Anacetrapib
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IUPAC name
(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({2-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]-5-(trifluoromethyl)phenyl}methyl)-4-methyl-1,3-oxazolidin-2-one
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3D model (Jmol)
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| C30H25F10NO3 | |
| Molar mass | 637.51 g·mol−1 |
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Anacetrapib (USAN,pINN; codenamed MK-0859, Merck) is a CETP inhibitor being developed to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease.
At the 16th International Symposium on Drugs Affecting Lipid Metabolism (New York, Oct 4-7, 2007), Merck reported on a Phase IIb study. The eight week study reported dosage correlated reduction in LDL-C and increases in HDL-C levels with no corresponding increases in blood pressure in any cohort. The increase in HDL was particularly significant, averaging 44 percent, 86 percent, 139 percent and 133 percent at doses of 10 mg, 40 mg, 150 mg and 300 mg.
Merck performed a dose-ranging study of anacetrapib, with the results presented in 2009.
A 2013 study of 407 Japanese patients found anacetrapib reduced LDL and raised HDL alone or with atorvastatin.
A concern raised in October 2013 is related to the time that the drug remains in people's bodies after they stop taking it. The report shows that even after 4 years the levels of the medicine were still detectable.
A 2014 study found HDL and drug levels remained elevated 2 to 4 years after discontinuation.
Merck started a Phase III trial to assess the drug's effects on LDL, HDL, clinically measurable cardiovascular events, and safety; It was code-named DEFINE (Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib), and was described as a medium-sized safety and efficacy trial.
Early results from the DEFINE trial were presented on November 17 at AHA2010, a meeting of the American Heart Association. At 100 mg dosage, LDL decreased by 36%, lipoprotein(a) decreased by 36.4%, while HDL increased by 138%. Systolic blood pressure showed no increase, and there was no association with increased CVD death or events. In 2012 the results were updated to 39.8% of LDL decrease.
Cardiologist Steve Nissen (in 2010) described DEFINE as a medium-sized safety trial intended to find out "whether anacetrapib would show the same increase in adverse cardiovascular events that was seen with torcetrapib." Fortunately, anacetrapib did not. In his opinion the DEFINE study was too small to show a clear benefit, but the trends in the major adverse cardiovascular events were going in the right direction.
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