JAMA
AHA 2025: Oral PCSK9 inhibitor lowers cholesterol by ~60% in familial hypercholesterolemia
Enlicitide, an oral PCSK9 inhibitor, reduced LDL-C by up to 60% and could eventually offer an option for patients whose LDL levels remain above goal despite lifestyle changes and standard cholesterol medications. These findings were presented at the American Heart Association's 2025 Scientific Sessions.
Study details: The phase 3, randomized, placebo-controlled CORALree Lipids trial (NCT05952869) enrolled adults with genetically confirmed heterozygous familial hypercholesterolemia (HeFH) taking at least moderate- or high-intensity statin therapy. Participants were randomized (2:1) to receive 20 mg oral enlicitide once daily (n=202) or placebo (n=101) for 52 weeks. Primary endpoint: percent change in LDL‑C at week 24. Secondary outcomes included LDL‑C at week 52 and levels of non-HDL‑C, apolipoprotein B, and lipoprotein(a).
Results: Among the 303 randomized participants (mean age, 52.4 years; 51% female), 96.7% completed the trial. Baseline LDL‑C averaged 119 mg/dL; all were on statins (81.5% high-intensity) and 64.4% used ezetimibe. At week 24, LDL‑C fell by 58.2% with enlicitide vs. a 2.6% increase with placebo (between-group difference, −59.4%; 95% confidence interval [CI], −65.6 to −53.2; P<.001), and by week 52, reductions remained robust (−55.3% vs. 8.7%; difference −61.5%; P<.001). Non-HDL‑C dropped by 52.3%, apolipoprotein B by 48.2%, and lipoprotein(a) by 24.7% compared with minimal changes the placebo group (all P<.001). Adverse events, serious events, and discontinuations were similar between groups, with no new safety signals observed.
Source:
Ballantyne CM, et al. (2025, November 9). JAMA. Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/41206969/