Merck, Vioxx - What did they know?

By now, just about everyone has heard about Merck withdrawing its blockbuster arthritis painkiller, Vioxx, because of potential side effects to the heart. Not only has it affected Merck's stock price (plunging 27% or so), it has started a mild panic about other Cox-2 inhibitor drugs. For a good explanation of these drugs, see Derek Lowe's blog In the Pipeline (scroll down to "How Bad are Cox-2 Inhibitors, Anyway?).

Besides the new questions about what Merck knew and what the FDA knew and why that information wasn't made available, in recent months there has been substantial questioning of nearly all major pharma companies about their information practices and policies (including Congressional hearings regarding clinical trial results). This episode adds to the quiet storm of questions about the public trust of the industry, and brings a new dimension to the clinical trial results debates.

It seems a bit much to start crying that the sky is falling in the pharma industry. The public does need, though, to have some assurance that it is getting the information it needs. We and our families all take these drugs and we and our doctors need to be able to make informed decisions. The clinical trial registry is one step to get some of that information, but would not have necessarily brought the current Vioxx problems to light.

I don't think all of the facts have come out about what Merck knew and when and how much they did, if anything, to hide negative data. Unfortunately, more information will likely come to light to make the story even worse.

What concerns me even more are the allegations that the FDA examiners had learned about the problems and took steps to downgrade the language of the warnings. Back in 2001, the director of marketing for the FDA sent a warning letter to Merck stating that its ads downplayed the risk of myocardial infarction and did not do enough to inform physicians of potential cardiovascular risks. It's interesting that this warning was issued, yet reports of the FDA's recent activity seems to show that the FDA examiners took distinct steps (link to WSJ online - subscription required) to minimize the data. It seems that the FDA disagreed with research conducted by Dr. David Graham rofecoxib and memorialized this in emails between Dr. Graham and the FDA. From the article in the Wall St. Journal on Friday, Oct. 8:

Some of the findings became public Aug. 25, when an abstract was presented at a medical conference. On Aug. 12, Anne Trontell, an official in the FDA drug-safety office, wrote in an e-mail to another official that a recommendation about high-dose Vioxx was "unnecessary and particularly problematic" because the FDA funded the study, and that Dr. Graham might be asked to also display "alternative FDA opinion on this."

On Aug. 13, John Jenkins, director of the FDA's office of new drugs, wrote about a proposed conclusion that "this is pretty strong language since to my knowledge FDA is not contemplating such a warning for labeling." He added, "I think something like, 'this and other studies suggest an increased risk of AMI [acute myocardial infarction, or heart attack] with rofecoxib use and should be considered by prescribers when making individual treatment decisions.' "

Huh. So the FDA had sent at least one warning letter to Merck about problems with Merck's toned down information for cardiac problems, but the FDA was not still contemplating any strong warning for labeling? The final conclusions in Dr. Graham's abstract were actually stronger than Dr. Jenkins had suggested, stating, "this and other studies cast serious doubt on the safety of rofecoxib" at doses greater than 25 milligrams "and its use by physicians and patients."

The GAO may open an investigation of the FDA's treatment of the Vioxx data, and it will be very interesting to see what they're able to uncover. Even without the potential GAO audit, Merck is facing enough problems with a class action lawsuit filed in Canada last week on behalf of 2 Vioxx users who suffered heart attacks. Merck is also accelerating the search for its new CEO for the anticipated retirement of Raymond Gilmartin in 2006.

Comments

[Paul R. M. Schwebel]

I have 5 Vioxx cases.
One involved death by blockage of the left main coronary artery with subsequent perforation of the ventricular septum.
Another in 2001 involved heart attack, pulmonary arrest and death
One case involved stroke, one involved a silent heart attack and two severe ischemic attacks requiring stenting and the last involved heart attack, thrombocytopenia as a complication of treatment, and two stents.
All five cases involved a daily dose of 50mg (high dose)
Two cases were filed in Federal Court with one being dismissed due to the short duration of treatment.
These cases were filed in 2002 by me.
It was particularly disturbing, that Merck saw fit to claim that Vioxx did not cause thrombotic events and that Naprosyn was cardioprotective; making it appear that Vioxx was safe. It was already clear from the Vigor study that Vioxx increased risks for heart problems.
My training as a pharmacist who practiced law alerted me that Merck was trading one subset of problems (GI) for another (heart).
I would appreciate any comments from readers.
Sincerely,

Paul R. M. SChwebel

[Moyra Mclean]

I had been taking Vioxx for over 2years and in the last five months have spent three weeks in hospital and been very ill with something that no one could diagnose, until I went to a specialist and he informed me that it looks like something has happened with my bowel that he has never seen before,he took the cat scan to other specialists and he said they too had never seen anything like it seemed like my whole bowel has herniased...I had been saying to my Dr on many occasions how safe is vioxx? I am positive it has done this to me Would you have an opinion on this....On top of that three weeks ago my left hand started to shake for no reason, My GP treated it as stroke, and has given me tablets to carry with me now whenever it happens...