Is there life for CETP inhibitors after the death of torcetrapib?

Dr. Kang Health Pro
  • In the beginning of this year, I wrote two articles concerning torcetrapib, the $800 million failure of Pfizer to develop a new type of cholesterol medication. This novel medication called a CETP (cholesterol ester transfer protein) inhibitor is able to markedly raise HDL, but unfortunately was found to increase the risk of death. The increased risk of death was believed mainly due to an unexpected increase in blood pressure but there was some concern that the type of HDL produced may not be beneficial. New information from a large study called ILLUMINATE presented at the 2007 American Heart Association meeting in Orlando, FL, shed some more light on CETP inhibitors but was unable to resuscitate torcetrapib.

    Add This Infographic to Your Website or Blog With This Code:


    Little doubt remains that in general torcetrapib is a bad drug. However, information is now available that shows that the type of HDL produced by torcetrapib was beneficial. So why was torcetrapib harmful? It turns out that this drug apparently raises the level of a hormone called aldosterone. Aldosterone is very important in the handling of sodium and potassium. High levels of this hormone can increase blood pressure which can then lead to more heart attacks, stroke, and death.


    Now that we have a better understanding as to why torcetrapib was a harmful drug, so what? Why keep beating a dead horse so to speak. It turns out that there are 2 new CETP inhibitors currently being developed by the drug companies Merck and Roche. The increase in aldosterone levels seen with torcetrapib may not be a CETP inhibitor class effect but rather specific to only torcetrapib. In animal studies, anacetrapib, another CETP inhibitor under development by Merck, does not seem to increase aldosterone levels. One other concern with torcetrapib was that more deaths were observed related to infection and cancer. But, it's not clear if the drug caused these problems or rather accelerated death in people who already had an infection or cancer. Regardless, this is another potential risk that needs to carefully be monitored during the development of any new CETP inhibitors.


    On a more positive note, the HDL produced by torcetrapib seemed to be functional, meaning that it contributed to heart protection. This conclusion came from the fact that those people who had the greatest increase in HDL on torcetrapib had the lowest risk of heart attack or death. The effect of torcetrapib on cholesterol was quite impressive: 72% increase in HDL and a 25% reduction in LDL.


    In summary, torcetrapib remains dead and buried, but its demise does not necessarily mean the end of CETP inhibitors. By using the insights gained from the failure of this drug, hopefully future generations of CETP inhibitors can avoid toxicity and ultimately be a benefit to us. But the development of any new CETP inhibitor will be a slow and cautious one. It may be several more years before CETP inhibitors will get another chance to prove themselves to be either remedy or poison.


    Add This Infographic to Your Website or Blog With This Code:

    Related Information:


    Was Torcetrapib's Crash and Burn Fatal for this Class of Drug?

Published On: December 13, 2007