Evacetrapib
Names | |
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IUPAC name
Trans-4-({(5S)-5-[{[3,5-bis(trifluoromethyl)phenyl]methyl}(2-methyl-2H-tetrazol-5- yl)amino]-7,9-dimethyl-2,3,4,5-tetrahydro-1H-benzazepin-1-yl}methyl) cyclohexanecarboxylic acid
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Other names
LY2484595
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Identifiers | |
3D model (
JSmol ) |
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ChEMBL | |
ChemSpider | |
ECHA InfoCard
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100.227.032 |
KEGG | |
PubChem CID
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UNII | |
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Properties | |
C31H36F6N6O2 | |
Molar mass | 638.659 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Evacetrapib was a
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[4]) 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.[2] Anacetrapib is the fourth CETP inhibitor being tried for cardiovascular benefit [1]
Trials
ACCELERATE
In a 2014 study in 165 Japanese patients Evacetrapib decreased CETP activity alone or in combination with atorvastatin.[5]
Phase III trial was terminated due to futility.[6][7] 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.[8] ACCENTUATE is studying patients with hyperlipidemia or diabetes.[9]
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.[10] 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.[10] The ACCELERATE trial led by Dr. Stephen J. Nicholls who observed,[10]
"“It’s the most mind-boggling question. How can a drug that lowers something that is associated with benefit not show any benefit?"
— Dr. Stephen J. Nicholls 2016
References
- ^ PMID 21957197.
- ^ S2CID 6965741.
- PMID 22089718.
- PMID 23126252.
- PMID 24786356.
- ^ "Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes - ACCELERATE".
- ^ "A Study of Evacetrapib in High-Risk Vascular Disease (ACCELERATE)".
- ^ "Lilly to Discontinue Development of Evacetrapib for High-Risk Atherosclerotic Cardiovascular Disease". Archived from the original on 2015-11-03.
- ^ "Study of Evacetrapib (LY2484595) in Participants With High Cholesterol (ACCENTUATE)". 25 September 2019.
- ^ a b c Kolata, Gina (3 April 2016). "Dashing Hopes, Study Shows a Cholesterol Drug Had No Effect on Heart Health". New York Times. Retrieved 4 April 2016.