Evacetrapib was a
drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
under development by
Eli Lilly & Company (investigational name LY2484595) that inhibits
cholesterylester transfer protein
Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It collects triglycerides from very-low-de ...
(
CETP inhibitor). CETP collects
triglycerides from
very low-density lipoproteins (VLDL) or
low-density lipoproteins (LDL) and exchanges them for
cholesteryl ester
300px, Cholesterol oleate, a member of the cholesteryl ester family
Cholesteryl ester, a dietary lipid, is an ester of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl group of cholesterol. Chole ...
s from
high-density lipoproteins (HDL), and vice versa, but primarily increasing high-density lipoprotein and lowering low-density lipoprotein. It is thought that modifying lipoprotein levels modifies the risk of
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
.
The first CETP inhibitor,
torcetrapib, was unsuccessful because it increased levels of the hormone
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
and increased
blood pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
,
which led to excess cardiac events when it was studied.
Evacetrapib does not have the same effect.
When studied in a small
clinical trial in people with elevated LDL and low HDL, significant improvements were noted in their lipid profile.
Evacetrapib evaluation for treatment of high-risk vascular disease was discontinued due to lack of efficacy, as had already happened in the past with two other CETP inhibitors (
torcetrapib and
dalcetrapib) due to increased deaths and little identifiable cardiovascular benefit (despite substantial increases in HDL). Some hypothesize that CETP inhibitors may still be useful in the treatment of dyslipidemia, though significant caution is warranted.
is the fourth CETP inhibitor being tried for cardiovascular benefit
Trials
ACCELERATE
In a 2014 study in 165 Japanese patients Evacetrapib decreased CETP activity alone or in combination with atorvastatin.
Phase III trial was terminated due to futility. ACCELERATE studied evacetrapib in participants with high-risk vascular disease (previous myocardial infarction, stroke or peripheral vascular disease, or several cardiovascular risk factors). An interim analysis performed in October 7 led the Data Monitoring Committee to support a recommendation to stop the study as the totality of evidence suggested that evacetrapib was unlikely to be superior to placebo. ACCENTUATE is studying patients with hyperlipidemia or diabetes.
On April 3, 2016 at the
American College of Cardiology cardiologists first saw the data for Eli Lilly's ACCELERATE trial of Evacetrapib involving 12,000 patients.
They were "stunned" by the result which showed there was no benefit from taking evacetrapib—434 participants who took Evacetrapib died from "cardiovascular disease, such as a heart attack or a stroke" and 444 participants who took a placebo died.
The ACCELERATE trial led by Dr. Stephen J. Nicholls who observed,
References
{{Lipid modifying agents
Hypolipidemic agents
Tetrazoles
Trifluoromethyl compounds
Carboxylic acids
Abandoned drugs