Dalcetrapib (INN, codenamed JTT-705) is a

CETP inhibitor A CETP inhibitor is a member of a class of drugs that inhibit cholesterylester transfer protein (CETP). They are intended to reduce the risk of atherosclerosis (a cardiovascular disease) by improving blood lipid levels. At least three medications ...

which was being developed by

Hoffmann–La Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

until May 2012. The drug was aimed at raising the blood levels of

HDL cholesterol High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...

. Prevailing observations indicate that high HDL levels correlate with better overall cardiovascular health, though it remains unclear whether raising HDL levels consequently leads to an increase in cardiovascular health. A 24-week

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

showed that dalcetrapib did increase HDL-C levels, supporting the agent's desired effect. Further, the dal-PLAQUE phase IIb trial found evidence of

plaque Plaque may refer to: Commemorations or awards * Commemorative plaque, a plate or tablet fixed to a wall to mark an event, person, etc. * Memorial Plaque (medallion), issued to next-of-kin of dead British military personnel after World War I * Pla ...

reduction. Plaque reduction is an anticipated observation following an increase in HDL. five phase II trials had started and there was no evidence of the raised blood pressure seen with

torcetrapib Torcetrapib (CP-529,414, Pfizer) was a drug being developed to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease. Its development was halted in 2006 when phase III studies showed excessive all-cause mor ...

. dal-VESSEL phase IIb trial found no evidence of flow-mediated dilatation improvement. A 17% increase of Lp-PLA₂ mass level was noted. Lp-PLA₂ is associated with

coronary heart disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...

and

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

. dal-OUTCOMES phase III trial passed its first interim review in July, 2011, however, development was halted on May 7, 2012 “due to a lack of clinically meaningful efficacy.”. The results of dal-OUTCOMES III were published in November, 2012. A pharmacogenomic

genome-wide association study In genomics, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an observational study of a genome-wide set of Single-nucleotide polymorphism, genetic variants in different i ...

(GWAS) reported that patients from the dal-OUTCOMES study bearing a protective allele at SNP rs1967309 in the ADCY9 gene may have benefited from dalcetrapib therapy. Changes in inflammation and cholesterol efflux capacity may in part explain the benefits associated with the protective genotype. The Dal-GenE trial is currently validating these observations. This clinical trial is a randomized placebo-controlled study to evaluate the effects of dalcetrapib on cardiovascular risk in patients with recent acute coronary syndrome bearing the protective genotype.

References

{{Lipid modifying agents Anilides Hoffmann-La Roche brands Thioesters Abandoned drugs

See also

References