MERCK APPEARS TO HAVE KNOWN OF DANGER EARLIER THAN THOUGHT.
Merck & Co., Inc., knew of problems with its blockbuster painkiller Vioxx long before the drug was pulled from the market in September due to newer studies that linked the medication to an increased risk of heart attack and stroke, the Wall Street Journal reported Monday.
The newspaper cited internal company e-mails, marketing materials, and interviews with outside scientists. It said as early as the mid-to-late 1990s, the company worried that Vioxx's heart risk appeared to be much greater than that of older, cheaper painkillers that had a reputation for being tougher on the stomach, the Journal reported. See full story at http://www.healthcentral.com/news/NewsFullText.cfm?id=1505142.
December 1998
Food and Drug Administration approves Pfizer Inc.'s Celebrex, the first Cox-2 inhibitor, to treat arthritis. Cox-2 drugs, part of the nonsteroidal anti-inflammatory (NSAID) drug class, inhibit the Cox-2 enzyme, which promotes inflammation, but protect users against stomach bleeds and ulcers, unlike other NSAIDS.
May 1999
FDA approves Merck & Co.'s Vioxx, another Cox-2 inhibitor, for treatment of arthritis and acute pain in adults.
June 2000
Merck gives FDA results of VIGOR study, which shows Vioxx users suffered five times as many heart attacks as users of the older painkiller naproxen, sold under the brand name Aleve. Merck attributes the disparity to naproxen's cardioprotective qualities rather than a defect in Vioxx, garnering a rebuke from the FDA for making that assertion without scientific proof.
September 2001
Merck receives a warning letter from the FDA about the company's post-VIGOR Vioxx promotional campaign "that minimizes the potentially serious cardiovascular findings" and "misrepresents the safety profile of Vioxx."
November 2001
Pfizer's Bextra, also a Cox-2 inhibitor, is approved by FDA.
April 2002
FDA changes warning label on Vioxx to reflect VIGOR study results showing increased risk of heart attacks and strokes.
May 2002
Carol Ernst sues Merck, alleging Vioxx triggered the May 2001 death of her husband, Robert Ernst, a 59-year-old Wal-Mart produce manager who ran marathons.
September, 2004
Merck stops long-term APPROVe study, saying it showed Vioxx could double risk of heart attack or stroke if taken for 18 months or longer. APPROVe had focused on whether Vioxx could prevent reoccurrence of colon polyps, and on cardiovascular effects. Merck then voluntarily withdraws Vioxx from the market.
October 1, 2004
MERCK FORCED TO TAKE ACTION. Merck only took Vioxx off the market after an outside panel of experts overseeing a clinical trial of Vioxx told the company "to halt the trial and immediately stop patients from taking the drug." Wall Street Journal, October 1, 2004. "The decision to withdraw Vioxx was based on data from a big three-year clinical trial" which concluded that "people who took Vioxx for more than 18 months were twice as likely to have a heart attack or stroke during the study." Wall Street Journal, October 1, 2004.
SHORT TERM USE DANGEROUS. A joint study by the Kaiser
Permanente Medical Foundation and the FDA reported a tripling of heart
attack risk among patients who took double the standard 25 mg. dose. Dr.
David Campen, a Santa Clara rheumatologist who led the study for Kaiser,
said "the higher risk for heart attack was spotted among patients who
were just starting on Vioxx, as well as those who had taken it
for long periods of time."
San Francisco Chronicle, October 1, 2004.
October 2, 2004
RISK GREATER FOR THOSE WITH HEART CONDITIONS. Dr. Topol warned that the risk of heart attack "may be greatly underestimated" because "Merck's trial did not include anyone with known heart disease - patients who might be expected to have the highest risk." New York Times, October 2, 2004.
MERCK'S CONFLICT OF INTEREST. Dr. Topol said that "despite studies showing the magnitude of the public health problem, for several years Merck did nothing to investigate. This surely represents a conflict between the interests of the public and the interests of the company. Instead of doing the requisite research in patients with heart disease - who frequently have arthritis as well and are thus prime users of anti-inflammatory medicines - the company undertook studies that avoided them. At the same time Merck spent at least $100 million a year for direct-to-consumer Vioxx advertising, while the company's employees and their consultants published several papers in medical journals rebutting studies reporting Vioxx's heart attack risk." New York Times, October 2, 2004.
October 6, 2004
FDA STUDY ESTIMATES VIOXX LINKED TO 27,000 HEART ATTACKS.
A study led by a Food and Drug Administration safety official projects
that the widespread use of Vioxx may have led to more than 27,000 heart
attacks and sudden cardiac deaths before the drug's abrupt withdrawal
last week by Merck & Co. (MRK), according to an October 6, 2004 Wall
Street Journal report.
CNN Money, October 6, 2004.
February 2005
FDA panel concludes Vioxx, Celebrex and Bextra all pose heart risks, but should be available to consumers.
April 7, 2005
Pfizer withdraws Bextra from the market at request of the FDA, which said it carries additional risks of serious, sometimes fatal skin reactions. The FDA also says not just Cox-2 inhibitors, but all prescription NSAID drugs, should carry a black-box warning label about cardiovascular risks.
July 13, 2005
A jury of seven men and five women is seated to hear the Ernst Vioxx lawsuit in semi-rural Brazoria County, south of Houston.
July 19, 2005
U.S. District Judge Eldon Fallon schedules the first federal Vioxx trial for Nov. 28.
Aug. 19, 2005
Texas jury finds Merck liable or the death of Robert Ernst, awarding his widow $253.4 million in damages. That will be reduced to about $26 million under Texas caps on punitive damages; Merck plans to appeal.
Sept. 14, 2005
The second Vioxx trial begins with opening arguments in New Jersey Superior Court in Atlantic City, as lawyers for Boise, Idaho postal worker Frederick "Mike" Humeston argue his Sept. 18, 2001, heart attack was caused by Vioxx, which he had been taking for about two months.
Oct. 24, 2005
In its quarterly earnings report, Merck says that as of Sept. 30, it has been named as a defendant in about 6,400 lawsuits over Vioxx -- about 160 of them potential class-action suits -- and has signed agreements with about 3,000 other claimants temporarily suspending the clock on their states' time limit to file suit. At least several hundred additional lawsuits are filed in October.
Nov. 3, 2005
Atlantic County Superior Court jury rules Merck & Co. not responsible for Humeston's heart attack.
Dec. 8, 2005
An editorial in the New England Journal of Medicine said Merck concealed heart attacks suffered by three patients during a clinical study of Vioxx in a report on the study published in the journal in 2000.
Dec. 12, 2005
Merck emerges from its third Vioxx trial with a hung jury when the panel failed, in about 18 hours of deliberations over three days, to side with the drug maker or the widow of a 53-year-old Florida man who died after taking Vioxx for about a month.
Jan. 23, 2006
Jury selection begins in the fourth Vioxx trial in Rio Grande City, Texas, considered by legal experts as one of the most plaintiff-friendly regions in the country. The jury will be deciding if 71-year-old Leonel Garza's fatal 2001 heart attack was caused by 23 years of heart disease or by about three weeks of taking Merck & Co.'s Vioxx for arm pain.
Feb. 17, 2006
A federal jury clears Merck & Co. of any responsibility in the death of a 53-year-old Florida man who had a heart attack after taking its once popular painkiller Vioxx for less than a month.
April 5, 2006
A jury in Atlantic City, N.J., finds Merck liable for New Jersey resident John McDarby’s nonfatal heart attack, but not for one suffered by fellow plaintiff Thomas Cona. The jury ordered that McDarby receive $4.5 million in compensatory damages; the panel said Cona should get $45
August 17, 2006
New Orleans Jury Rules Against Merck
A federal jury ruled that drug manufacturer Merck failed to warn doctors about the medical risks of its painkiller Vioxx, which was taken off the market in September 2004. The jury ruled that the company must pay a retired F.B.I. agent who suffered a heart attack while taking the drug at least $50 million in damages. Merck still faces some 14,000 lawsuits over Vioxx, involving about 27,000 plaintiffs, in federal and state courts.