Vioxx Controversy

Romain Floyd, Suki Fuller, Andrea Villanera, Michele Barone, Steven Smith

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”

Major Players

• Raymond Gilmartin: Former CEO

• Edward Scolnick: Former President Merck Research Laboratories

• Cardiologist: Dr. Eric Topol

• Victim: Newton Acker (no picture)

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

Pipeline

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• Withdrawn April 7, 2005 • Increase risk of heart attack, stroke, and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

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®

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

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

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

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

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

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

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

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

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

Vioxx® and Merck

• Merck’s Reputation– Talented scientists– Renown research facilities – Arrogance– Self-righteous

• FDA – Speedy approvals– Organizational favoritism– Lackluster policy

Vioxx and Industry

• Vioxx® Recall

• Industry Competition– Pfizer

• Industry Reaction and Effects

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

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”

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

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

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

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”

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)

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

Closing Statement / Questions

Questions?

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

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.

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