Merck & Co's anacetrapib hit its primary end point in a large phase III cardiovascular outcomes trial, defying industry expectations for a drug class that many experts had dismissed. But questions remain about whether the cholesteryl ester transfer protein (CETP) inhibitor will meet the regulatory or commercial cut.

CETP inhibitors are lipid-modulating drugs that increase high-density lipoprotein (good) cholesterol and reduce low-density lipoprotein (bad) cholesterol. Despite high hopes for these drugs as a means of reducing cardiovascular risk, several candidates have bombed out in clinical trials. Pfizer pulled the plug on its phase III candidate torcetrapib in 2006 after the drug increased the risk of death. Roche stopped phase III development of its dalcetrapib owing to futility in 2012, and Eli Lilly halted phase III development of evacetrapib in 2015 for the same reason.

Merck is one of just a few companies that has persevered. In August, the company reported detailed results from a 30,500-patient phase III trial that showed that the rate of major coronary events with anacetrapib was 10.8% versus 11.8% with placebo, a relative risk reduction of 9%. The data were presented at the European Society of Cardiology Congress in Barcelona in August and published in the New England Journal of Medicine .

Cardiologists called this treatment effect modest, and were disappointed that the treatment did not appear to confer a mortality benefit. In light of the past failures of CETP inhibitors, some specialists said further clinical trials would be needed to validate the new findings. Merck is evaluating the data and deciding on its next steps.

At least two other companies are also still holding out hope for CETP inhibitors. DalCor Pharmaceuticals licensed Roche's dalcetrapib in 2015, and is running a phase III trial of the drug in a genetically defined population of patients with ADCY9 polymorphisms. Amgen still lists its CETP inhibitor AMG899 in its phase II pipeline.