Prevention & lipidsRandomised controlled trial
Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia
- Randomised controlled trial
- phase 3
- 2:1 randomisation
- 59 sites across 17 countries
First participant screened August 8, 2023; last follow-up April 7, 2025
Authors' conclusion
Among adults with HeFH, treatment with enlicitide was well tolerated and significantly reduced levels of LDL-C, apolipoprotein B, non-HDL-C, and lipoprotein(a).
Study context
- Population
- Adults with heterozygous familial hypercholesterolemia (HeFH) on at least moderate- or high-intensity statin needing further LDL-C lowering (LDL-C ≥55 mg/dL with major atherosclerotic CVD history or ≥70 mg/dL without)293 (96.7%) completed
- Participants
- 303 adults
- Comparison
- Enlicitide vs placebo
- Enlicitiden = 202
- Placebon = 101reference
- Primary endpoint
- Mean percentage change in LDL-C
- Follow-up
- Week 24
Primary result
Mean % change in LDL-C
Between-group difference
−59.4 %
95% CI −65.6% to −53.2%
P < 0.001
By group
Enlicitide
−58.2
mean percentage change · %
Placebo
2.6
mean percentage change · %
Enlicitide vs Placebo
between-group difference −59.4 % (95% CI −65.6% to −53.2%); P < 0.001
As reported in the abstract
Secondary outcomes
| Outcome | Enlicitide | Placebo | between-group difference (%) (95% CI) | P value | |
|---|---|---|---|---|---|
| Mean % change in LDL-C · week 52 | mean percentage change −55.3 % | mean percentage change 8.7 % | −61.5 (−69.4% to −53.7%) | P < 0.001 | |
| Mean % change in non-HDL-C · week 24 | mean percentage change −52.3 % | mean percentage change 2.1 % | −53.0 (−58.5% to −47.4%) | P < 0.001 | |
| Mean % change in apolipoprotein B · week 24 | mean percentage change −48.2 % | mean percentage change 1.8 % | −49.1 (−54.0% to −44.3%) | P < 0.001 | |
| Median % change in lipoprotein(a) · week 24 | median percentage change −24.7 % | median percentage change −1.6 % | −27.5 (−34.3% to −20.6%) | P < 0.001 | |
| −100−50050Difference, % (linear scale) |
Safety
Adverse events, serious adverse events, discontinuation due to adverse events
- Incidence similar between groups
Original publication
Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia. JAMA. Published 13 January 2026. doi:10.1001/jama.2025.20620
Summarised from the published abstract; every number is checked against it