Merck (NYSE: MRK) reported that enlicitide decanoate, its investigational oral PCSK9 inhibitor, cut LDL-C more than established oral non-statin therapies in adults with hypercholesterolemia receiving background statins in the Phase III setting, a result that matters because it supports the case for a pill-based alternative to injectable PCSK9 drugs. In a category where convenience could shape uptake, the head-to-head win may give Merck a clearer commercial and clinical narrative than placebo-controlled data alone.
In CORALreef AddOn, a Phase III randomized, double-blind, multicenter trial, Merck tested enlicitide against bempedoic acid, ezetimibe, or the combination in adults with hypercholesterolemia and either established ASCVD or risk for a first major ASCVD event while on statin therapy.
The primary endpoint was mean percent change in LDL-C at week eight, and Merck said enlicitide lowered LDL-C by 64.6% from baseline. Against active comparators, the drug reduced LDL-C by 56.7% versus bempedoic acid and 36.0% versus ezetimibe, with the combination arm also trailing enlicitide. As a key secondary readout, enlicitide also drove deeper reductions in apolipoprotein B, which fell 54.6% from baseline, reinforcing that the LDL-C effect was not an isolated marker shift.
The safety profile was positive in the company’s summary, with no clinically meaningful differences in adverse events across groups and no serious adverse events or drug-related discontinuations reported in the enlicitide arm.
What differentiates enlicitide is straightforward: it targets PCSK9 with a once-daily oral macrocyclic peptide, aiming to deliver LDL-C lowering associated with the injectable antibody class in pill form. That sets it apart from oral agents such as ezetimibe, which works through cholesterol absorption rather than PCSK9 blockade. Cross-trial comparisons are limited, but the magnitude of LDL-C lowering Merck reported suggests enlicitide could occupy a more potent oral option if the safety and adherence profile holds up in broader use. The next clear milestone is Merck’s regulatory push, after the company said enlicitide received an FDA Commissioner’s National Priority Voucher in December 2025.