The Demise of a New Cholesterol Drug

Dr. Kang Health Pro
  • “Torcetrapib: the $800 million dollar failure”

    “Pfizer stock drops 10.6%!”

    “This spells the death of what is arguably the most important development at Pfizer!”

    These are just some of the headline grabbers I saw in December when Pfizer, the world’s largest drug maker, announced that it was abandoning its research and development on its novel cholesterol medication called torcetrapib.

    Although the press seemed to mainly focus on the financial loss, more importantly is the loss that patients and physicians felt when this novel cholesterol medicine actually proved to be harmful to people.
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    Torcetrapib belongs to a novel class of cholesterol medication called cholesterol-ester-transfer-protein (CETP) inhibitors. In essence, these drugs mainly increase good HDL cholesterol and to a lesser extent lower bad LDL cholesterol. To date, fibric acid derivatives and niacin are the only drugs that can raise HDL appreciably on the order of 20-30%. CETP inhibitors are much more potent in raising HDL (40-50% increase in HDL) and lower LDL ~
    What happened? Torcetrapib was being studied in a large research trial involving 15,000 people. People were either given torcetrapib with atorvastatin (aka, Lipitor – a statin medicine) or just atorvastatin alone. The researchers hoped that the combination drug would lower the risk of heart attacks, strokes, and deaths.

    Early on it became apparent that torcetrapib was associated with an increase in blood pressure. The study was then stopped prematurely when it was discovered that more people died when taking the combination medicine. There were two explanations for this increased risk with torcetrapib. Firstly, torcetrapib raised blood pressure by 3-4 points thereby worsening high blood pressure.

    This may have directly translated into an increase in heart attacks and strokes. Secondly, the type of HDL that torcetrapib raises may not be the right type or may be dysfunctional and therefore would not offer any protection. Scientists are currently trying to figure out whether this problem applies to only to torcetrapib or all CETP inhibitors.

    Is this the end of the CETP inhibitors? Not necessarily. Merck and Roche are currently investigating their own CETP inhibitors. It waits to be seen if these drugs will be different than torcetrapib. So, if you want raise your HDL to be > 40mg/dl in today’s world, here’s what you can do:

    1. Stop smoking
    2. Exercise regularly
    3. Lose weight if you are overweight or obese
    4. Substitute unsaturated fats for saturated fats in your diet
    5. Eat soluble fiber such as those found in fruits and vegetables
    6. Consider drinking 1-2 alcoholic beverages/day but no more than that
    7. Take prescription medicine if needed such as gemfibrozil, fenofibrate, niacin, or a statin

    As to whether you should sell your Pfizer stock, it did recover somewhat. But I’ll leave that up to you to decide.

Published On: January 18, 2007