Merck & Co.

Merck & Co., Inc. (nyse: MRK), dba Merck Sharp & Dohme, MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. Merck headquarters is located in Whitehouse Station, New Jersey. The company was established in 1891 as the United States subsidiary of the German company now known as Merck KGaA. Merck & Co. was confiscated by the US government during World War I and subsequently established as an independent American company. It is currently one of the world's seven largest pharmaceutical companies by market capitalization and revenue.

The company describes itself as "a global research-driven pharmaceutical company" that "discovers, develops, manufactures and markets a broad range of innovative products to improve human and animal health, directly and through its joint ventures".

Merck also 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 textbook, and the Merck Index, a compendium of chemical compounds.

In 2011 the company received the "Facility of the Year"-Award for the integration of its global clinical supplies manufacturing, packing, and warehouse building in Summit, New Jersey, USA.

History
Merck & Co. traces its origins to Friedrich Jacob Merck, who purchased a drug store in Darmstadt, Germany, in 1668, and also to Emanuel Merck, who took over the store several generations later in 1816. Emanuel and his successors gradually built up a chemical-pharmaceutical factory that produced raw materials for pharmaceutical and other preparations.

In 1891, George Merck emigrated to the United States and set up Merck & Co. in New York as the US arm of the family partnership, E. Merck (named for Emanuel Merck), which is now Merck KGaA. In keeping with a national wartime policy, Merck & Co. was confiscated 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 rights to the name in North America, while its former parent company retains the rights in the rest of the world.

In 1953, Merck merged with Philadelphia-based Sharp & Dohme, Inc., becoming the largest US drugmaker. The merger combined Merck'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 acquired Charles E. Frosst Ltd. of Montreal (founded 1899) and created Merck-Frosst Canada, Inc., as its Canadian subsidiary and pharmaceutical research facility. Merck closed this facility in July 2010, and the company was renamed Merck Canada in 2011.

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.

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

As of November 2009, the US company has about 51,000 employees in 120 countries with 31 factories worldwide. It is one of the world's seven largest pharmaceutical companies, exceeding the size of its German ancestor, which employs 41,000 people in 67 countries, as of March 2011.

The Merck Company Foundation has distributed more than $480 million to educational and non-profit organizations since it was founded in 1957.

Products

 * Antivenin – for the treatment of black widow spider (Latrodectus mactans) bites
 * Arcoxia (etoricoxib) – for the symptomatic treatment of osteoarthritis (not approved in the US, but approved and sold in Europe, Latin America, the Asia-Pacific region and Middle East/Northern Africa)
 * Cancidas (caspofungin) – an echinocandins antifungal drug for treatment of Aspergillus and Candida.
 * Cosopt (dorzolamide and timolol) – reduces intraocular pressure in people with glaucoma or ocular hypertension.
 * Cozaar (losartan) – used to treat hypertension, to reduce the risk of strokes and to treat diabetic nephropathy.
 * Crixivan (indinavir) – a protease inhibitor HIV medication.
 * Emend (aprepitant) – treats vomiting and nausea brought about by chemotherapy.
 * Emend Injection (fosaprepitant dimeglumine) – an intravenous drug for nausea and vomiting caused by chemotherapy
 * Emflex (acemetacin) – a non-steroidal anti-inflammatory drug.
 * Fosamax (alendronate) – osteoporosis medication.
 * Fosamax Plus D (alendronate/vitamin D) – osteoporosis medication.
 * Gardasil (HPV vaccine) – a vaccine against human papillomavirus, a sexually transmitted disease.
 * Hyzaar (losartan/hydrochlorothiazide) – used to treat hypertension, to reduce the risk of strokes and to treat diabetic nephropathy.
 * Isentress (raltegravir) – HIV integrase inhibitor.
 * Janumet (sitagliptin/metformin) – an oral anti-diabetic drug for the treatment of type 2 diabetes.
 * Januvia (sitagliptin) – a dipeptidyl peptidase-4 inhibitor for the treatment of diabetes
 * Maxalt (rizatriptan) – one of many triptans used to treat migraines.
 * M-M-R II (MMR Vaccine) – immunization against measles, mumps and rubella.
 * Pneumovax 23 (Pneumococcal polysaccharide vaccine) – a vaccine used to prevent Streptococcus pneumoniae infections such as pneumonia and septicaemia.
 * Primaxin (imipenem with cilastatin) – a broad spectrum carbapenem antibiotic.
 * Prinzide (lisinopril/hydrochlorothiazide) – anti-hypertensive combination of an ACE inhibitor and a diuretic.
 * Propecia/Proscar (finasteride) – used for alopecia (male pattern baldness) and prostatic conditions.
 * ProQuad (MMRV vaccine) – a vaccine for simultaneous vaccination against measles, mumps, rubella, and varicella in children.
 * Recombivax HB (hepatitis B vaccine) – a vaccine that protects against hepatitis B.
 * Rotateq – a vaccine to prevent rotavirus gastroenteritis, a leading cause of severe diarrhea in infants and young children ages 0 to 12.
 * Singulair (montelukast) – an asthma medication that blocks leukotrienes.
 * Timoptic (timolol) – a non-selective beta-adrenergic receptor blocker used to treat high blood pressure and prevent heart attacks.
 * Tredaptive (laropiprant/ER niacin) – a new lipid-modifying therapy for patients with dyslipidemia and primary hypercholesterolemia (not approved in the US, but approved in the European Union)
 * Trusopt (dorzolamide) – reduces intraocular pressure in people with glaucoma or ocular hypertension.
 * Vaqta (hepatitis A vaccine) – a vaccine that protects against hepatitis A.
 * Varivax (Varicella vaccine) – a vaccine that protects against chickenpox.
 * Vytorin (ezetimibe/simvastatin) – a combination cholesterol-lowering preparation marketed in collaboration with Schering-Plough.
 * Zetia (ezetimibe) – cholesterol absorption inhibitor which lowers LDL co marketed by Schering-Plough
 * Zocor (simvastatin) – a cholesterol-lowering statin.
 * Zolinza (vorinostat) – a histone deacetylase inhibitor for the treatment of cutaneous T cell lymphoma.
 * Zostavax – a vaccine for prevention of shingles in adults older than 50 years of age.

Products from Schering-Plough

 * Remicade
 * Levitra
 * Zetia
 * Vytorin
 * Nasonex
 * Asmanex
 * Claritin
 * Aerius
 * Cerazette
 * Esmeron
 * Zemuron
 * Intron A
 * Livial
 * Marvelon
 * Desogen
 * Noxafil
 * Puregon
 * Follistim
 * Remeron
 * Temodar, Temodal, Temozolomide
 * Bridion
 * Quazepam
 * Afrin
 * NuvaRing
 * Home Again Pet Recovery System
 * Banamine
 * Clarinex
 * Dr. Scholl's
 * Coppertone
 * Famvir
 * A+D Original Ointment
 * A+D Zinc Oxide Cream
 * Bain de Soleil
 * Coricidin
 * Correctol
 * Drixoral
 * Zinka
 * Tinactin
 * Lotrimin
 * Gyne-Lotrimin
 * MiraLAX
 * Polaramine

Products under development

 * Anacetrapib
 * Deforolimus
 * Odanacatib
 * Rolofylline
 * Telcagepant
 * An antidote for statin toxicity involving CoQ10 (which has been held for over 20 years without producing it)

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. Currently, Merck & Co. offers 7 patient assistance programs, each with specific eligibility requirements.

Available programs

 * Act Program For Emend
 * Emend (aprepitant)
 * ACT Program For Zolinza
 * Zolinza (vorinostat)
 * Merck Anti-Infective Hotline
 * Cancidas (caspofungin)
 * Invanz (ertapenem)
 * Primaxin (imipenem with cilastatin)
 * Merck Patient Assistance Program
 * Cosopt (dorzolamide and timolol)
 * Cozaar/Hyzaar (losartan)
 * Fosamax (alendronate
 * Fosamax Plus D (alendronate/vitamin D)
 * Janumet (sitagliptin/metformin)
 * Januvia (sitagliptin)
 * Maxalt (rizatriptan)
 * Singulair (montelukast)
 * Timoptic (timolol)
 * Trusopt (dorzolamide)
 * Merck Prescription Discount Program
 * Cosopt (dorzolamide and timolol)
 * Cozaar/Hyzaar (losartan)
 * Emend (aprepitant)
 * Fosamax (alendronate
 * Fosamax Plus D (alendronate/vitamin D)
 * Indocin (Indometacin)
 * Janumet (metformin)
 * Januvia (sitagliptin)
 * Maxalt (rizatriptan)
 * Singulair (montelukast)
 * Timoptic (timolol)
 * Trusopt (dorzolamide)
 * Merck Vaccine Patient Assistance Program
 * Gardasil (HPV vaccine)
 * MMR Vaccine
 * Pneumovax 23 (Pneumococcal polysaccharide vaccine)
 * Recombivax HB (hepatitis B vaccine)
 * Vaqta (Hepatitis A vaccine)
 * Varivax (Varicella vaccine)
 * Zostavax
 * SUPPORT Program For Crixivan
 * Crixivan (indinavir)

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 stronger than existing medications, while easier on the stomach than established anti-inflammatory drugs such as naproxen. Vioxx became one of the most prescribed drugs in history. According to internal e-mail traffic released at a later lawsuit, Merck had a list of doctors critical of Vioxx to be "neutralised" or "discredited." "We may need to seek them out and destroy them where they live," wrote an employee. Also alleged were intimidation of researchers and impingement upon academic freedom.

Thereafter, studies by Merck and by others found an increased risk of heart attack associated with Vioxx use when compared with naproxen. There was no indication of this risk in the original placebo-controlled safety trials, and it was possible that the effect was more related to naproxen decreasing the risk of heart attacks than one of Vioxx increasing the risk. 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. 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. The FDA has since recommended that Vioxx be put back on the market, but with a more prominent warning regarding cardiovascular risks on its label.

On November 5, 2004 the medical journal The Lancet published the results of its analysis of the available studies. It concluded that "the unacceptable cardiovascular risks of Vioxx (rofecoxib) were evident as early as 2000..." The journal's editors criticized Merck for having kept the drug on the market as long as it did before withdrawing it, and also criticized the FDA for its failure of regulatory oversight.

About 50,000 people have sued Merck claiming that they or their family members have suffered medical problems such as heart attacks or strokes after taking Vioxx. In 2005, Merck was found liable in the first case that went to trial and the plaintiff was awarded $253.4 million in damages; however, the judgement was subsequently reduced to $20 million and then, upon appeal, the verdict was reversed in 2008. In November 2007, Merck proposed to pay $4.85 billion to settle most of the pending Vioxx lawsuits. The settlement will require that claimants provide medical proof of having suffered a heart attack or a stroke and show they received at least 30 Vioxx pills. This proposed settlement is generally viewed by industry analysts and investors as a victory for Merck, considering that original estimates of Merck's liability reached as high as $50 billion. As of mid-2008, plaintiffs have prevailed in only three of the twenty cases that have reached juries, all with relatively small awards.

On May 20, 2008, Merck was found liable for using deceptive marketing tactics to promote Vioxx and 30 states will split the $58 million settlement. The amount is the largest multi-state settlement against a pharmaceutical company. All its new television pain-advertisements must be vetted by the Food and Drug Administration and changed or delayed upon request until 2018.

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" 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. 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, 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. This donation program can be touted as the longest ongoing drug donation program of its kind and is used as a case study in corporate ethics today.

Currently, more than 700 million people have been treated since the inception of the program with a staggering 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.

Cordaptive
On September 4, 2007, Merck & Co. introduced the experimental drug Cordaptive, which can both raise HDL and lower LDL (combining an extended-release form of the B vitamin niacin with laropiprant, a novel compound intended to inhibit flushing or redness of the face). Cordaptive caused 18% drop in levels of LDL-C00, a 26% drop in triglycerides, and a 20% increase in HDL-C. Merck's cholesterol statin drug Zocor has seen sales plunge since its patent expired in 2006. In addition, Merck and partner Schering-Plough Corp. jointly market two other cholesterol drugs, Zetia and Vytorin.

On April 24, 2008, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of the combination, to be marketed in Europe as Tredaptive.

On April 28, 2008, the FDA issued a "not approvable" letter for Cordaptive. In the FDA's letter, the agency rejected the proposed trade name CORDAPTIVE for MK-0524A.

The drug was later approved by the EMA on July 3, 2008.

Phony medical journal
From 2002 through 2005 the Australian affiliate of Merck sponsored the eight issues of a medical journal, the Australasian Journal of Bone and Joint Medicine, published by Elsevier. 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. In 2009, the CEO of Elsevier's Health Sciences Division, Michael Hansen, admitted that the practice was "unacceptable".

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. They alleged that Merck failed to pay proper rebates to Medicaid and other health care programs and paid illegal remuneration to health care providers. 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, and 49 states and Washington, DC, over $290 million. One whistleblower received a $68 million reward. Merck made the settlement without an admission of liability or wrongdoing.

Environmental record
Merck & Co. once used methylene chloride, an animal carcinogen on the United States Environmental Protection Agency's list of pollutants, as an ingredient in some of its pharmaceuticals. 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.

In 1991, Merck's Kelco subsidiary was responsible for 1/3 of the volatile organic compound (VOC) emission pollution in the San Diego area. Ground level ozone was causing lung tissue damage by exposure to harmful bacteria.

In 1996 Merck paid $1.8 million for polluting the air. New machines were installed to reduce smog emissions by 680000 lb a year.

Isentress
Raltegravir (Isentress), Merck's HIV integrase inhibitor was unanimously recommended for accelerated approval by the FDA's Advisory Committee on September 5, 2007. Isentress works by acting on a specific enzyme in HIV, integrase, that allows the RNA from HIV to become part of human DNA in the replication process. Isentress was approved by the FDA on October 12, 2007.

Singulair
The FDA is looking into a link between Merck's Singulair and suicide and is considering further studies of the drug. Singulair blocks the leukotriene pathway in asthma and allergic rhinitis.

Propecia
Merck is currently being sued over failing to warn patients of persistent sexual dysfunction, loss of libido,  severe depression,  cognitive impairment, Peyronie’s disease, penile shrinkage and gynecomastia from Propecia. In July 2012, the Post Finasteride Syndrome Foundation was formed to help victims of Propecia.