Pharmaceutical company Pfizer Inc. stopped development of torcetrapib, a drug intended to replace Lipitor, after a clinical test involving 15,000 people taking the experimental medicine resulted in a higher rate of deaths than expected.

Torcetrapib was the first in a new class of compounds known at CETP inhibitors that target the cholesterol ester transfer protein (CETP), which regulates how good cholesterol (HDL) helps flush away bad cholesterol. It was hoped the drug would reduce the buildup of plaque in blood vessels that can cause heart attacks.

The clinical test found that 82 patients taking torcetrapib and Lipitor died, compared with 51 who died while taking Lipitor alone. Patients taking torcetrapib also showed an increase in chest pain and congestive heart failure.

Even before the clinical test, there was concern that while torcetrapib might increase good cholesterol, it could also raise blood pressure and increase the risk of heart attack and stroke. Other CETP inhibitors in development that do not show a blood-pressure problem may succeed.

Dr. Steven E. Nissen of the Cleveland Clinic said the type of good cholesterol affected by CETP inhibitors may not be the type that gets rid of bad cholesterol effectively. Also, some forms of good cholesterol may make matters worse.

Nissen is leading an additional study of torcetrapib that uses imaging techniques to see whether the drug reduces plaque in the arteries. If plaque is not reduced or if the study finds that heart disease progresses despite rising levels of good cholesterol, that may suggest that the whole class of CETP inhibitors will not work.

Sources: Scott Hensley, "Demise of a blockbuster drug complicates Pfizer's revamp," Wall Street Journal, December 4, 2006.