Enlicitide

Merck developed enlicitide as MK-0616 and markets it as Lipfendra. It blocks PCSK9, a protein regulating liver LDL clearance, in a peptide tablet taken once daily. This provides an oral approach to a target previously addressed by injected antibodies or RNA therapy.

PCSK9 normally binds hepatic LDL receptors and promotes their destruction. Enlicitide binds circulating PCSK9 and prevents that interaction, allowing more LDL receptors to recycle to the liver-cell surface and remove LDL from blood. Engineering a peptide sufficiently small and stable for oral administration distinguishes it from injectable PCSK9 medicines.

Multiple large Phase 3 studies reported LDL reductions of about 60%, in the range seen with injectable PCSK9 antibodies. LDL reduction and prevention of cardiovascular events are separate outcomes.

FDA approved enlicitide as Lipfendra in 2026 for LDL reduction in adults with hypercholesterolemia. It is taken once daily by mouth. At approval, a cardiovascular-outcomes trial was still investigating whether the cholesterol reduction translates to fewer heart attacks and strokes.

It is prescribed alongside diet and exercise for adult high LDL cholesterol, including heterozygous familial hypercholesterolemia (HeFH). Pivotal programs generally added it to existing treatment, often a statin, when further LDL lowering was needed. It offers a clinician-directed oral option for people who might otherwise require an injectable PCSK9 agent.

In CORALreef Lipids, overall adverse-event rates were similar to placebo. The HeFH trial reported dizziness in 9% versus 4% with placebo and diarrhea in 7% versus 2%. Adverse-event discontinuation proportions were similar in both major trials.

The prescribing information advises stopping when pregnancy is recognized unless expected benefits outweigh fetal risks. Individual medication interactions and risk assessment remain part of prescribing.