This document summarizes the Vioxx controversy involving pharmaceutical company Merck. It describes Merck's development and marketing of the pain medication Vioxx, which was later pulled from the market after studies showed it increased risks of heart attacks and strokes. The summary discusses Merck's aggressive promotion of Vioxx, rejection of proposed safety studies, and eventual $4.85 billion legal settlement after Vioxx was found to have dangerous side effects.

1. Vioxx Controversy Romain Floyd, Suki Fuller, Andrea Villanera, Michele Barone, Steven Smith

2. Merck Merck & Co., Inc. (NYSE: MRK) Hdqtr: Whitehouse Station, NJ Founded:1891 George Merck Chairman, President & CEO: Richard T. Clark Sales: $24.2 billion in 2007 Employees: ~ 59,800 “ Merck Puts Patients First”

3. Major Players Raymond Gilmartin: Former CEO Edward Scolnick: Former President Merck Research Laboratories Cardiologist: Dr. Eric Topol Victim: Newton Acker (no picture)

4. Reputation Stellar High powered Blockbuster drugs Fosamax®, Zetia®, Zocor®, Cozaar® Quick approval by FDA Meticulous Between1995 – 2000 13 major new drugs reviewed and approved in less than eleven months

5. Pipeline

6. Competition to Vioxx® Pfizer (PFE) – only major competition Bextra® (valdecoxib) Withdrawn April 7, 2005 Increase risk of heart attack, stroke, and some fatal skin reaction Recent lawsuits settled October 2008 $894 million Celebrex® (celecoxib) Still marketed claims safe and effective Sales $589 million 3Q08

7. What is Vioxx ® ? Brand name for Merck’s anti-inflammatory drug and pain medication A prescription medicine used to relieve signs and symptoms of arthritis, acute pain in adults, and painful menstrual cycles It is also related to the nonselective NSAIDs, such as ibuprofen, Naproxen®, Celebrex® and Bextra®

8. Description White to off white to light yellow powder tablet Oral administration contains either 12.5 mg, 25 mg or 50 mg Once a popular class of painkillers that generated billions of dollars in annual sales The drugs work by blocking COX-2, an enzyme that inflames the joints

9. Clinical Studies of Vioxx® Significant reduction in joint pain and joint swelling Treatment of the signs and symptoms of Osteoarthritis of the knee and hip

10. Vioxx® Indications and Usage For relief of the signs and symptoms of osteoarthritis For relief of the signs and symptoms of rheumatoid arthritis in adults For relief of the signs and symptoms of pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis in patients 2 years and older and who weighs 10 kg (22 lbs) or more For the management of acute pain in adults For the treatment of primary dysmenorrhea For the acute treatment of migraine attacks with or without aura in adults

11. Vioxx® advantage Provides Once Daily Power in chronic OA The only COX-2 targeted agent that reduced the need for rescue narcotic analgesia Not contraindicated in patients with sulfonamide allergies Demonstrated safety profile in patients 80 years or older Least expensive and branded NSAID

12. Contraindications In patients with known hypersensitivity to component of rofecoxib Should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after aspirin or other NSAIDS Caution should be exercise when Vioxx® is given to patient

13. Warnings Gastrointestinal (GI) Effects Risk of GI Ulceration, bleeding, and perforation. Patients should be informed about the signs and symptoms Anaphylactic Reactions Should not be given to patients with the aspirin triad Advanced Renal Disease Not recommended in patients with advanced renal disease Pregnancy In late pregnancy, Vioxx® should be avoided because it may cause premature closure of the ductus arteriosus Not a substitute for aspirin

14. Sales Incentives Sales reps received $2,000 bonus for attaining 55% and 61% monthly new Rx share of Vioxx® Business managers also earned a bonus for each region that achieved the 55% and/or 61% goals Hospital sales reps also received of $2,000 for attaining 55% and 61% monthly Hospital business managers earned a bonus for each of their territories that achieved the 55% and or 61% goals Creating cardiovascular card

15. Marketing Vioxx® Unusually aggressive Share of Vioxx® in the A & A market is up to 17% and 51.2% in the Coxib® market before the problems erupted. Spent $160 million in advertising Vioxx® alone

16. Vioxx® Dangers Cox-2 Inhibitor Research Merck “Mishandling” -Pre-existing research -Merck funded research -Research findings Vioxx® and the cardio-vascular system Heart attack Stroke Merck’s reaction

17. Vioxx® and Merck Merck’s Reputation Talented scientists Renown research facilities Arrogance Self-righteous FDA Speedy approvals Organizational favoritism Lackluster policy

18. Vioxx and Industry Vioxx® Recall Industry Competition Pfizer Industry Reaction and Effects

19. Industry Analysis Good Life saving therapy Improve quality of life Innovative research and development Bad Perception of greedy multinationals Capitalizing on ills of mankind for a profit Opportune timing in developing and marketing drugs Potential danger to patients Lack of potential ‘blockbusters’ Declining research and development budgets

20. Industry Analysis (continued) “ Promotions targeting physicians account for the majority of drug industry spending on marketing and promotion. In 2003, pharmaceutical companies spent $9 billion on marketing and promotion. Of this amount, $5.7 billion (over 60%) was aimed at physicians. As many as ninety thousand sales representatives meet with physicians about their companies’ products every day”

21. Vioxx® Evaluation Among the first of COX-2 inhibitors Considered one of Merck’s largest products in 2001 Sales of $2.5 billion Dr. Deepak L. Bhatt (cardiologist at the Cleveland Clinic) recommended Merck conduct a study of Vioxx® in patients with severe chest pain. Merck declined March 2000 study indicates “5xs as many patients taking Vioxx® had heart attacks as those taking naproxen” 2002 study examined Vioxx® and other anti-inflammatory drugs interaction with lipids Vioxx® damaged lipids in a way that made them more susceptible to clotting

22. Pulling Vioxx From the Market Four years after May 2000 meeting Merck pulled drug off market in the justification that: Long term clinical trial showed some patients developed serious cardiovascular problems after 18 months 15 cases of heart attack, stroke, or blood clot per 1,000 people

23. Merck Analysis Patents on several popular drugs expired in 2000 and 2001 Increased exposure to generic competition Vioxx® was considered ‘safe until proven otherwise’ Executives rejected cardiovascular study on Vioxx® in 2000 Would have required as many as 50,000 patients Marketers feared this would portray lack a lack of confidence in product Competition from Celebrex® Accused of withholding information on Vioxx® side effects Rushed to be first to market with product and slow to react Aggressive marketing of new drugs

24. Merck Analysis (continued) 3,000 highly trained representatives marketed to doctor’s offices and hospitals with misleading information about Vioxx® risks Marketed Vioxx® 8 to 11 times safer than other anti-inflammatory drugs Omitted VIGOR study Based on data FDA considered to be inappropriate for safety analysis Prohibited representatives from discussing contrary studies Instructed “NOT to initiate discussion on FDA Arthritis Committee” Sales force awarded with thousands of dollars in cash bonuses for meeting sales goals “ A heart attack in exchange for an ulcer is poor treatment ”

25. Future Outlook Vioxx® Lawsuit Damages 50,000 state and federal suits $4.85 billion settlement Damage to reputation Patent Expiration Zocor® – Cholesterol cutting drug (2005) Propecia® – Hair loss drug (2006) Fosamax® – Bone disease drug (2007) Cozaar® – Hyper tension drug (2010)

26. Recent Headlines Merck Cuts 7,200 Jobs (fiercepharma.com) Merck Wrote Drug Studies For Doctors (nytimes) Gardasil® Released – Cervical Cancer Drug FDA Expands Gardasil® Warnings Link to fatalities and Paralysis (washingtontimes) 17 deaths so far Merck Ghost Writes Own Articles

27. Closing Statement / Questions Questions?

28. Sources Smith, Aaron. Zocor and Zoloft face patent expiration . CNNMoney.com 15 June 2006 http://money.cnn.com/2006/06/15/news/companies/zoloft_zocor/index.htm Smith, Aaron. Merck’s Fosamax Get The Ax . CNNMoney.com. 6 Feb 2006 http://money.cnn.com/2008/02/05/news/companies/fosamax/ Fagan, Amy. Merck, FDA expands Gardasil Warning . The Washington Times. 10 July 2008. http://www.washingtontimes.com/news/2008/jul/10/merck-fda-expand-gardasil-warnings/ Death toll linked to Gardasil vaccine rises. WorldNetDaily.com 30 June 2008. http://www.worldnetdaily.com/index.php?fa=PAGE.view&pageId=68454 Bruderlin-Nelson, Christe. Merck To Cut 7,200 Jobs . 22 FiercePharma.com Oct 2008. http://www.fiercepharma.com/story/merck-cut-7-200-jobs/2008-10-22

29. Sources Merck & Co., Inc. http://www.merck.com/product/usa/pi_circulars/v/vioxx/vioxx_pi.pdf . http://www.ssem.com/investigations/vioxx/merck-vioxx-sales.html http://www.fda.gov/CDER/DRUG/infopage/vioxx/vioxx.html . http://oversight .house.gov/features/vioxx/Tab.14.pdf, retrieved 11/07/08.

30. Sources Medical News Today http://www.medicalnewstoday.com/articles/104365.php The New England Journal of Medicine http://content.nejm.org/cgi/content/full/351/17/1707 Merck pipeline http://www.merck.com/finance/pipeline.swf Merck http://www.merck.com/ “ Pfizer Settles Claims Over Celebrex, Bextra” http://online.wsj.com/article/SB122424333713244271.html?mod=googlenews_wsj Phone call: Dr. Steve Chen 11/06/08 Email: Dr. Robert Bresalier 11/6/08