photograph
Andrew Witty, GSK's CEO since May 2008

GSK completed the acquisition of New Jersey-based Block Drug in 2001 for US$1.24 billion.[42] In 2006 GSK acquired the US-based consumer healthcare company CNS Inc., whose products included Breathe Right nasal strips and FiberChoice dietary supplements, for US$566 million in cash.[43] GSK opened its first R&D centre in China in 2007, in Shanghai, initially focused on neurodegenerative diseases.[44]

In 2009 GSK acquired Stiefel Laboratories, then the world's largest independent dermatology drug company, for US$3.6bn.[45] In November the FDA approved GSK's vaccine for 2009 H1N1 influenza protection, manufactured by the company's ID Biomedical Corp in Canada.[46] Also in November 2009 GSK formed a joint venture with Pfizer to create ViiV Healthcare, which specializes in HIV research.[47] In 2010 the company acquired Laboratorios Phoenix, an Argentine pharmaceutical company, for US$253m,[48] and the UK-based sports nutrition company Maxinutrition for £162 million (US$256 million).[49]

2011–present[edit]

In 2011, in a $660-million deal, Prestige Brands Holdings took over 17 GSK brands with sales of $210 million, including BC Powder, Beano, Ecotrin, Fiber Choice, Goody's Powder, Sominex and Tagamet.[50] In 2012 the company announced that it would invest £500 million in manufacturing facilities in Ulverston, northern England, designating it as the site for a previously announced biotech plant.[51] In May that year it acquired CellZome, a German biotech company, for US$98 million,[52] and in June worldwide rights to alitretinoin (Toctino), an eczema drug, for $302 million.[53] In 2013 GSK acquired Human Genome Sciences (HGS) for $3 billion; the companies had collaborated on developing the lupus drug Belimumab (Benlysta), albiglutide for type 2 diabetes, and darapladib for atherosclerosis.[54]

In 2014 GSK paid $1 billion to raise its stake in its Indian pharmaceutical unit, GlaxoSmithKline Pharmaceuticals, to 75 percent as part of a move to focus on emerging markets.[55] Also that month it recalled Alli, an over-the-counter weight-loss drug, in the US and Puerto Rico because of possible tampering, following customer complaints.[56] In April Novartis and Glaxo agreed on more than $20 billion in deals, with Novartis selling its vaccine business to GSK and buying GSK's cancer business.[57][58] In February 2015 GSK announced that it would acquire GlycoVaxyn, a Swiss pharmaceutical company, for $190 million.[59] In June 2015, the company announced it would sell two meningitis drugs to Pfizer, Nimenrix and Mencevax, for around $130 million.[60]

Acquisition history[edit]

The following is an illustration of the company's major mergers and acquisitions and historical predecessors (this is not a comprehensive list):

GlaxoSmithKline
SmithKline Beecham plc
(renamed 1989)
SmithKline Beckman
(renamed 1982)
SmithKline-RIT
(renamed 1968)
Smith, Kline & French
(reorganized 1929 into
Smith Kline and French Laboratories)

French, Richards and Company
(Acq 1891)


Smith, Kline and Company
(Founded 1830)




Recherche et Industrie Thérapeutiques
(Acq 1968)



Beckman Instruments, Inc.
(Merged 1982, Sold 1989)

Specialized Instruments Corp.
(Acq 1954)


Offner Electronics
(Acq 1961)




Allergan
(Acq 1982, Sold 1989)


International Clinical Laboratories
(Acq 1989)



Beecham Group Plc
(merged 1989)

Norcliff Thayer
(Acq 1986)

Beecham Group Ltd

S. E. Massengill Company
(Acq 1971)

Beecham Group Ltd
(Renamed 1945)

C.L. Bencard
(Acq 1953)



County Chemicals
(Acq 1929)






Glaxo Wellcome
(Renamed 1995)
Glaxo
(Merged 1995)




Glaxo
(Founded 1850)


Joseph Nathan
(Acq 1947)



Allen & Hanburys
(Founded 1715, Acq 1958)



Meyer Laboratories
(Acq 1978)



Affymax
(Acq 1995)


Burroughs Wellcome
(Merged 1995)

McDougall & Robertson Inc
(Acq 1959)


Burroughs Wellcome & Company
(Founded 1880)




Philanthropy and social responsibility[edit]

Developing world health issues[edit]

GlaxoSmithKline, Center City, Philadelphia

Access to Medicines Index[edit]

Since 2010 GlaxoSmithKline has several times ranked first among pharmaceutical companies on the Global Access to Medicines Index, which is funded by the Bill and Melinda Gates Foundation.[61]

Global Alliance to Eliminate Lymphatic Filariasis[edit]

GSK has been active, with the World Health Organization (WHO), in the Global Alliance to Eliminate Lymphatic Filariasis (GAELF). Around 120 million people globally are believed to be infected with lymphatic filariasis.[62] In 2012 the company endorsed the London Declaration on Neglected Tropical Diseases, a collaborative disease eradication programme. Under this agreement GSK committed to donating 400 million albendazole tablets to the WHO each year to fight soil-transmitted helminthiasis, and to continue to provide 600 million albendazole tablets every year for lymphatic filariasis until the disease is eradicated.[63] As of 2014, over 5 billion treatments have been delivered and 18 of 73 countries in which the disease is considered endemic have progressed to the surveillance stage based on a preliminary assessment that the infection has been eliminated.[64]

Medicines Patent Pool[edit]

In 2009 the company said it would cut drug prices by 25 percent in 50 of the poorest nations, release intellectual property rights for substances and processes relevant to neglected disease into a patent pool to encourage new drug development, and invest 20 percent of profits from the least-developed countries in medical infrastructure for those countries.[65][66] Médecins Sans Frontières welcomed the decision, but criticized GSK for failing to include HIV patents in its patent pool, and for not including middle-income countries in the initiative.[67]

In 2013, GSK licensed its HIV portfolio to the Medicines Patent Pool for use in children, and agreed to negotiate a license for dolutegravir, an integrase inhibitor then in clinical development.[68] In 2014, this license was extended to include dolutegravir and adults with HIV. The licenses include countries in which 93% of adults and 99% of children with HIV live.[69]

Malaria vaccine development[edit]

In 2014 GSK applied for regulatory approval for the first malaria vaccine.[70] Known as RTS,S, the vaccine was developed as a joint project with the PATH vaccines initiative and the Bill and Melinda Gates Foundation. The company has committed to making the vaccine available in developing countries for five percent above the cost of production.[7] Malaria is responsible for over 650,000 deaths per year, mainly in Africa.[71] As of 2013 RTS,S, which uses GSK's proprietary AS01 adjuvant, was being examined in a Phase 3 trial in eight African countries. PATH reported that "[i]n the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5-17 months, and approximately 30% protection in children aged 6-12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines."[72] In 2014 Glaxo said it had spent more than $350 million, and expected to spend an additional $260 million before seeking regulatory approval.[73][74]

A second generation malaria vaccine is currently being evaluated in Phase 2 clinical trials.[75]

Other[edit]

In 2014 the Human Rights Campaign, an LGBT-rights advocacy group gave GSK a score of 100% in its Corporate Equality Index.[76]

Political activity[edit]

In 2013 GlaxoSmithKline spent between €600,000 and €650,000 lobbying European Union institutions and $3,720,000 on federal lobbying activities in the United States. Additional indirect expenditures were made through membership in national and international trade organizations. The company does not directly contribute to the political candidates, but in 2013 U.S. members of the GSK employee political action committee contributed $484,810 to political campaigns in the United States. Approximately 60% of this amount was donated to Republican candidates and 40% to Democrats.[77]

Scientific Recognition[edit]

Four GlaxoSmithKline scientists have been recognized by the Nobel Committee for their contributions to basic medical science and/or therapeutics development.

  • Henry Dale, a former student of Paul Ehrlich, received the 1936 Nobel Prize in Medicine for his work on the chemical transmission of neural impulses. Dale served as a pharmacologist and then as Director of the Wellcome Physiological Research Laboratories from 1904 to 1914, and later served as Trustee and Chairman of the Board of the Wellcome Trust.[78]
  • John Vane of Wellcome Research Laboratories shared the 1982 Nobel Prize for Medicine for his work on prostaglandin biology and the discovery of prostacyclin. Vane served as Group Research and Development Director for The Wellcome Foundation from 1973 to 1985.[79]
  • Gertrude B. Elion and George Hitchings, both of the Wellcome Research Laboratories, shared the 1988 Nobel Prize in Medicine with Sir James W. Black ""for their discoveries of important principles for drug treatment"." Elliot and Hitchings were responsible for the discovery of a plethora of important drugs, including mercaptopurine[35] and thioguanine[36] for the treatment of leukemia, the immunosuppressant azothioprine,[80] allopurinol for gout,[37] pyrimethamine for malaria,[38] the antibacterial trimethoprim,[36] acyclovir for herpes virus infection,[81] and nelarabine for cancer treatment.[82]

2012 criminal and civil settlement[edit]

Overview[edit]

In July 2012 GSK pleaded guilty in the United States to criminal charges, and agreed to pay $3 billion, in what was the largest settlement until then between the Justice Department and a drug company. The $3 billion included a criminal fine of $956,814,400 and forfeiture of $43,185,600. The remaining $2 billion covered a civil settlement with the government under the False Claims Act. The investigation was launched largely on the basis of information from four whistleblowers who filed qui tam (whistleblower) lawsuits against the company under the False Claims Act.[9]

The charges stemmed from GSK's promotion of the anti-depressants Paxil (paroxetine) and Wellbutrin (bupropion) for unapproved uses from 1998–2003, specifically as suitable for patients under the age of 18, and from its failure to report safety data about Avandia (rosiglitazone), both in violation of the Federal Food, Drug, and Cosmetic Act. Other drugs promoted for unapproved uses were two inhalers, Advair (fluticasone/salmeterol) and Flovent (fluticasone propionate), as well as Zofran (ondansetron), Imitrex (sumatriptan), Lotronex (alosetron) and Valtrex (valaciclovir).[9]

The settlement also covered reporting false best prices and underpaying rebates owed under the Medicaid Drug Rebate Program, and kickbacks to physicians to prescribe GSK's drugs. There were all-expenses-paid spa treatments and hunting trips for doctors and their spouses, speakers' fees at conferences, and payment for articles ghostwritten by the company and placed by physicians in medical journals.[9] The company set up a ghostwriting programme called CASPPER, initially to produce articles about Paxil but which was extended to cover Avandia.[83]

As part of the settlement GSK signed a five-year Corporate Integrity Agreement with the Department of Health and Human Services, which obliged the company to make major changes in the way it did business, including changing its compensation programmes for its sales force and executives, and to implement and maintain transparency in its research practices and publication policies.[9] It announced in 2013 that it would no longer pay doctors to promote its drugs or attend medical conferences, and that its sales staff would no longer have prescription targets.[10]

Rosiglitazone (Avandia)[edit]

Further information: Rosiglitazone § Adverse effects and Rosiglitazone § Lawsuits
Rosiglitazone

The 2012 settlement included a criminal fine of $242,612,800 for failing to report safety data to the FDA about Avandia (rosiglitazone), a diabetes drug approved in 1999, and a civil settlement of $657 million for making false claims about it. The Justice Department said GSK had promoted rosiglitazone to physicians with misleading information, including that it conferred cardiovascular benefits despite an FDA-mandated label warning of cardiovascular risks.[84]

In 1999 John Buse, a diabetes specialist, told medical conferences that rosiglitazone might carry an increased risk of cardiovascular problems. GSK persuaded Buse to sign a retraction, after threatening to sue him and calling his university department head.[85] A congressional inquiry reported that GSK had raised questions internally about the drug's safety in 2000, and that in 2002 the company ghostwrote an article in Circulation describing a GSK-funded clinical trial that suggested rosiglitazone might have a beneficial effect on cardiovascular risk.[86] From 2001 reports began to link the thiazolidinediones (the class of drugs to which rosiglitazone belongs) to heart failure.[87] In April that year GSK began a six-year, open-label, randomized trial, known as RECORD, to examine rosiglitazone and cardiovascular events.[88] Two GSK meta-analyses in 2005 and 2006 showed an increased risk of cardiovascular problems with rosiglitazone; the information was passed to the FDA and posted on the company website, but not otherwise published. By December 2006 rosiglitazone had become the top-selling diabetes drug, with annual sales of US$3.3 billion.[87]

In 2007 a meta-analysis by Steven Nissen and Kathy Wolski, published in June in the New England Journal of Medicine, associated the drug with a significant increase in the risk of heart attack.[89] GSK reportedly tried to persuade Nissen not to publish, after receiving an advance copy from one of the journal's peer reviewers, a GSK consultant.[90] In July 2007 FDA scientists suggested that rosiglitazone had caused 83,000 excess heart attacks between 1999 and 2007.[91]:4[92] The FDA placed restrictions on the drug, including adding a boxed warning about heart attacks, but did not withdraw it.[93] (In 2013 the FDA rejected that the drug had caused excess heart attacks.)[94] A two-year inquiry by the Senate Finance Committee concluded in January 2010 that GSK had sought to intimidate several scientists who had concerns about rosiglitazone.[91]:2ff In February that year the company tried to halt publication of an editorial about the controversy by Nissen in the European Heart Journal.[95]

The final results of GSK's RECORD trial were published in June 2009. The study confirmed an association between rosiglitazone and an increased risk of heart failure and fractures, but not of heart attack, and concluded that it "does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs."[88] Nissen and Wolksi criticized the trial's open-label design and argued that its low event rates reduced its statistical power.[96] In September 2009 rosiglitazone was suspended in Europe.[97] The results of the RECORD study were confirmed in 2013 by the Duke Clinical Research Institute, in an independent review required by the FDA.[98] In November that year the FDA lifted the restrictions it had placed on the drug.[99] The boxed warning about heart attack was removed; the warning about heart failure remained in place.[94]

Paroxetine (Paxil/Seroxat), bupropion (Wellbutrin)[edit]

Paroxetine, known as Paxil and Seroxat

GSK paid a criminal fine and forfeiture of $757,387,200 for misbranding Paxil/Seroxat (paroxetine), an SSRI anti-depressant released by GSK in 1992, and Wellbutrin (bupropion), an anti-depressant also used as a smoking-cessation aid, Zyban.[9]

The company promoted Wellbutrin, approved at the time for major depressive disorder, for weight loss and the treatment of attention deficit hyperactivity disorder, sexual dysfunction and substance addiction. GSK paid doctors to promote these off-label uses, and set up supposedly independent advisory boards and Continuing Medical Education programmes.[9]

Paxil had $4.97 billion worldwide sales in 2003.[100] From 2004 its label, along with those of similar drugs, included an FDA-mandated boxed warning that it might increase the risk of suicidal ideation and behaviour in patients under 18.[9] The company conducted nine trials between 1994 and 2002, none of which showed that Paxil helped children with depression.[101] From 1998 to 2003 GSK promoted Paxil for the under-18s, paying for promotional speakers, spas, lunches and dinners.[9]

The company withheld data from clinical trials, and prepared an article that misreported the results of a trial, according to the Justice Department.[9] Known as study 329, the article – which has not been retracted[102] – was published in 2001 in the Journal of the American Academy of Child and Adolescent Psychiatry; it listed 20 authors but had been ghostwritten by GSK. The article concluded that Paxil was "generally well tolerated and effective for major depression in adolescents," although 11 subjects on Paxil, against two on placebo, had experienced serious adverse events during the trial, including emotional lability, suicidal ideation, and behavioral problems. The data behind the article came to light in 2004 during a class-action suit.[103] An internal SmithKline Beecham document said in 1998, about withheld data from two GSK studies: "It would be commercially unacceptable to include a statement that [pediatric] efficacy had not been demonstrated, as this would undermine the profile of paroxetine."[100][104] The suppression of the research findings and the legal discovery process that uncovered it is the subject of Side Effects (2008) by Alison Bass.[105]

For 10 years GSK marketed Paxil as non-habit forming. In 2001 35 patients filed a class-action suit alleging they had suffered withdrawal symptoms, and in 2002 a Los Angeles court issued an injunction preventing GSK from advertising that the drug was not habit forming.[106] The court subsequently withdrew the injunction[107] after the FDA directly, and through an amicus brief filed by the Department of Justice, objected that the court had no jurisdiction over drug marketing that the FDA had approved.[108] In 2003 a World Health Organization committee reported that Paxil was among the top 30 drugs, and top three antidepressants, for which dependence had been reported. The committee "agreed that withdrawal was indeed a problem in some patients, but there was a difference of opinion on the degree of dependence that was involved."[109]

Other controversies[edit]

Antitrust case over griseofulvin[edit]

In the 1960s Glaxo Group Ltd. (Glaxo) and Imperial Chemical Industries (ICI) each owned patents covering various aspects of the antifungal drug griseofulvin.[110]:54, nn. 1–2[111] They created a patent pool by cross-licensing their patents, subject to express licensing restrictions that the chemical from which the "finished" form of the drug (tablets and capsules) was made must not be resold in bulk form, and they licensed other drug companies to sell the drug in finished form and subject to similar restrictions.[110]:54–55[111] The effect and intent of the bulk-sale restriction was to keep the drug chemical out of the hands of small companies that might act as price-cutters, and the effect was to maintain stable, uniform prices.[112][113][114]

The United States brought an antitrust suit against the two companies, charging them with violation of the Sherman Act and also seeking to have the patents declared invalid.[110]:55[111] The trial court found that the defendants had engaged in several unlawful conspiracies, but dismissed the part of the suit seeking invalidation of patents and refused to grant as relief mandatory sales of the bulk drug chemical and compulsory licensing of the patents.[110]:56[111] The government appealed to the Supreme Court, which reversed, in United States v. Glaxo Group Ltd., 410 U.S. 52 (1973).[111]

In 1973 the Supreme Court held that (1) when a patent is directly involved in an antitrust violation, the Government may challenge the validity of the patent; and (2) ordinarily, in patent-antitrust cases, "[m]andatory selling on specified terms and compulsory patent licensing at reasonable charges are recognized antitrust remedies."[110]:62–64[111][114]

Ribena[edit]

photograph
photograph
Old Ribena bottle, year unknown, made by Beecham Products, Brentford, Middlesex; the label states: "widely used in hospitals and clinics."

There were concerns throughout the 2000s about the sugar and vitamin content of Ribena,[citation needed] a blackcurrant-based syrup and soft drink owned by GSK until 2013. Produced in England by H.W. Carter & Co from the 1930s, the company's unbranded blackcurrant syrup was distributed to children there as a source of vitamin C during World War II, which gave Ribena a reputation with customers in the UK and Commonwealth as good for health. Beecham bought H.W. Carter in 1955.[115]

In 2001 the British Advertising Standards Authority (ASA) required GSK to withdraw its claim that Ribena Toothkind, a syrup with less sugar than regular Ribena, did not encourage tooth decay. A company poster showed bottles of Toothkind in place of the bristles on a toothbrush. The ASA's ruling was upheld by the High Court. The British Dental Association described Ribena ToothKind as "a soft drink dentists can recommend with confidence". A spokesperson for the association said that Toothkind was accredited three years ago "because oral health would improve if children drank this sort of product instead of conventional sugary and acidic drinks".[116]

In 2007 GSK pleaded guilty to 15 charges in New Zealand over its claim that ready-to-drink Ribena, sold already diluted in cartons, contained high levels of vitamin C. The country's Commerce Commission found that it contained no detectable vitamin C, and the company was fined $217,000.[117][118] In 2013 GSK sold Ribena and Lucozade, another drink, to the Japanese multinational Suntory for £1.35 billion.[40]

SB Pharmco Puerto Rico[edit]

In 2010 the US Department of Justice announced that GSK would pay a $150 million criminal fine and forfeiture, and a civil settlement of $600 million under the False Claims Act. The fines stemmed from production of improperly made and adulterated drugs from 2001 to 2005 at GSK's subsidiary, SB Pharmco Puerto Rico Inc., in Cidra, Puerto Rico, which at the time produced $5.5 billion of products each year. The drugs involved were Kytril, an antiemetic; Bactroban, used to treat skin infections; Paxil, the anti-depressant; and Avandamet, a diabetes drug.[119] GSK closed the factory in 2009.[120]

According to the New York Times, the case began in 2002 when GSK sent experts to fix problems cited by the FDA. The lead inspector recommended recalls of defective products, but they were not authorized; she was fired in 2003 and filed a whistleblower lawsuit. In 2005 federal marshals seized $2 billion worth of products, the largest such seizure in history. In the 2010 settlement SB Pharmco pleaded guilty to criminal charges, and agreed to pay $150 million in a criminal fine and forfeiture, at that time the largest such payment ever by a manufacturer of adulterated drugs, and $600 million in civil penalties to settle the civil lawsuit.[120]

China[edit]

In 2013 Chinese authorities announced that GSK had funnelled HK$3.8 billion since 2007 in kickbacks to GSK managers, doctors, hospitals and others who prescribed their drugs, using over 700 travel agencies and consulting firms.[121] Chinese authorities arrested four GSK executives as part of a four-month investigation into claims that doctors were bribed with cash and sexual favours.[122] In 2014 a Chinese court found the company guilty of bribery, imposed a fine of $490 million. Mark Reilly, the British head of GSK's Chinese operations, received a three-year suspended prison sentence after a one-day trial held in secret.[123] Reilly was reportedly deported from China and dismissed by the company.[124]

Miscellaneous[edit]

Italian police sought bribery charges in May 2004 against 4,400 doctors and 273 GSK employees. GSK and its predecessor were accused of having spent £152m on physicians, pharmacists and others, giving them cameras, computers, holidays and cash. Doctors were alleged to have received cash based on the number of patients they treated with a cancer drug, topotecan (Hycamtin).[125] The following month prosecutors in Munich accused 70–100 doctors of having accepted bribes from SmithKline Beecham between 1997 and 1999. The inquiry was opened over allegations that the company had given over 4,000 hospital doctors money and free trips.[126] All charges were dismissed by the Verona court in January 2009.[127]

In 2006 in the United States GSK settled the largest tax dispute in IRS history, agreeing to pay $3.1 billion. At issue were Zantac and other products sold in 1989–2005. The case revolved around intracompany transfer pricing—determining the share of profit attributable to the US subsidiaries of GSK and subject to tax by the IRS.[128]

The UK's Serious Fraud Office (SFO) opened a criminal inquiry in 2014 into GSK's sales practices, using powers granted by the Bribery Act 2010.[129] The SFO said it was collaborating with Chinese authorities to investigate bringing charges in the UK related to GSK's activities in China, Europe and the Middle East.[130] Also as of 2014 the US Department of Justice was investigating GSK with reference to the Foreign Corrupt Practices Act.[131]

See also[edit]

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References[edit]

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  113. ^ The Court explained: "There is little reason to think that the appellees or their licensees, now that the bulk-sales restrictions have been declared illegal, will begin selling in bulk. It is in their economic self-interest to maintain control of the bulk form of the drug in order to keep the dosage-form, wholesale market competition-free. Bulk sales would create new competition among wholesalers, by enabling other companies to convert the bulk drug into dosage and microsize forms and sell to retail outlets, and would presumably lead to price reductions as the result of normal competitive forces. There is, in fact, substantial evidence in the record to the effect that other drug companies would not only have entered the market, had they been able to make bulk purchases, but also would have charged substantially lower wholesale prices." United States v. Glaxo Group Ltd. at 62-63.
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  117. ^ David Eames (28 March 2007). "Judge orders Ribena to fess up". The New Zealand Herald. 
  118. ^ Tony Jaques, "When an Icon Stumbles – The Ribena Issue Mismanaged, Corporate Communications: An International Journal, 13(4), 2008, pp. 394–406.
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  121. ^ Alice Yan and Toh Han Shih (16 July 2013). "Shanghai travel agent's revenue surge led to arrests in GSK bribery case". South China Morning Post. 

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  122. ^ Rupert Neate and Angela Monaghan, "GlaxoSmithKline admits some staff in China involved in bribery", The Guardian, 22 July 2013.

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  123. ^ "China Fines GlaxoSmithKline Nearly $500 Million in Bribery Case - The New York Times". 
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  125. ^ John Hooper, Heather Stewart, "Over 4,000 doctors face charges in Italian drugs scandal", The Guardian, 27 May 2004.
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  128. ^ "GlaxoSmithKline to Settle Tax Dispute With U.S.", Reuters, 12 September 2006; "IRS Accepts Settlement Offer in Largest Transfer Pricing Dispute", IRS, 11 September 2006.
  129. ^ Julia Kollewe (28 May 2014). "GlaxoSmithKline faces criminal investigation by Serious Fraud Office". The Guardian. 
  130. ^ Kirsten Ridley, "UK fraud office liaising with China on GSK bribery case", Reuters, 23 July 2014.
  131. ^ "GlaxoSmithKline faces bribery claims in Syria", Reuters, 12 August 2014.

External links[edit]

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