Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial.

Ballantyne CM, Gellis L, Tardif JC, Banka P, Navar AM, Asprusten EA, Scott R, Stroes ESG, Froman S, Mendizabal G, Wang F, Catapano AL

JAMA1 Jan 2026Cited by 34 (Europe PMC)

PMID41206969PMCIDPMC12598580DOI10.1001/jama.2025.20620PepBankPUB-41206969

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with HeFH, enlicitide lowered LDL-C by 58.2% versus a 2.6% increase with placebo at week 24 (difference -59.4%; P<.001).
In plain wordsIn adults with inherited high cholesterol, enlicitide reduced LDL cholesterol more than placebo at week 24.
Peptide
Enlicitide
Outcome
DecreaseLDL-C change at week 24
Study
n = 303
Comparator
Placebo
Analysis
Primary
Outcome group
Lipids · Metabolic and weight
Studied dose
20 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
Mean percentage change in LDL-C
−58.2%
enlicitide group, week 24
Mean percentage change in LDL-C
2.6%
placebo group, week 24
Between-group difference in mean percentage change in LDL-C
−59.4%
enlicitide vs placebo, week 24
95% CI of between-group difference in LDL-C
−65.6 to −53.2%
enlicitide vs placebo, week 24
Source sentences
Summary
The mean percentage change in LDL-C level at week 24 was -58.2% in the enlicitide group vs 2.6% in the placebo group (between-group difference, -59.4% [95% CI, -65.6% to -53.2%]; P < .001).
2 context sentences(design, population, supporting numbers)
Summary · context
Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks.
Summary · context
Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial.
Report a problemFND-4120696901
02HumanRandomized controlled trialEfficacy outcome
In adults with HeFH, enlicitide lowered LDL-C by 55.3% versus an 8.7% increase with placebo at week 52 (difference -61.5%; P<.001).
In plain wordsIn adults with inherited high cholesterol, enlicitide reduced LDL cholesterol more than placebo at week 52.
Peptide
Enlicitide
Outcome
DecreaseLDL-C change at week 52
Study
n = 303
Comparator
Placebo
Analysis
Secondary
Outcome group
Lipids · Metabolic and weight
Studied dose
20 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
Mean percentage change in LDL-C
−55.3%
enlicitide group, week 52
Mean percentage change in LDL-C
8.7%
placebo group, week 52
Between-group difference in mean percentage change in LDL-C
−61.5%
enlicitide vs placebo, week 52
95% CI of between-group difference in LDL-C
−69.4 to −53.7%
enlicitide vs placebo, week 52
Source sentences
Summary
The mean percentage change in LDL-C level at week 52 was -55.3% in the enlicitide group vs 8.7% in the placebo group (between-group difference, -61.5% [95% CI, -69.4% to -53.7%]; P < .001).
2 context sentences(design, population, supporting numbers)
Summary · context
Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks.
Summary · context
Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial.
Report a problemFND-4120696902
03HumanRandomized controlled trialEfficacy outcome
In adults with HeFH, enlicitide lowered non-HDL-C by 52.3% versus a 2.1% increase with placebo (difference -53.0%; P<.001).
In plain wordsIn adults with inherited high cholesterol, enlicitide reduced non-HDL cholesterol more than placebo.
Peptide
Enlicitide
Outcome
DecreaseNon-HDL-C change at week 24
Study
n = 303
Comparator
Placebo
Analysis
Secondary
Outcome group
Lipids · Metabolic and weight
Studied dose
20 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
Mean percentage change in Non-HDL-C
−52.3%
enlicitide group, week 24
Mean percentage change in Non-HDL-C
2.1%
placebo group, week 24
Between-group difference in mean percentage change in Non-HDL-C
−53%
enlicitide vs placebo, week 24
95% CI of between-group difference in Non-HDL-C
−58.5 to −47.4%
enlicitide vs placebo, week 24
Source sentences
Summary
At week 24, the mean percentage change in non-HDL-C level was -52.3% in the enlicitide group vs 2.1% in the placebo group (between-group difference, -53.0% [95% CI, -58.5% to -47.4%]; P < .001),
2 context sentences(design, population, supporting numbers)
Summary · context
Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks.
Summary · context
Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial.
Report a problemFND-4120696903
04HumanRandomized controlled trialEfficacy outcome
In adults with HeFH, enlicitide lowered apolipoprotein B by 48.2% versus a 1.8% increase with placebo (difference -49.1%; P<.001).
In plain wordsIn adults with inherited high cholesterol, enlicitide reduced apolipoprotein B more than placebo.
Peptide
Enlicitide
Outcome
DecreaseApolipoprotein B change at week 24
Study
n = 303
Comparator
Placebo
Analysis
Secondary
Outcome group
Lipids · Metabolic and weight
Studied dose
20 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
Mean percentage change in Apolipoprotein B
−48.2%
enlicitide group, week 24
Mean percentage change in Apolipoprotein B
1.8%
placebo group, week 24
Between-group difference in mean percentage change in Apolipoprotein B
−49.1%
enlicitide vs placebo, week 24
95% CI of between-group difference in Apolipoprotein B
−54 to −44.3%
enlicitide vs placebo, week 24
Source sentences
Summary
the mean percentage change in apolipoprotein B level was -48.2% vs 1.8%, respectively (between-group difference, -49.1% [95% CI, -54.0% to -44.3%]; P < .001),
2 context sentences(design, population, supporting numbers)
Summary · context
Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks.
Summary · context
Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial.
Report a problemFND-4120696904
05HumanRandomized controlled trialEfficacy outcome
In adults with HeFH, the median lipoprotein(a) change was a 24.7% reduction with enlicitide versus a 1.6% reduction with placebo at week 24 (difference -27.5%; P<.001).
In plain wordsIn adults with inherited high cholesterol, enlicitide reduced lipoprotein(a) more than placebo.
Peptide
Enlicitide
Outcome
DecreaseLipoprotein(a) change at week 24
Study
n = 303
Comparator
Placebo
Analysis
Secondary
Outcome group
Lipids · Metabolic and weight
Studied dose
20 mg once daily · oral · 52 weeksAs given in this study (human).
Measurements
Median percentage change in Lipoprotein(a)
−24.7%
enlicitide group, week 24
Median percentage change in Lipoprotein(a)
−1.6%
placebo group, week 24
Between-group difference in median percentage change in Lipoprotein(a)
−27.5%
enlicitide vs placebo, week 24
95% CI of between-group difference in Lipoprotein(a)
−34.3 to −20.6%
enlicitide vs placebo, week 24
Source sentences
Summary
and the median percentage change in lipoprotein(a) level was -24.7% vs -1.6% (between-group difference, -27.5% [95% CI, -34.3% to -20.6%]; P < .001).
2 context sentences(design, population, supporting numbers)
Summary · context
Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks.
Summary · context
Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial.
Report a problemFND-4120696905
06HumanRandomized controlled trialSafety outcome
In adults with HeFH, adverse event incidence was similar with enlicitide and placebo.
In plain wordsIn adults with inherited high cholesterol, adverse event rates were similar with enlicitide and placebo.
Peptide
Enlicitide
Outcome
No significant changeAdverse events
Study
n = 303
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
20 mg once daily · oral · 52 weeksAs given in this study (human).
Source sentences
Summary
The incidence of adverse events, serious adverse events, and study discontinuation due to adverse events was similar between groups.
2 context sentences(design, population, supporting numbers)
Summary · context
Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks.
Summary · context
Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial.
Report a problemFND-4120696906
07HumanRandomized controlled trialSafety outcome
In adults with HeFH, serious adverse event incidence was similar with enlicitide and placebo.
In plain wordsIn adults with inherited high cholesterol, serious adverse event rates were similar with enlicitide and placebo.
Peptide
Enlicitide
Outcome
No significant changeSerious adverse events
Study
n = 303
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
20 mg once daily · oral · 52 weeksAs given in this study (human).
Source sentences
Summary
The incidence of adverse events, serious adverse events, and study discontinuation due to adverse events was similar between groups.
2 context sentences(design, population, supporting numbers)
Summary · context
Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks.
Summary · context
Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial.
Report a problemFND-4120696907
08HumanRandomized controlled trialSafety outcome
In adults with HeFH, discontinuation due to adverse events was similar with enlicitide and placebo.
In plain wordsIn adults with inherited high cholesterol, study discontinuation due to adverse events was similar with enlicitide and placebo.
Peptide
Enlicitide
Outcome
No significant changeDiscontinuation due to adverse events
Study
n = 303
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
20 mg once daily · oral · 52 weeksAs given in this study (human).
Source sentences
Summary
The incidence of adverse events, serious adverse events, and study discontinuation due to adverse events was similar between groups.
2 context sentences(design, population, supporting numbers)
Summary · context
Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks.
Summary · context
Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial.
Report a problemFND-4120696908

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT05952869

A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)

Merck Sharp & Dohme LLCn = 3038 Aug 2023 to 7 Apr 2025

Hypercholesterolemia · Familial Hypercholesterolemia

Trial page ClinicalTrials.govUpdated 24 Feb 2026

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

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