Another Nail in the Coffin for Torcetrapib

Dr. Kang Health Pro
  • Back in January of this year, I wrote an article called The Demise of a New Cholesterol Drug, concerning the development of a new class of cholesterol drugs called CETP (cholesterol ester transfer protein) inhibitors. These drugs have the unique property of markedly raising good HDL cholesterol and were thought to be able to prevent the development of heart disease.

    Unfortunately, torcetrapib, one of the first drugs to make it to wide scale human testing and produced by Pfizer, turned out to be a loser. It did raise good HDL and lowered bad LDL but it was also associated with an increased risk of heart attack, stroke, and death. Development of the drug was therefore stopped.

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    Now, further information just released at the AmericanCollege of Cardiology Scientific Meetings in New Orleans this past Monday show that torcetrapib also was not effective in preventing the development of atherosclerosis in carotid arteries. In fact, no effect was seen at all despite huge increases in HDL. So, not only did torcetrapib not work in preventing atherosclerosis, it was also harmful to people. Again, the reasons for this failure are not clear.

    There are two postulated reasons:

    1) the increase in blood pressure led to an increase risk of bad outcome that offset any potential benefit of the increase in HDL

    2) the type of HDL produced by the drug is not protective

    After all, people who have a natural CETP inhibition on account of genetics have very low rates of heart disease. One important question remains: is this negative effect of torcetrapib representative of all drugs in this class? Roche and Merck are currently developing their own CETP inhibitors. 


    I think Dr. Phillip Barter, one of the lead scientists for these studies, summed it up best when he was quoted as saying,

    “There are some things that you can say absolutely. One is that torcetrapib does not work…My take on the data is that they confirm torcetrapib is not a good drug, but they don’t tell us anything about the mechanism of the excess mortality.”

    Patients, doctors, and Wall Street eagerly await Roche and Merck’s decisions about whether they will continue to fund research on their own version of CETP inhibitors.  We’ll just have to keep our eye on the Wall Street Journal in the upcoming months.

Published On: March 27, 2007