cetpinhibition.org

Agent

Dalcetrapib

Hoffmann-La Roche, then DalCor Pharmaceuticals (JTT-705, RO4607381)

Status Neutral in dal-OUTCOMES 2012; revived genotype-first, still in trials

A weak CETP modulator that raised HDL-C by about a third and barely touched LDL-C. dal-OUTCOMES randomised 15,871 patients after an acute coronary syndrome and found no benefit. The story then took a turn nobody expected: a pharmacogenomic signal at the ADCY9 locus suggested the drug worked in one genotype, and DalCor has been testing that claim ever since.

Mechanism. Unlike the -trapibs that bind CETP tightly, dalcetrapib modulates it, raising HDL-C without materially lowering apoB. In hindsight that is the whole story: it moved the biomarker the field cared about in 2012 and not the one that mattered.

The trials. dal-OUTCOMES (NCT00658515, n=15,871) was neutral. dal-GenE (NCT02525939, n=6,147) then tested the ADCY9 genotype hypothesis prospectively in patients selected for the responder genotype, completing in 2021. DalCor has a further genotype-defined trial recruiting (NCT05918861, n=2,000, primary completion August 2027).

Why it belongs here. Dalcetrapib is the field's live pharmacogenomic bet, and the reason a reader should not assume the class died in 2017. Whether the ADCY9 signal is real is still an open question, and it is one of the few genuinely testable precision-medicine claims in lipidology.

ClinicalTrials.gov

dalcetrapibgeneticsHDL biologyoutcomes trials

Page updated 18 August 2026.