Enlicitide, the new drug that reduces LDL cholesterol: how it works

Encouraging data have emerged regarding a cholesterol-lowering pill called enlicitide decanoate . It is an oral inhibitor of Pcsk9 , a protein that regulates LDL cholesterol, taken once a day. The drug, as reported by Rainews.it , has significantly reduced LDL cholesterol in pivotal Phase 3 studies in adult patients with or at risk of atherosclerotic cardiovascular disease, and in patients with heterozygous familial hypercholesterolemia.

Enlicitide, the new drug that reduces LDL cholesterol

These are the results presented by MSD during the American Heart Association (AHA) Scientific Sessions 2025 , currently taking place in New Orleans . The next-generation molecule, designed to offer efficacy similar to that of monoclonal antibodies – MSD explains in a statement – ​​has “the potential to become the first approved oral PCSK9 inhibitor designed to reduce LDL-C , with a safety profile comparable to placebo.” The drug “aims to fill unmet therapeutic needs in the area of ​​atherosclerosis ,” one of the major causes behind the silent cardiovascular epidemic. "Enlicitide," explains Gaetano De Ferrari , principal investigator of the Coralreef Lipids study and director of Cardiology at the University of Turin , Molinette Hospital, "showed statistically significant and clinically relevant reductions in LDL cholesterol with a safety profile comparable to placebo, highlighting the revolutionary potential of the first oral Pcsk9 inhibitor. Despite the availability of lipid-lowering therapies such as statins and injectable Pcsk9 inhibitors, the majority of patients with atherosclerotic cardiovascular disease are unable to reduce their LDL cholesterol levels to the ideal threshold for their risk status."

An innovative approach and new therapeutic perspectives

" Enlicitide ," says Alberico Luigi Catapano , president of SISA, the Italian Society for the Study of Atherosclerosis , "represents an innovative approach to Pcsk9 inhibition in lipid-lowering therapy. It is the first oral macropeptide designed to offer the efficacy and specificity of anti-Pcsk9 monoclonal antibodies in a simple tablet, opening up new perspectives for the personalized treatment of patients at high cardiovascular risk. By blocking the interaction between the Pcsk9 protein and the LDL receptor, and therefore increasing the expression of the LDL receptor itself," the specialist emphasizes, "enlicitide increases the liver's ability to remove LDL from the blood, significantly and clinically reducing LDL cholesterol levels. This responds to a critical unmet clinical need, particularly (and not only) in patients with heterozygous familial hypercholesterolemia . This patient population is at high risk of premature atherosclerotic cardiovascular events, and a significant proportion do not reach the recommended LDL cholesterol levels." guidelines, despite available lipid-lowering therapies. Enlicitide could represent a therapeutic breakthrough for these patients."

The challenge of cardiovascular prevention

Cardiovascular events "in Italy reach a figure of approximately 230,000-240,000 per year, approximately 600 per day," says Pasquale Perrone Filardi , president of the Italian Society of Cardiology (SIC). " High cholesterol levels are a direct cause of heart attacks and strokes, but this awareness is not yet widespread enough. We must prevent the disease before it develops and treat it in its earliest stages. Enlicitide was designed to lower LDL cholesterol levels in the blood, offering the efficacy and specificity typical of anti-PCSK9 monoclonal antibodies in an easy-to-use tablet. It will add to the medical community's tools to address the unmet medical need for LDL cholesterol reduction, helping to improve outcomes for millions of people worldwide by modifying the natural progression of the disease ."