Torcetrapib was viewed as a new line of therapy in the lowering of cholesterol levels. The drug inhibited the "cholesteryl ester transfer protein" (CETP), which is an important molecule in the liver that transfers cholesterol and regulates cholesterol size.
Torcetrapib is unique in comparison to the other cholesterol-lowering medications: it specifically raised HDL, or “good” cholesterol, levels. This drug has been undergoing clinical trials. Preliminary data published last year in the New England Journal of Medicine indicated that torcetrapib raised HDL cholesterol by almost 60 percent.
On December 2, 2006, however, Pfizer issued a press release, stating that clinical trials and manufacturing of torcetrapib were halted due to safety concerns. The trial, ILLUMINATE, examined atorvastatin (Lipitor®), torcetrapib, and a combination of the two drugs in the treatment of high cholesterol levels and heart disease. Treatment with torcetrapib resulted in the increased incidence of cardiovascular events and death in some of the participants.
There are currently other CETP inhibitors also under development by other drug companies, none of these have shown the same adverse effects to date. How will this affect the future of CETP inhibitors, or other drugs currently under development designed to raise HDL levels? Dr. Rich Fogoros, a well-known cardiologist and also About.com's guide to Heart Disease , had this to say about how the early termination of this study affects the future of CETP inhbitors and other drugs that may raise HDL cholesterol:
"A debate will now ensue as to whether this surprisingly negative result with torcetrapib is related to this particular drug, or whether it is something we can expect to see with all CETP inhibitors. Some will speculate that the increased risk seen with torcetrapib might be related to the small increase in blood pressure recently reported to occur with this drug (in the range of 3-4 mm/Hg). If so, other CETP inhibitors might well prove safe and effective. Others, more pessimistically, will note that the kind of HDL cholesterol that you get with CETP inhibitors is a bit different than the HDL cholesterol that the body normally makes. It is entirely possible that not all HDL cholesterol is "good," and indeed, that some kinds - perhaps even the kind you get with CETP inhibition - may even increase risk. If this latter explanation turns out to be the case, scientists and pharmaceutical houses may have to place on hold the billions of dollars they have invested in HDL-elevators, and go back to the drawing board for more basic science. Today's news, in other words, may throw a damper on more than just Pfizer's stock price."
