Dalcetrapib
Update captures dal-OUTCOMES futility and the decision by Roche to end the dalcetrapib program in May 2012 (Future Cardiol 2012)
Original title: An update on the clinical development of dalcetrapib (RO4607381), a cholesteryl ester transfer protein modulator that increases HDL cholesterol levels
This update reviews the clinical development of dalcetrapib, a CETP modulator, alongside the more potent CETP inhibitor anacetrapib, both then in phase III trials aiming to reduce cardiovascular events by raising HDL cholesterol. At the 600 mg dose selected for dal-OUTCOMES, dalcetrapib was expected to inhibit CETP activity and raise HDL-C by approximately 30% each, with limited LDL-C effect, and unlike torcetrapib it did not raise blood pressure or aldosterone; in the dal-PLAQUE imaging study, dalcetrapib reduced enlargement of total vessel area over time. In May 2012, following the second interim analysis of dal-OUTCOMES, the Data and Safety Monitoring Board recommended stopping the trial for lack of clinically significant benefit, and Roche terminated both the study and the wider dalcetrapib (dal-HEART) program. The authors note dalcetrapib had tested whether an isolated, moderate HDL cholesterol elevation alone prevents cardiovascular events, in contrast to the more potent dual lipid effects of anacetrapib.
Original abstract
CETP is the target of CETP inhibitors such as anacetrapib and the modulator dalcetrapib. Both molecules have entered Phase III clinical trials, with the ultimate goal of reducing cardiovascular events by raising HDL cholesterol. At the 600-mg dose selected for the dal-OUTCOMES study, dalcetrapib is expected to inhibit CETP activity by approximately 30% and raise HDL-C by approximately 30% with limited effects on LDL cholesterol. Importantly, dalcetrapib does not raise blood pressure or aldosterone levels, two effects previously associated with the CETP inhibitor torcetrapib. Dalcetrapib has been well tolerated at the 600-mg dose. In the dal-PLAQUE atherosclerosis imaging study, dalcetrapib reduced the enlargement of total vessel area over time. In May 2012, following the results of the second interim analysis of dal-OUTCOMES, the Data and Safety Monitoring Board recommended stopping the study owing to a lack of clinically significant benefit, which was followed by Roche's (Basel, Switzerland) decision to terminate the study and the dalcetrapib program (dal-HEART). Contrary to anacetrapib, a potent CETP inhibitor that markedly increases HDL cholesterol and significantly reduces LDL cholesterol, dalcetrapib has allowed us to test the hypothesis that an isolated, moderate elevation in HDL cholesterol prevents cardiovascular events.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.