Merck & Co.

Not to be confused with the Merck Group (Merck KGaA), its original parent company which owns the rights to the name "Merck" in 191 of 193 countries.
Merck & Co., Inc.
Public
Traded as
Industry Pharmaceuticals
Founded 1891 as a subsidiary of Merck (founded 1668)
1917 as an independent company
Founders George Merck
Headquarters Kenilworth, New Jersey, United States
Key people
Kenneth Frazier
(Chairman, President and CEO)
Products Gardasil
Singulair
Propecia/Proscar
Zocor Vioxx Fosamax Keytruda Januvia Primaxin
Revenue Decrease US$39.498 billion (2015)[1]
Decrease US$6.928 billion (2015)[1]
Decrease US$4.442 billion (2015)[1]
Total assets Decrease US$98.335 billion (2015)[1]
Total equity Decrease US$48.647 billion (2015)[1]
Number of employees
70,000 (2015)[1]
Website Merck.com

Merck & Co., Inc. (NYSE: MRK), d.b.a. Merck Sharp & Dohme (MSD) outside the United States and Canada, is an American pharmaceutical company and one of the largest pharmaceutical companies in the world.

The company was established in 1891 as the United States subsidiary of the German company Merck, which was founded in 1668 by the Merck family. Merck & Co. was nationalized by the US government during World War I and subsequently established as an independent American company in 1917. While it operates as Merck & Co. in North America, the original Merck based in Darmstadt holds the rights to the Merck name everywhere else. Merck & Co. is the world's seventh largest pharmaceutical company by market capitalization and revenue. Its headquarters is located in Kenilworth, New Jersey.[2]

Merck & Co. publishes The Merck Manuals, a series of medical reference books for physicians, nurses, and technicians. These include the Merck Manual of Diagnosis and Therapy, the world's best-selling medical reference. The Merck Index, a compendium of chemical compounds, was formerly published by Merck & Co. before being acquired by the Royal Society of Chemistry in 2012.

Company history

Early history and roots

The Angel Pharmacy in Darmstadt, the beginning of the Merck company

Merck & Co. traces its origins to its original German parent company Merck, which was established by the Merck family in 1668 when Jacob Friedrich Merck purchased a drug store in Darmstadt. In the 19th century, the Merck company in Darmstadt evolved from a pharmacy to a major pharmaceutical company which pioneered the commercial manufacture of morphine.

In 1891, family member George (Georg) Merck emigrated to the United States and set up Merck & Co. in New York as the US subsidiary of the family company. Merck & Co. was nationalized by the US government in 1917 and re-established as an independent American company. Until the end of World War II, the company was led by George W. Merck. Merck & Co. hold the trademark rights to the "Merck" name in North America, while its former parent company retains the rights in the rest of the world.[3]

In 1929, H. K. Mulford Company merged with Sharpe and Dohme, Inc. This company brought to the future Merck & Co, Inc vaccine technology, including immunization of cavalry horses in World War I and delivery of a diphtheria antitoxin in 1925.[4]

1950 to 2000

In 1953, Merck & Co. merged with Philadelphia-based Sharp & Dohme, Inc., founded by Alpheus Phineas Sharp and Carl Friedrich Louis Dohme in 1845, becoming the largest US drugmaker.[5][6] The merger combined Merck & Co.'s strength in scientific research and chemical manufacturing with Sharp & Dohme's sales and distribution system and its marketing expertise. The combined company kept the trade name Merck in the United States and Canada, and as Merck Sharp & Dohme (MSD) outside North America. In 1965 Merck & Co. acquired Charles E. Frosst Ltd. of Montreal, Canada (founded 1899) and created Merck-Frosst Canada, Inc., as its Canadian subsidiary and pharmaceutical research facility. Merck & Co. closed this facility in July 2010,[7] and the company was renamed Merck Canada in 2011.

The company was incorporated in New Jersey in 1970.[8] It has an operating subsidiary, KBI Inc., which was originally formed as a joint venture with AstraZeneca.[8] In November 1993, Merck & Co. completed a $6 billion purchase of Medco Containment Services Inc., one of the largest mail-order pharmacy and managed-care drug companies.[9] Merck & Co. spun Medco off ten years later, and on August 20, 2003, Medco Health Solutions began trading on the New York Stock Exchange.[10] (In 2012, Medco merged with, and became a wholly owned subsidiary of, Express Scripts Holding Co.)[11]

2001 to present

In November 2009, Merck & Co. announced that it would merge with competitor Schering-Plough in a US$41 billion deal.[12][13][14][15] Although Merck & Co. was in reality acquiring Schering-Plough, the purchase was structured on paper as a "reverse merger", in which "Old" Merck & Co. was renamed Merck Sharpe & Dohme, and Schering-Plough renamed as "Merck & Co., Inc." so that it could, technically, continue as the surviving public corporation.[16] The maneuver was an attempt to preserve Schering-Plough's rights to market Remicade, which was ultimately decided by arbitration.[17] The merger was completed on 2009-11-04. As of 2015, Merck Sharp & Dohme remains a subsidiary of the Merck & Co. parent.[18]

As of December 2013, the US company had approximately 76,000 employees in 120 countries with 31 factories worldwide. It is one of the world's seven largest pharmaceutical companies. The Merck Company Foundation has distributed more than $480 million to educational and non-profit organizations since it was founded in 1957 (and $740 million in overall charitable distributions).[19][20] On December 7, 2012, the foundation announced that it was ending its donations to the Boy Scouts of America because of "its policy that excludes members on the basis of sexual orientation", which "directly conflicts with the Merck Foundation's giving guidelines."[21] In October 2013, Merck & Co. announced it would cut 8,500 jobs in an attempt to cut $2.5bn (£1.5bn) from its costs by 2015. The company's shares rose 2.35% to US$48.73 in New York trading after it announced the cuts. The new losses, combined with 7,500 job cuts announced in 2011 and 2012, amount in total to 20% of its workforce.[22]

In June 2014 Merck & Co. announced its acquisition of Idenix Pharmaceuticals for approximately US$3,850,000,000.[23] In December 2014 Merck & Co. announced they would be spending US$8,400,000,000 to buy Cubist Pharmaceuticals.[24] Later in the same month the company acquired the Swiss biotechnology company OncoEthix for up to US$375,000,000 dependent upon certain milestone achievements.[25]

In July 2015 Merck & Co. and Ablynx expanded their 18 month old immuno-oncology collaboration by four years, generating a potential $4.4 billion in milestone payments for the Abylnx.[26] Days later Merck & Co. announced it would spend $95 million up front on collaborating with cCAM Biotherapeutics and its lead candidate (an early-stage treatment similar to Keytruda). The company is due up to $510 million more, which is tied to clinical, regulatory and commercial milestones. Merck & Co. will bring in CM-24, an antibody designed to block the immune checkpoint CEACAM1.[27]

In January 2016 Merck & Co. announced two new partnerships; the first with Quartet Medicine and its small molecule pain treatments,[28] the second with Complix investigating intracellular cancer targets,[29] with both collaborations potentially generating up to $595 million and $280 million respectively. Days later the company announced it would acquire IOmet Pharma, with IOmet becoming a wholly owned subsidiary of Merck & Co. The acquisition includes IOmets IDO (indoleamine-2,3-dioxygenase 1), TDO (Tryptophan 2,3-dioxygenase), and dual-acting inhibitors.[30] In June, the company announced its acquisition of Afferent Pharmaceuticals for $1.25 billion, gaining Afferents lead compound - AF-219 - used to block P2X3 receptors.[31]

In 191 of 193 countries the original Merck company, the Merck Group of Darmstadt, owns the rights to the "Merck" name. In the United States and Canada the company trades under the name EMD (an abbreviation of Emanuel Merck, Darmstadt). In the United States and Canada Merck & Co. holds the rights to the trademark "Merck", while in the rest of the world the company trades under the name MSD (an abbreviation of Merck, Sharp & Dohme).

In 2015 the Merck Group adopted a new logo and said it will be "much more aggressive" about protecting the brand of "the real Merck."[32] Merck of Darmstadt has initiated litigation against its former subsidiary, Merck & Co. (MSD) of Kenilworth, in several countries over infringing use of the Merck name. In 2016, the High Court of Justice in the United Kingdom ruled that MSD had breached an agreement with its former parent company and that only Merck of Darmstadt is entitled to use the Merck name in the United Kingdom.[33] The judge also held that MSD's use of "Merck" as part of branding on its global websites were directed to the UK and infringed Merck's trade mark rights in the UK.[34]

In response to the ruling, MSD initiated counter-litigation in the United States in January 2016 by filing a federal lawsuit which accused its former parent company of "infringing on its trademark" through actions that included the increased usage of “Merck KGaA” and “MERCK” in branding in the US as well as on its social media presence. Further Merck & Co. has also accused the Merck Group of federal trademark dilution, unfair competition, false advertising, deceptive trade practices, breach of contract, and cybersquatting. The case came to a head when a research scientist believed he was communicating with Merck & Co regarding a research grant in oncology, when in fact they were talking with the Merck Group. As a result, Merck & Co. asked the federal court to stop the Merck Group from using “Merck” on any products or marketing materials in the United States. As a direct result, Merck & Co is seeking “all monetary gains, profits, and advantages” made by the Merck Group and three-times the damage, plus additional punitive damages.[35]

Acquisition history

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

Merck & Co.













Merck & Co.
(Founded 1891 as a subsidiary of Merck of Darmstadt.
Nationalized by the U.S. government in 1917)






H. K. Mulford Company
(Acq 1929)






Sharp & Dohme, Inc
(Acq 1953)






Charles E. Frosst Ltd
(Acq 1965, restructured into Merck-Frosst Canada, Inc,
restructured into Merck Canada 2011)






Medco Containment Services Inc
(Acq 1993, Spun off 2003)






Schering-Plough
(Acq 2009)




Nobilon




Diosynth




Intervet




Organon International


Schering-Plough

Plough, Inc
(Merged 1971, Founded 1908)



Schering Corporation
(Merged 1971, Founded 1851)











Idenix Pharmaceuticals
(Acq 2014)






Cubist Pharmaceuticals
(Acq 2014)




Trius Therapeutics
(Acq 2013)




Optimer Pharmaceuticals
(Acq 2013) Adolor








OncoEthix
(Acq 2015)






IOmet Pharma
(Acq 2016)






Afferent Pharmaceuticals
(Acq 2016)





On August 17th 2016, Merck & Co was reported to be interested in buying U.S. cancer drug company Medivation Inc.[36]

Corporate governance

In 2005, CEO Raymond Gilmartin retired following Merck's voluntary worldwide withdrawal of Vioxx. Former president of manufacturing Richard Clark was named CEO and company president. Clark retired in October 2011 and Kenneth Frazier became CEO.[37]

On April 23, 2014, Robert M. Davis, formerly CFO of Baxter International, became Merck's CFO.[38] Davis replaced Peter N. Kellogg, who held the post from 2007.[38]

Products

Gardasil

Current

As of August 2014, Merck's research and development effort has led to the approval of more new drugs than that of any other company. Research performed at Merck has led to U.S. FDA approval of 63 New Molecular Entities.[39] In 2014, Merck's major products included[40]

Other products

Legacy products

Vaccines

Medically important vaccines developed at Merck include the first mumps vaccine,[52] the first rubella vaccine,[53] and the first trivalent measles, mumps, rubella (MMR vaccine),[54] each of which was developed by Merck scientist Maurice Hilleman. The incidence of rubella-associated birth defects fell from up to 10,000 per year in the U.S. to zero in the aftermath of the rubella vaccine's development.[55] Hilleman also developed the first Hepatitis B vaccine[56] and the first varicella vaccine, for chickenpox.[57]

Thiazide anti-hypertensives

The thiazide diuretics were discovered developed by scientists Karl H. Beyer, James M. Sprague, John E. Baer, and Frederick C. Novello of Merck and Co. in the 1950s,[58] and led to the marketing of the first drug of this class, chlorothiazide, under the trade name Duiril in 1958.[59] The research leading to the discovery of chlorothiazide, leading to "the saving of untold thousands of lives and the alleviation of the suffering of millions of victims of hypertension" was recognized by a special Public Health Award from the Lasker Foundation in 1975.[60]

First statin

Merck scientists also developed lovastatin, the first drug of the statin class.[61] It was marketed under the trade name Mevacor.

Antibacterials

Streptomycin, discovered during a Merck-funded research program in Selman Waksman's laboratory at Rutgers in 1943, became the first effective treatment for tuberculosis. At the time of its discovery, sanitoriums for the isolation of tuberculosis-infected people were a ubiquitous feature of cities in developed countries, with 50% dying within 5 years of admission.[62])[63] Although Merck's agreement with Rutgers gave it exclusive rights to streptomycin, at Wakman's request the company renegotiated the agreement, returning the rights to the university in exchange for a royalty. The university then set up non-exclusive licenses with seven companies to ensure a reliable supply of the antibiotic.[64]

In 1985 Merck received approval for imipenem, the first member of the carbapenem class of antibiotics. Antibiotics of the carbapenem class play an important role in treatment guidelines for certain hospital-acquired and multi-drug resistant infections.[65][66]

Vioxx

In 1999, the U.S. Food and Drug Administration (FDA) approved Vioxx (known generically as rofecoxib), a Merck product for treating arthritis. Vioxx was designed as a selective inhibitor of the enzyme cyclooxygenase-2. Such compounds were expected to cause less gastrointestinal bleeding than older anti-inflammatory drugs such as naproxen, which were associated with 20,000 hospitalizations and 2000 deaths each year.[67]Vioxx became one of the most prescribed drugs in history.

Thereafter, studies by Merck and by others found an increased risk of heart attack associated with Vioxx use when compared with naproxen. Merck adjusted the labeling of Vioxx to reflect possible cardiovascular risks in 2002.

On September 23, 2004, Merck received information about results from a clinical trial it was conducting that included findings of increased risk of heart attacks among Vioxx users who had been using the medication for over eighteen months.[68] On September 28, 2004, Merck notified the FDA that it was voluntarily withdrawing Vioxx from the market, and it publicly announced the withdrawal on September 30. An analysis for the period 1999-2004, based on U.S. Medical Expenditure Survey data, reported that Vioxx was associated with 46,783 heart attacks, and along with the other popular COX-2 inhibitor Celebrex, an estimated 26,603 deaths from both.[69]

About 50,000 people sued Merck, claiming they or their family members had suffered medical problems such as heart attacks or strokes after taking Vioxx.[70] In November 2007, Merck agreed to pay $4.85 billion to settle most of the pending Vioxx lawsuits.[71] The settlement required that claimants provide medical and pharmacy records confirming the occurrence of a heart attack, ischemic stroke, or sudden cardiac death; the receipt of at least 30 Vioxx pills within 60 days prior to the injury or death; and confirmation of Vioxx being used within 14 days of the Vioxx-related event.[72] The settlement was generally viewed by industry analysts and investors as a victory for Merck, considering that original estimates of Merck's liability reached between $10 billion and $25 billion.[71] In fact, as of mid-2008, when the plaintiff class had reached the threshold percentage required by Merck to go through with the settlement, plaintiffs had prevailed in only three of the twenty cases that had reached juries, all with relatively small awards.[70]

According to internal e-mail traffic released at a later lawsuit, Merck had a list of doctors critical of Vioxx to be "neutralized" or "discredited." "We may need to seek them out and destroy them where they live," wrote an employee. A Stanford Medical School professor said that Merck was engaged in intimidation of researchers and infringement upon academic freedom.[73]

On May 20, 2008, Merck settled for $58 million with 30 states alleging that Merck engaged in deceptive marketing tactics to promote Vioxx.[74] All its new television pain-advertisements must be vetted by the Food and Drug Administration and changed or delayed upon request until 2018.[75]

Mectizan

In 1987, Merck & Co. began a program with UNICEF to donate its new drug Mectizan to "all that need it for as long as needed"[76] in an effort to combat Onchocerciasis, also known as river blindness, primarily in Africa. Up to that point, the World Health Organization had fought the disease through the use of insecticides to lower the population of its primary vector, the Black Fly.[77] However, when studies in the 1980s showed how effective the drug was at treating and preventing the disease, the WHO agreed to use it instead of its previous strategies. Merck's involvement is considered a key factor in the success against the disease all over the world,[78] and the decision to donate the entirety of the drug to all those in need of it is used as part of the Mectizan Donation Program that covers countries such as Yemen and in African countries.[79]

More than 700 million people have been treated since the inception of the program with 80 million people still undergoing treatment in Africa, Latin America, and Yemen. Blindness caused by onchocerciasis is decreasing and there are regions of Latin America and Africa that have been shown to have completely eliminated the disease altogether.[79]

Fosamax

Fosamax (alendronate) is a bisphosphonate used for the treatment of post-menopausal osteoporosis and for the prevention of skeletal problems in certain cancers. The American College of Clinical Endocrinology, the American College of Obstetricians and Gynecologists, the North American Menopause Society and the UK National Osteoporosis Guideline Group recommend alendronate and certain other bisphosphonates as first line treatments for post-menopausal osteopotosis.[80][81][82][83] Long-term treatment with bisphosponates produces anti-fracture and bone mineral density effects that persist for 3–5 years after an initial 3–5 years of treatment.[84] Alendronate reduces the risk of hip, vertebral, and wrist fractures by 35-39%.[85][86]

In December 2013, Merck agreed to pay a total of $27.7 million to 1,200 plaintiffs in a class action lawsuit alleging that the company's osteoporosis drug had caused them to develop osteonecrosis of the jaw. Prior to the settlement, Merck had prevailed in 3 of 5 so-called bellwether trials. Approximately 4000 cases still await adjudiction or settlement as of August 2014.[87]

Society and culture

Patient assistance programs

Merck & Co. was one of the first American pharmaceutical companies to offer assistance to those unable to afford its medications, beginning a program in the 1950s.[88] Merck & Co. offers seven patient assistance programs, each with specific eligibility requirements.[89][90]

Mass retrenchment

As of January 2015, 30000 people have been forced to leave the company due to economic reasons and Singapore's branch has been the most affected.

Sham medical journal

From 2002 through 2005 the Australian affiliate of Merck paid Elsevier an undisclosed amount to publish eight issues of a medical journal, the Australasian Journal of Bone and Joint Medicine. Although it gave the appearance of being an independent peer-reviewed journal, without any indication that Merck had paid for it, the journal actually reprinted articles that originally appeared in other publications and that were favorable to Merck. The misleading publication came to light in 2009 during a personal injury lawsuit filed over Vioxx; 9 of 29 articles in the journal's second issue referred positively to Vioxx.[91] In 2009, the CEO of Elsevier's Health Sciences Division, Michael Hansen, admitted that the practice was "unacceptable."[92]

Hilleman Laboratories

Merck and the Wellcome trust jointly fund the Hilleman Laboratories, an India-based non-profit research organization dedicated to the development of low cost vaccines for use in developing countries. Current projects include the development of low cost, thermostable vaccines for the prevention of cholera, rotavirus, and meningitis.[93]

Medicaid overbilling

A US Justice Department fraud investigation began in 2000 when allegations were brought in two separate lawsuits filed by whistleblowers under the False Claims Act.[94] They alleged that Merck failed to pay proper rebates to Medicaid and other health care programs and paid illegal remuneration to health care providers.[95] On February 7, 2008 Merck agreed to pay more than $650 million to settle charges that it routinely overbilled Medicaid for its most popular medicines. The settlement was one of the largest pharmaceutical settlements in history. The federal government received more than $360 million, plus 49 states and Washington, DC, received over $290 million. One whistleblower received a $68 million reward.[94][96] Merck made the settlement without an admission of liability or wrongdoing.[97]

Environmental record

Merck & Co. once used methylene chloride, an animal carcinogen on the United States Environmental Protection Agency's list of pollutants, as a solvent in some of its manufacturing processes. Merck chemists and engineers subsequently replaced the compound with others having fewer negative environmental effects. Merck has also modified its equipment to protect the environment, installing a distributed control system that coordinates chemical reactions more efficiently and expedites manufacturing by 50 percent, eliminating the need for the disposal and storage of harmful waste. Biological oxygen demand has also been reduced.[98]

In 1991, Merck's Kelco subsidiary was responsible for volatile organic compound (VOC) emission pollution in the San Diego area. In 1996 Merck paid $1.8 million for polluting the air. New machines were installed to reduce smog emissions by 680,000 lb (310,000 kg) a year.[99]

See also

Notes and references

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