This data is for laboratory research purposes only. Not for human or animal consumption.
What is Enlicitide?
Enlicitide (developmental code MK-0616; marketed as Lipfendra) is a synthetic macrocyclic peptide developed by Merck that inhibits PCSK9, a liver protein that normally degrades LDL receptors and raises circulating LDL-cholesterol. Enlicitide is the first PCSK9 inhibitor formulated as a once-daily oral tablet — every prior FDA-approved PCSK9 inhibitor (evolocumab/Repatha, alirocumab/Praluent, inclisiran/Leqvio) requires subcutaneous injection.
Mechanism of Action
Enlicitide is an octapeptide built from two natural and six non-natural amino acids, assembled into three fused macrocyclic rings anchored by an ammonium-containing side chain. This macrocyclic architecture confers conformational rigidity and protease resistance, allowing the peptide to survive gastrointestinal transit and achieve oral bioavailability — an engineering feat historically limited to small molecules. Once absorbed, enlicitide binds PCSK9 with high affinity, blocking its interaction with the LDL receptor and preserving hepatic LDL receptor density, which increases clearance of circulating LDL-cholesterol.
Observed Clinical Results
- Phase 3 CORALreef Lipids (NEJM, Feb 2026; PMID 41879224; NCT05952856; n=2,904): 55.8% placebo-adjusted LDL-C reduction at week 24 in adults with or at high risk for atherosclerotic cardiovascular disease (ASCVD), with concordant reductions in non-HDL-C, apolipoprotein B, and lipoprotein(a); adverse event rates comparable to placebo.
- Phase 3 CORALreef HeFH (NCT05952869): 59% placebo-adjusted LDL-C reduction in adults with heterozygous familial hypercholesterolemia.
- CORALreef Outcomes (NCT06008756): Large cardiovascular morbidity/mortality outcomes trial, fully enrolled at over 14,500 participants as of mid-July 2026; results pending.
Regulatory Status
FDA Approved — Merck's Lipfendra (enlicitide) 20 mg tablets received FDA approval on July 16, 2026 as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia. Not a compounding-pharmacy peptide; enlicitide is a branded, orally dosed small-scale peptide therapeutic, not 503A-eligible.