DSI Newsletter: Merck & Co., Inc. Voluntarily Withdraws Vioxx

DSI Newsletters, Issue 47:
Merck & Co., Inc. Voluntarily Withdraws Vioxx 30 September 2004

Merck & Co., Inc. (Whitehouse Station, NJ) is voluntarily withdrawing Vioxx (rofecoxib), its arthritis and acute pain medication, from all markets worldwide. The decision of the company, which is effective immediately, is based on new, three-year data from a prospective, randomized, placebo-controlled clinical trial, the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial. The trial, which is being stopped, was designed to evaluate the efficacy of Vioxx 25 mgm in preventing recurrence of colorectal adenomas. In this study, there was an increased relative risk for confirmed cardiovascular events, such as heart attack and stroke, beginning after 18 months of treatment in the patients taking Vioxx compared to those taking placebo. The results for the first 18 months of the APPROVe study did not show any increased risk of confirmed cardiovascular events on Vioxx.
The APPROVe trial was designed to test the effectiveness of Vioxx in the prevention of colon polyps, precursors to cancerous tumors in the colon. It was not designed to test for heart attacks and strokes. It began in 2000 and was scheduled to run through November of 2004.
I am concerned that Merck may have withdrawn the drug prematurely. This is not good news for Merck any way you look at it. Worldwide sales of Vioxx in 2003 were $2.5 Billion and their stock is expected to reduce its earnings per share about $0.55 as a result of its withdrawal. They do have another COX-2 NSAID, Arcoxia on deck, but actions like this can call into question the safety of the whole NSAID class including Advil, Aleve, Motrin, Celebrex, Voltaren, etc....
Of course patient safety is the first concern, but withdrawing Vioxx with the data that I have available to me doesn't make sense. In fact, on the next day, Friday October 1st, I already saw a website www.Vioxx-Legal.com requesting people to sue for being on Vioxx. The scientific way of determining whether Vioxx is bad is to do a study looking specifically at the safety questions in hand. Does long term (greater than 18 months) use of Vioxx increase the risk of heart attack and stroke? The APPROVe trial suggests it might, but is far from proving definitely that it does. The news says the study showed twice the risk with patients on Vioxx. That sounds terrible to the lay public. But, the absolute numbers are not available and it is possible that they reflect very small (insignificant) numbers of people. This is the problem when you do subgroup analysis of a study meant to look at another question.
So the post Vioxx aftermath is to immediately create fear in the hearts and brains of patients that have taken Vioxx. In extreme cases people will be frightened that they looked at a Vioxx pill! The lawyers will say the doctors and Merck should have not used Vioxx in the first place way before any evidence was available to practicing physicians like me. The sales of COX-2 NSAIDs (Celebrex, Bextra, and Arcoxia) will go down a lot and the first generation NSAIDs like Motrin and Aleve will suffer also. Research in NSAIDs will suffer as big Pharma will be frightened away from NSAIDs. The patients will suffer the most in pain.
Patient safety is important and it's easy to see why it appears safer to remove Vioxx while we further study if it's really bad for us and if so, what the true magnitude of the risk really is. There will be a cascade of negative things to follow remove of Vioxx from the market. I think it would have been more prudent to release all the information and allow the doctors to decide which patients to use it in while a new study looks specifically at safety issues. This would be a more favorable balance of safety and efficacy. After all, people will be in more pain now that Vioxx is off the market.
For more information, see the following links:

Sincerely:

Joseph Saponaro, MD, DABIM, FACP, CPI, CCI, CCRI, CCRC, CCRP
Board Certified Internist, JPMC
Principal Investigator, DSI
Diplomat American Board of Internal Medicine
Fellow American College of Physicians
Certified Physician Investigator by the AAPP
Certified Clinical Investigator by the DIA
Certified Clinical Research Investigator by the ACRP
Certified Clinical Research Coordinator by the ACRP
Certified Clinical Research Professional by SoCRA
Member: The American College of Preventive Medicine

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