Drug companies are attempting to come up with a drug that raises HDL cholesterol levels. Will torcetrapid be the first? If torcetrapid is approved for this purpose, will it have more benefits than side effects? Much remains to be still learned about this medication. Let's keep in mind that sometimes a side effect of a medicine can be worse than the disease. Statins are known to cause myopathy. Will torcetrapid have a serious side effect that will be found out after approval?
2006 - Pfizer cut off torcetrapib's trial because of "an imbalance of mortality and cardiovascular events" associated with its use.
2006 - Pfizer says that it will apply for approval to sell a promising new heart treatment as a standalone pill — rather than only in combination with Lipitor, Pfizer’s best-selling cholesterol treatment. The new drug, torcetrapib, is still being tested in clinical trials and is at least 18 months from federal approval. But some cardiologists say it has the potential to become a new treatment for heart disease. Clinical trials show that torcetrapib raises the levels of so-called good cholesterol, a novel approach to preventing heart attacks and strokes. Previously, Pfizer had said it would sell torcetrapib only in combination with Lipitor, one of several medicines called statins that lower levels of LDL, or bad cholesterol. Cholesterol-reducing medicines are the largest prescription drug category, with worldwide sales of $32 billion last year. By offering torcetrapib only in a combination pill, Pfizer would have forced patients taking other statins — like Zocor, from Merck — to switch to Lipitor if they wanted torcetrapib’s benefits. In an interview last year, Dr. John L. LaMattina, Pfizer’s top scientist, defended the company’s plans, saying that the costs of testing torcetrapib alongside every statin would be prohibitive. Already, Pfizer says it is spending $800 million to develop torcetrapib. Pfizer is the world’s largest drug maker, with sales of $51 billion and a profit of $8 billion last year.
Effects of an Inhibitor of Cholesteryl Ester Transfer Protein on HDL Cholesterol
NEJM, 2004. Margaret E. Brousseau, Ph.D., Ernst J. Schaefer, M.D.. Wolfe, B.S., LeAnne T. Bloedon, M.S., R.D., Andres G. Digenio, M.D., Ph.D., Ronald W. Clark, M.S., James P. Mancuso, Ph.D., and Daniel J. Rader, M.D. From the Lipid Research Laboratory, Division of Endocrinology, Metabolism, Diabetes, and Molecular Medicine, New England Medical Center and Tufts University School of Medicine, Boston; the Department of Medicine and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia; and the Departments of Cardiovascular and Metabolic Diseases and Clinical Biostatistics (J.P.M.), Pfizer, Groton, Conn.
Decreased high-density lipoprotein (HDL) cholesterol levels constitute a major risk factor for coronary heart disease; however, there are no therapies that substantially raise HDL cholesterol levels. Inhibition of cholesteryl ester transfer protein (CETP) has been proposed as a strategy to raise HDL cholesterol levels. We conducted a single-blind, placebo-controlled study to examine the effects of torcetrapib, a potent inhibitor of CETP, on plasma lipoprotein levels in 19 subjects with low levels of HDL cholesterol, 9 of whom were also treated with 20 mg of atorvastatin daily. All the subjects received placebo for four weeks and then received 120 mg of torcetrapib daily for the following four weeks. Six of the subjects who did not receive atorvastatin also participated in a third phase, in which they received 120 mg of torcetrapib twice daily for four weeks. Results: Treatment with 120 mg of torcetrapib daily increased plasma concentrations of HDL cholesterol by 61 percent (P<0.001) and 46 percent in the atorvastatin and non-atorvastatin cohorts, respectively, and treatment with 120 mg twice daily increased HDL cholesterol by 106 percent. Torcetrapib also reduced low-density lipoprotein (LDL) cholesterol levels by 17 percent in the atorvastatin cohort. Finally, torcetrapib significantly altered the distribution of cholesterol among HDL and LDL subclasses, resulting in increases in the mean particle size of HDL and LDL in each cohort. Conclusions: In subjects with low HDL cholesterol levels, CETP inhibition with torcetrapib markedly increased HDL cholesterol levels and also decreased LDL cholesterol levels, both when administered as monotherapy and when administered in combination with a statin.
Curr Pharm Des. 2013. The promise of cholesteryl ester transfer protein (CETP) inhibition in the treatment of cardiovascular disease. There is a strong need to reduce the risk of cardiovascular disease (CVD) beyond the use of statins that lower low-density lipoprotein cholesterol (LDL-C). The inverse relationship of high-density lipoprotein cholesterol (HDL-C) with cardiovascular disease suggests HDL-C raising therapy as a novel target. This review discusses the role of HDL-C in atherogenesis as well as the promise of cholesteryl ester transfer protein (CETP) inhibition in CVD prevention. While genetic studies show conflicting results on correlations between HDL-C and CVD, experimental studies have yielded sufficient encouraging data to proceed with the development of HDL-C raising strategies. CETP inhibition has been shown to successfully increase HDL-C levels in man. However, the first CETP inhibitor tested in phase III trials increased mortality possibly due to torcetrapib-specific vasopressor effects. More recently, dalcetrapib did not show an effect on CVD outcome while raising HDL-C by 30%, thereby refuting the HDL-C hypothesis. Anacetrapib and evacetrapib are currently tested in phase III clinical trials and have not shown adverse effects thus far. Both compounds not only increase HDL-C by 129-151%, they also decrease LDL-C (36-41%) and anacetrapib lowers Lp(a) (17%). Combined, these effects are anticipated to decrease CVD risk and the results will be revealed in 2017.