Torcetrapib for increasing HDL cholesterol

On April 7, 2004 Pfizer announced preliminary results of a Phase I trial with torcetrapib, its experimental therapy for increasing HDL cholesterol. A study was published in the April 8, 2004 issue of the New England Journal of Medicine, involving 19 patients. The results showed that torcetrapib significantly increased the level of high-density lipoprotein (HDL) in the study participants when given twice daily over a period of 8 weeks. Participants were treated with the experimental drug alone or in combination with the cholesterol lowering drug Lipitor. The subgroup treated with 120 milligram of torcetrapib daily experienced a 46% increase in HDL, while patients treated with both torcetrapib and Lipitor experienced a 61% increase in HDL levels.

Torecetrapib is a cholesterol ester transfer protein (CETP) inhibitor. CETPs play a role in the conversion of HDL cholesterol into LDL cholesterol. It is thought that interfering with the activity of CETP increases HDL levels. There are a number of chemical CETP inhibitors in the pre-clinical stage of development. At least one other CETP inhibitor, JTT-705, has been tested in human clinical trials.

There are many large-scale clinical trials that demonstrate that the lowering of low-density lipoproteins (LDL cholesterol) with statins has significant effects on a variety of clinical outcomes. While it is generally accepted in the medical literature that low levels of HDL cholesterol increase the risk of coronary artery disease, the data supporting the beneficial effects of elevating HDL cholesterol is epidemiologic in nature. Pfizer will have to demonstrate the safety and efficacy of torcetrapib with respect to some hard cardiovascular endpoints, similar to what has been done with the statins, before this innovative therapy can have a substantial impact on the estimated 100 million Americans with abnormal cholesterol levels.

It appears as though Pfizer continues to devote considerable resources to the development of torcetrapib. Pfizer reportedly paid $1.3 billion to acquire the company that developed torcetrapib and has earmarked $800 million for ongoing clinical trials. Combining Lipitor and torcetrapib in a single treatment for dyslipidemia could significantly increase per patient cost. Biohorizon currently designates torcetrapib a Moderate Impact Technology and recommends no assessment activities at this time.

Technology Details
Target Disease / Indication
Low HDL/Coronary Artery Disease

Technology Classification
Drug

Body System
Cardiovascular System

Program Area
Medicine/Cardiology

Regulatory Status
Phase I

BioHorizon Impact Score
64/100 – Moderate