Torcetrapib

Pfizer (CP-529,414)

Status Terminated December 2006 for excess mortality

The first CETP inhibitor to reach phase 3 and the reason the class carries a shadow. ILLUMINATE randomised 15,067 patients and was halted in December 2006 when the torcetrapib arm showed excess mortality. The cause was traced to an off-target effect on aldosterone and blood pressure rather than to CETP inhibition itself, which is why the class survived at all.

Mechanism. A potent CETP inhibitor that raised HDL-C by around 70% and lowered LDL-C. It also raised blood pressure, increased aldosterone and shifted serum electrolytes, effects that turned out to be off-target and molecule-specific.

The trial. ILLUMINATE (NCT00134264) enrolled 15,067 patients on atorvastatin. The data monitoring board stopped it in December 2006 for an excess of deaths and cardiovascular events in the torcetrapib arm. A safety follow-up study (NCT00452842) tracked 26,784 participants afterwards.

Why the class continued. Had the harm been intrinsic to CETP inhibition, the field would have ended in 2006. The evidence that it was not, chiefly the absence of a pressor effect with dalcetrapib, anacetrapib, evacetrapib and obicetrapib, is what allowed three more drugs to be developed. Blood pressure has been a mandatory endpoint in every CETP programme since, which is why safety sections in this library carry so much detail on it.

The lesson everyone quotes. Torcetrapib is the standard teaching example of a surrogate endpoint moving in the desired direction while patients do worse.

Page updated 18 August 2026.