POSTED 13 JAN 2005
Vitiating Vioxx
R
emember
the Pinto? Ford's economy car with the unfortunate tendency to explode
after being rear-ended? Facing monster lawsuits, Ford eventually recalled
and repaired "the bean's" gas tank.
(Pinto courtesy Music
TAP)
Get ready for a druggy deja vu: On Sept. 30, drug maker Merck yanked its highly profitable anti-inflammatory drug Vioxx from
the market. Eighteen months into a test for preventing cancer, those who
got Vioxx had a doubled risk of heart attack and strokes.
That was not the first warning sign for the pain-killer, which reached the market in 1999 and was selling at a $2.5-billion annual clip. Merck was promoting Vioxx, its number-two seller, right up to the withdrawal. The humiliating announcement caused Merck's shares to plunge nearly 27 percent, erasing $28 billion in shareholder value. Hundreds of lawsuits have already begun; early estimates put their price at $12 billion.
Merck
implemented a "voluntary withdrawal," but only extreme circumstances would
cause it to withdraw its number-two product, says Lee Vermeulen, director
of the Center for Drug Policy at the University of Wisconsin-Madison.
"I assure you there would have been FDA [Food and Drug Administration]
action on Vioxx had Merck not acted.2
In an "open letter" written after the withdrawal, Merck CEO Raymond Gilmartin said that the company had gone the extra mile with Vioxx. 3When questions arose, we took additional steps, including conducting further prospective, controlled studies to gain more clinical information about the medicine. When information from these additional prospective, controlled trials became available we acted promptly and made the decision to voluntarily withdraw Vioxx. We believe that a complete review of the facts will demonstrate that Merck1s conduct with respect to Vioxx shows both an ongoing commitment to study Vioxx and prompt and decisive action in response to data from prospective, controlled clinical studies.2
Heart disease usually occurs when cholesterol accumulates
and forms "plaque" in a coronary artery. With blood flow impeded, the
heart becomes starved for oxygen, causing chest pain (angina). If a blood
clot forms and completely blocks the artery, it's called a heart attack,
or myocardial infarction. Image: FDA
Feeling inhibited
Vioxx is a "COX-2 inhibitor," since it blocks the enzyme COX-2, which
plays a role in inflammation, a key source of pain in arthritis. 
Upon
introduction about five years ago, the COX-2 blockers were touted as selective,
laser-like weapons that would be easy on the stomach and intestines. (People
who control pain with the ibuprofens and other pain-relievers may experience
serious, even deadly, bleeding.)
True. But easy on the gut did not mean easy on the heart, and the Vioxx withdrawal triggered a landslide of bad news about COX-2 inhibitors. In December, the FDA halted a large cancer-prevention test of Celebrex, after the 2.5 to 3.4-fold elevation in deaths, heart attacks and strokes shown in the graph on this page. Although Celebrex and Bextra, another COX-2 blocker, remain on the market, Vermeulen says, and the hazard data has not "reached the level we have seen with Vioxx." Still, he says, "I would not be surprised to see a voluntary withdrawal in the next 6 months."
The
Celebrex cancer-prevention trial, which was abruptly halted in December,
caused excess cardiovascular death, heart attack, and stroke. Both doses
were significantly more dangerous than control, but the effects of low
and high doses were statistically the same. Data
from JAMA
What about the human cost of Vioxx? On Nov. 18, David Graham, who is associate director for science in the Office of Drug Safety, whistleblew to Congress that a "more realistic and likely range of estimates for the number of excess cases would be from 88,000 to 138,000" heart attacks or sudden cardiac deaths (click "Dr. Graham's Testimony" here.
To put the death toll in context, Graham suggested that Congress view it as "the rough equivalent of 500 to 900 aircraft dropping from the sky. This translates to two to four aircraft every week, week in and week out, for the past 5 years."
Now, this atrocious toll is an estimate, although an informed one. But as the lawsuits and the bodies both pile up, we wonder how Vioxx got approved, and why it survived five years on the market.
Is the FDA doing its job? Is it too reliant on industry? Is it moving too fast? (Vioxx, after all, was hustled through on a "6-month priority approval," based on that reduction in bleeding.) Is it always possible to catch the side effects of drugs, especially those that might hide among the hundreds of thousands of heart attacks and strokes that "normally" strike Americans each year?
Want the Vioxx story?
Megan Anderson, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive
