Merck & Co. (NYSE: MRK) reported that its investigational oral PCSK9 inhibitor enlicitide decanoate demonstrated significantly greater reductions in LDL cholesterol compared to other oral non-statin therapies in a phase 3 clinical trial.

The CORALreef AddOn study compared enlicitide to bempedoic acid, ezetimibe, or their combination when added to background statin therapy in adults with hypercholesterolemia. At eight weeks, enlicitide reduced LDL cholesterol by 64.6% from baseline when added to statin treatment.

Enlicitide showed superior performance versus comparators, reducing LDL cholesterol by 56.7% compared to bempedoic acid, 36.0% compared to ezetimibe, and 28.1% compared to bempedoic acid with ezetimibe. All comparisons were statistically significant with p-values less than 0.001.

The drug also achieved better results for secondary endpoints. Enlicitide reduced apolipoprotein B by 54.6% from baseline and non-HDL cholesterol by 58.0% from baseline, both significantly greater than the comparator treatments.

In December 2025, the FDA selected enlicitide to receive the Commissioner's National Priority Voucher. The safety profile was consistent with previous phase 3 trials, with no serious adverse events, discontinuations due to drug-related adverse events, or discontinuations due to drug-related serious adverse events reported for patients treated with enlicitide.

The results were presented at the American College of Cardiology's Annual Scientific Session and published simultaneously in JACC. This represents the third positive phase 3 study for enlicitide, which is designed to be the first approved oral PCSK9 inhibitor.

Information in this article is based on a company press release.