{"id":"eca7b993b33b","type":"article","url":"https://hartvaat.nl/2026/01/13/enlicitide-orale-pcsk9-remmer-bij-heterozygote-fh-fase-3/","title":"Enlicitide: orale PCSK9-remmer bij heterozygote FH — fase 3","title_en":"Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["enlicitide","pcsk9-remmers","pcsk9-remmers-nieuwe-generatie"],"journal":"JAMA","doi":"10.1001/jama.2025.20620","source_url":"https://doi.org/10.1001/jama.2025.20620","authors":["Christie M Ballantyne","Laura Gellis","Jean-Claude Tardif","Puja Banka","Ann Marie Navar","Emil Andreas Asprusten","Russell Scott","Erik S G Stroes","Samar Froman","Geraldine Mendizabal","Fan Wang","Alberico L Catapano"],"significance":9,"published":"2026-01-13","source_date":"2026-01-13","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/"],"congress":"","summary_en":"This phase 3 trial demonstrated that enlicitide, an oral PCSK9 inhibitor, significantly reduced LDL cholesterol in adults with heterozygous familial hypercholesterolemia. An oral daily tablet offers a practical alternative to injectable PCSK9-lowering therapies for patients with genetic hypercholesterolemia.","created":"2026-07-03T10:32:07Z","updated":"2026-07-03T13:31:05Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Fase 3 trial van enlicitide, een orale PCSK9-remmer, bij heterozygote FH. Het middel verlaagde LDL significant en biedt een dagelijks oraal alternatief voor injecteerbare PCSK9-remmers.","abstract_original":"IMPORTANCE: Persons with heterozygous familial hypercholesterolemia (HeFH) are at increased risk of atherosclerotic cardiovascular disease due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C). Many patients with HeFH do not achieve guideline-recommended LDL-C goals with the currently available lipid-lowering therapies. OBJECTIVE: To evaluate the efficacy of enlicitide decanoate (an oral proprotein convertase subtilisin/kexin type 9 inhibitor) vs placebo in adults with HeFH requiring further lowering of LDL-C levels despite use of statin therapy. DESIGN, SETTING, AND PARTICIPANTS: This phase 3, randomized clinical trial included persons aged 18 years or older with HeFH currently using lipid-lowering therapy (taking at least a moderate- or high-intensity statin) and either an LDL-C level of 55 mg/dL or greater and a history of major atherosclerotic cardiovascular disease or an LDL-C level of 70 mg/dL or greater without a history of major atherosclerotic cardiovascular disease. The trial was conducted at 59 sites across 17 countries; the first participant was screened on August 8, 2023, and the last follow-up visit occurred on April 7, 2025. INTERVENTIONS: Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the mean percentage change in LDL-C level at week 24. The secondary outcomes included the mean percentage change in LDL-C level at week 52, the mean percentage change at week 24 in levels of non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, and the median percentage change at week 24 in lipoprotein(a). RESULTS: Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial. The mean LDL-C level was 119.0 mg/dL (SD, 41.0 mg/dL) at baseline, all had statin current use (81.5% were taking a high-intensity statin), and 64.4% were taking ezetimibe. 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). 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). 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), 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), 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). The incidence of adverse events, serious adverse events, and study discontinuation due to adverse events was similar between groups. CONCLUSIONS: 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). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05952869."}