Cholesteryl ester transfer protein (CETP) is among the most prominent new targets for the treatment of dyslipidemia, despite a high level of failure in the past.
With eight products in development across the industry, CETP is a protein responsible for transferring lipids such as cholesterol from high-density lipoproteins (HDL) (good cholesterol) to very low and low-density lipoproteins (LDL) (bad cholesterol). It can also reverse this, changing low-density to high-density.
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In people with fatty plaque and high cholesterol, it is common to see raised CETP levels, an increased level of lipid transfer between good and bad cholesterol transports, or both. This suggests that CETP may play a role in cardiovascular disease (CVD) development.
It now looks likely that a CETP therapy will make it to market that is capable of lowering bad cholesterol while raising good cholesterol and reversing plaque build-up in arteries.
Leading the race
Anacetrapib is in late-stage development by Merck and Co for the treatment of CVD conditions, including forms of high cholesterol and coronary artery disease. It is expected to be approved in 2018.
The DEFINE trial demonstrated an LDL reduction of 39.8% and a HDL increase of 138.1%, with good tolerability and acceptable side effects.
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By GlobalDataThere was also an LDL cholesterol decrease of 18.6% and a HDL increase of 73%, 12 weeks after drug cessation.
This suggests strong potential for drugs that act in multiple ways to treat high cholesterol and atherosclerosis. This is especially so for Anacetrapib, which could be the first CETP therapy to reach the market.
Not over the finish line yet
The future of a developmental drug is never certain, and Anacetrapib has failed in clinical trials in the past for the treatment of cholesterol abnormalities.
The role of CETP in CVD risk is also complex. It has been found that the effects of CETP are moderated by lifestyle factors including exercise and smoking.
In addition, the effects of CETP gene deficiency on CVD risk was found to be modified by baseline HDL cholesterol levels. It increases risk in patients with low-to-moderately increased HDL cholesterol levels, but decreases risk in those with high HDL levels.
Despite these barriers, it seems likely that Anacetrapib will impact the market considerably in the near future.
If approved, sales of the drug are expected to reach $822m by 2023, as numerous patients look to take advantage of its powerful cholesterol-influencing properties.
http://www.ajconline.org/article/S0002-9149%2813%2901939-5/fulltext
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