Merck & Co., Inc., anacetrapib (formerly known as MK-0859), its investigational selective cholesteryl ester transfer protein (CETP) inhibitor, significantly reduced LDL-cholesterol (LDL-C) and Apolipoprotein B (Apo B) and increased HDL-cholesterol (HDL-C) and Apolipoprotein A-1 (Apo A-1) both as monotherapy and in combination with atorvastatin 20 mg compared to placebo in patients with dyslipidemia.
The primary endpoint of the eight-week study was LDL-C reduction, with secondary endpoints of HDL-C increases and effects on other lipoproteins and apolipoproteins and blood pressure evaluated across ten treatment groups. In the study, anacetrapib monotherapy at doses of 10 mg, 40 mg, 150 mg and 300 mg reduced LDL-C levels by 16 per cent, 27 per cent, 40 per cent, and 39 per cent, and increased HDL-C levels by 44 per cent, 86 per cent, 139 per cent, and 133 per cent compared to placebo (two and four percent, respectively) in a dose dependent manner. Anacetrapib co-administered with atorvastatin, across all doses studied, also produced significant incremental reductions in LDL-C and increases in HDL-C compared to atorvastatin alone.
"The favourable lipid effects seen in this study with multiple doses of anacetrapib were significant, and confirm the continued evaluation of the clinical benefits of CETP inhibitors in the treatment of dyslipidemia," said Daniel Bloomfield, MD, clinical research, Merck Research Laboratories.
"The decreased LDL-C concentrations, increased HDL-C concentrations and no demonstrable increase in blood pressure seen with anacetrapib are particularly encouraging results of this study." In addition to these phase IIb study results, Merck continues to carefully evaluate all of its data and other available information as its plans for anacetrapib are evaluated.
CETP inhibitors work by inhibiting cholesteryl ester transfer protein (CETP), a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins, resulting in higher HDL-cholesterol levels (the "good" cholesterol-containing particle) and reducing LDL-cholesterol levels. It is hypothesized that increased CETP activity may increase the risk for atherosclerosis (the formation of plaques in arteries) and coronary heart disease (CHD) due to increased LDL-C formation, especially in people with elevated triglycerides.
Dyslipidemia is the elevation of LDL-C and/or triglycerides or a low HDL-C level that contributes to the development of atherosclerosis. Major modifiable risk factors for atherosclerotic disease include hypertension, diabetes, obesity, smoking and high levels of total cholesterol or LDL-C. Low levels of HDL-C also increase a person's chances of developing atherosclerosis.