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).
Torcetrapib, failed in 2006 due to excess deaths in Phase III clinical trials.
Dalcetrapib, development halted in May 2012 when Phase III trials failed to show clinically meaningful efficacy.
Evacetrapib, development discontinued in 2015 due to insufficient efficacy.
Obicetrapib (TA-8995, AMG-899), Phase II results reported in 2015, discontinued in 2017
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. Despite the successful trial, Merck halted the development of the drug.
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. The efficacy of dalcetrapib in the genetic sub-population is currently being investigated in the dal-GenE trial.
^Hovingh, G Kees; Kastelein, John J P; Van Deventer, Sander J H; Round, Patrick; Ford, John; Saleheen, Danish; Rader, Daniel J; Brewer, H Bryan; Barter, Philip J (2015). "Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): A randomised, double-blind, placebo-controlled phase 2 trial". The Lancet. 386 (9992): 452–60. doi:10.1016/S0140-6736(15)60158-1. PMID26047975.
^Bowman L, Hopewell JC, Chen F, Wallendszus K, Stevens W, Collins R, Wiviott SD, Cannon CP, Braunwald E, Sammons E, Landray MJ (September 2017). "Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease". The New England Journal of Medicine. 377 (13): 1217–1227. doi:10.1056/NEJMoa1706444. PMID28847206.