Pfizer Pulls the Plug on Potential Plaque Buster

By Russell H. Samson, MD

Pfizer Inc. decided to halt all further clinical investigation of its drug torcetrapib, an experimental drug that raises HDL cholesterol by inhibiting cholesterol ester transfer protein (CETP). Of patients taking torcetrapib with Pfizer's Lipitor, 82 died in a study of 15,000 enrollees, a 60% higher rate than among those who got only Lipitor. That result caused Pfizer to halt work on torcetrapib just days after the New York-based company said it would seek U.S. approval to sell the drug in 2007.

Pfizer spent over $1 billion on torcetrapib's development and was about to seek early Food and Drug Administration approval for this new drug. However, recent data showed patients taking this medication had an average increase in blood pressure of 3-4 mm Hg, and it was feared that this would translate into an increase in cardiovascular mortality. Whether this increase in blood pressure caused the increased death rate seen, or whether some other result was the cause, is not yet determined. It also appears that although HDL cholesterol levels were significantly improved, the HDL may have been defective or actually atherogenic, because investigators found that HDL particles in patients taking torcetrapib were larger than those seen in untreated patients. Hoffmann-La Roche Inc. and Merck \& Co. are testing similar drugs that do not appear to have associated blood pressure elevations, but data on these agents are still limited. Accordingly, the entire class of CETP inhibitors will come under more intense scrutiny.

There is still optimism that medications that effect HDL cholesterol may become the next blockbuster lipid agents. However, the negative effects of this study will likely mean that there will not be a commercially available drug for some years.

Currently, the only commercially available medication is Niaspan, the rights to which were recently purchased by Abbott Laboratories (with Kos Pharmaceuticals Inc.) for $3.7 billion. However, facial flushing associated with Niaspan prevents many patients from being able to tolerate the dosages necessary for clinical results.