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Eli Lilly halted a Phase III trial of its evacetrapib after an interim analysis found that the lipid-modulating drug had a low probability of being effective. Lilly is now the third big pharma company to scrap a Phase III cholesteryl ester transfer protein (CETP) inhibitor for the treatment of atherosclerosis, reducing the odds for the few remaining companies, including Merck & Co., that are still invested in the space.

The first high-profile failure of a CETP inhibitor came in 2006, when Pfizer was forced to discontinue development of torcetrapib after the drug increased the risk of death and heart problems. Drug developers including Roche, Lilly and Merck eventually concluded that torcetrapib's failure was not likely to be a class effect, and cautiously advanced their programmes. In 2012, however, Roche pulled the plug on its dalcetrapib in Phase III after an interim analysis suggested that the trial was unlikely to meet its end points.

The results bode poorly for Merck's anacetrapib, which is in Phase III development. An interim efficacy analysis of a key pivotal trial is expected by the end of this year, and the trial is due to complete in 2017. Amgen, too, could be affected. In September, Amgen said it will gain rights to the Phase III CETP inhibitor DEZ-001 through the US$300-million acquisition of the biotech company Dezima Pharma.

One remaining glimmer of hope for the class is the possibility that a set of genetic polymorphisms can predict which patients will benefit from CETP inhibition (Circ. Cardiovasc. Genet. 8, 372–382; 2015). Earlier this year the biotech DalCor acquired rights to dalcetrapib on the basis of these findings, and the company plans to launch a Phase III trial of that drug this year that will only enrol patients with appropriate genetic profiles.