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FDA approval · Merck · Cardiology

Lipfendraenlicitide

FDA approves the first oral PCSK9 inhibitor to lower LDL cholesterol in adults.

CompareMerck press release
FDA approval · New moleculeFirst oral PCSK9 inhibitor40-second read

Lipfendraenlicitide

Merck · Oral PCSK9 inhibitor (macrocyclic peptide) · Cardiology

Bottom line for your patients

Adults who need more LDL-C lowering now have a PCSK9 inhibitor taken as a daily pill. Whether it reduces cardiovascular events has not been shown yet.

Drug brief
Drug IQ
Who it is for
Adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia, as an adjunct to diet and exercise to reduce LDL-C.
What changes
Merck describes it as the first oral PCSK9 inhibitor approved to reduce LDL-C. Both pivotal trials compared it with placebo in patients on stable lipid-lowering treatment, and patients taking PCSK9 inhibitors were excluded from CORALreef Lipids.
The evidence
In CORALreef Lipids, LDL-C fell 56% compared to placebo at week 24 (95% CI: -61, -51; p<0.001). In CORALreef HeFH, LDL-C fell 59% compared to placebo at week 24 (95% CI: -66, -53; p<0.001).Placebo-controlled randomized trialCORALreef Lipids (2,904 patients) and CORALreef HeFH (303 patients) · Phase 3Randomized against placebo: shows that it works, not how it compares with existing treatments.
Watch for
In CORALreef HeFH, diarrhea (7% vs 2% with placebo) and dizziness (9% vs 4%) were the most common adverse reactions occurring more often than with placebo. It is not yet known if Lipfendra can reduce the risk of cardiovascular morbidity and mortality.
How it is given
Oral20 mg tablet once daily
What the approval tells you
New molecule. An active ingredient the FDA had not approved before.

Clinical summary

Lipfendra is a once-daily 20 mg oral PCSK9 inhibitor approved as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia. At week 24 it reduced LDL-C by 56% compared to placebo in CORALreef Lipids (2,904 patients) and by 59% in CORALreef HeFH (303 patients). It is not yet known whether it reduces cardiovascular morbidity and mortality; an outcomes trial is ongoing.

From the source 10

Merck press release

The Merck press release's own words, quoted exactly. Each line is what a claim on this page was checked against.

  1. RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has approved LIPFENDRA® (enlicitide) tablets 20 mg as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH).

    Backs · Indication, 20 mg tablets, first oral PCSK9 inhibitor

  2. LIPFENDRA is the first oral PCSK9 inhibitor approved to reduce LDL-C and is a novel macrocyclic peptide that inhibits the binding of PCSK9 to LDL receptors.

    Backs · First oral PCSK9 inhibitor approved to reduce LDL-C

  3. A statistically significant and clinically meaningful reduction in LDL-C of 56% compared to placebo at week 24 (95% CI: -61, -51; p<0.001), with a reduction from baseline (primary endpoint) in LDL-C of 57% for LIPFENDRA compared to an increase of 3% for placebo;

    Backs · 56% vs placebo at week 24, CI and p value

View all 10 lines

  1. A statistically significant and clinically meaningful reduction in LDL-C of 59% compared to placebo (95% CI: -66, -53; p<0.001), with a reduction from baseline (primary endpoint) in LDL-C of 58% for LIPFENDRA compared to an increase of 3% for placebo;

    Backs · 59% vs placebo at week 24, CI and p value

  2. CORALreef Lipids (NCT05952856) was a Phase 3, multicenter, double-blind, randomized, placebo-controlled study in which 2,904 patients with hypercholesterolemia (including those with and without HeFH) and a history of a major ASCVD event or increased risk for development of a first major ASCVD event were randomized in a 2:1 ratio to receive LIPFENDRA 20 mg orally once daily (n=1,935) or placebo (n=969) for 52 weeks.

    Backs · 2,904 patients, Phase 3, once daily, PCSK9 inhibitors excluded

  3. Patients taking PCSK9 inhibitors were excluded from the trial.

    Backs · PCSK9 inhibitor users excluded

  4. CORALreef HeFH (NCT05952869) was a Phase 3, multicenter, double-blind, randomized, placebo-controlled study in which 303 patients with HeFH were randomized in a 2:1 ratio to receive LIPFENDRA 20 mg orally once daily (n=202) or placebo (n=101) for 52 weeks.

    Backs · 303 patients in CORALreef HeFH

  5. In the CORALreef HeFH trial the most common adverse reactions that occurred at higher frequencies compared to placebo were diarrhea (LIPFENDRA 7%, placebo 2%) and dizziness (LIPFENDRA 9%, placebo 4%).

    Backs · Diarrhea 7% vs 2%, dizziness 9% vs 4%

  6. It is not yet known if LIPFENDRA can reduce the risk of cardiovascular morbidity and mortality.

    Backs · Cardiovascular outcomes unknown

  7. 26.Lipfendraenlicitide decanoate7/15/2026To reduce low-density lipoprotein cholesterol

    Backs · Action date 2026-07-15 (from FDA Novel Drug Approvals for 2026 table, not the Merck release, which is dated July 16, 2026)

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