These drugs have generally failed in clinical trials, either causing a marked increase in deaths (torcetrapib), or having no meaningful clinical improvement despite HDL increases (dalcetrapib, evacetrapib).
Dalcetrapib: development halted in May 2012 when Phase III trials failed to show clinically meaningful efficacy.[6]
Evacetrapib: development discontinued in 2015 due to insufficient efficacy.[7]
Others:
Anacetrapib: In 2017, the REVEAL trial based on more than 30,000 participants showed a modest benefit of the addition of anacetrapib to statin therapy.[8]Merck halted the development of the drug in 2017, concluding it wasn't sufficiently effective to be a competitive product.[9][10]
Obicetrapib (TA-8995, AMG-899): Phase II results were reported in 2015 and Phase III trials beginning in 2023.[11][needs update]
In 2015, a pharmacogenomic sub-study of the dal-OUTCOMES clinical trial on 5,749 individuals identified a genetic variant in the ADCY9 gene which modulates response to dalcetrapib. In patients with the rs1967309 'AA' genotype, there was a significant reduction in the rate of cardiovascular events in the dalcetrapib arm whereas non-carriers were at increased risk.[14] Beginning in 2015, the efficacy of dalcetrapib in the genetic sub-population was being investigated in the dal-GenE trial.[15][needs update]
^Tall AR (March 2007). "CETP inhibitors to increase HDL cholesterol levels". The New England Journal of Medicine. 356 (13): 1364–1366. doi:10.1056/NEJMe078029. PMID17387130.
^Rennings AJ, Stalenhoef A (October 2008). "JTT-705: is there still future for a CETP inhibitor after torcetrapib?". Expert Opinion on Investigational Drugs. 17 (10): 1589–1597. doi:10.1517/13543784.17.10.1589. PMID18808319. S2CID5781222.
^Hovingh GK, Kastelein JJ, van Deventer SJ, Round P, Ford J, Saleheen D, et al. (August 2015). "Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial". Lancet. 386 (9992): 452–460. doi:10.1016/S0140-6736(15)60158-1. hdl:1887/117246. PMID26047975. S2CID7540974.