{"id":"e76b126c623f","type":"article","url":"https://hartvaat.nl/2025/01/21/muvalaplin-orale-lp-a-verlaging-nejm-gerandomiseerde-trial/","title":"Muvalaplin: orale Lp(a)-verlaging — NEJM gerandomiseerde trial","title_en":"Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial.","category":"preventie","category_label":"Preventie","professions":["apotheker","cardioloog","internist"],"tags":["soul-trial"],"journal":"JAMA","doi":"10.1001/jama.2024.24017","source_url":"https://doi.org/10.1001/jama.2024.24017","authors":["Stephen J Nicholls","Wei Ni","Grace M Rhodes","Steven E Nissen","Ann Marie Navar","Laura F Michael","Axel Haupt","John H Krege"],"significance":10,"published":"2025-01-21","source_date":"2025-01-21","image":"","kennis":[],"congress":"","summary_en":"This randomized trial demonstrated that muvalaplin, the first oral lipoprotein(a) inhibitor, produced dose-dependent Lp(a) reductions of up to 85% with an acceptable safety profile. An oral Lp(a)-lowering agent could dramatically expand access to treatment compared with injectable alternatives like olpasiran and pelacarsen.","created":"2026-07-03T10:31:26Z","updated":"2026-07-03T13:30:27Z","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":"NEJM-trial van muvalaplin, de eerste orale Lp(a)-verlager, toonde dosisafhankelijke Lp(a)-reductie tot 85%. Een orale Lp(a)-verlager zou de toegankelijkheid revolutionair verbeteren vergeleken met injecteerbare siRNA's.","abstract_original":"IMPORTANCE: Muvalaplin inhibits lipoprotein(a) formation. A 14-day phase 1 study demonstrated that muvalaplin was well tolerated and reduced lipoprotein(a) levels up to 65%. The effect of longer administration of muvalaplin on lipoprotein(a) levels in individuals at high cardiovascular risk remains uncertain. OBJECTIVES: To determine the effect of muvalaplin on lipoprotein(a) levels and to assess safety and tolerability. DESIGN, SETTING, AND PARTICIPANTS: Phase 2, placebo-controlled, randomized, double-blind trial enrolling 233 participants with lipoprotein(a) concentrations of 175 nmol/L or greater with atherosclerotic cardiovascular disease, diabetes, or familial hypercholesterolemia at 43 sites in Asia, Europe, Australia, Brazil, and the United States between December 10, 2022, and November 22, 2023. INTERVENTIONS: Participants were randomized to receive orally administered muvalaplin at dosages of 10 mg/d (n = 34), 60 mg/d (n = 64), or 240 mg/d (n = 68) or placebo (n = 67) for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was the placebo-adjusted percentage change from baseline in lipoprotein(a) molar concentration at week 12, using an assay to measure intact lipoprotein(a) and a traditional apolipoprotein(a)-based assay. Secondary end points included the percentage change in apolipoprotein B and high-sensitivity C-reactive protein. RESULTS: The median age of study participants was 66 years; 33% were female; and 27% identified as Asian, 4% as Black, and 66% as White. Muvalaplin resulted in placebo-adjusted reductions in lipoprotein(a) of 47.6% (95% CI, 35.1%-57.7%), 81.7% (95% CI, 78.1%-84.6%), and 85.8% (95% CI, 83.1%-88.0%) for the 10-mg/d, 60-mg/d, and 240-mg/d dosages, respectively, using an intact lipoprotein(a) assay and 40.4% (95% CI, 28.3%-50.5%), 70.0% (95% CI, 65.0%-74.2%), and 68.9% (95% CI, 63.8%-73.3%) using an apolipoprotein(a)-based assay. Dose-dependent reductions in apolipoprotein B were observed at 8.9% (95% CI, -2.2% to 18.8%), 13.1% (95% CI, 4.4%-20.9%), and 16.1% (95% CI, 7.8%-23.7%) at 10 mg/d, 60 mg/d, and 240 mg/d, respectively. No change in high-sensitivity C-reactive protein was observed. No safety or tolerability concerns were observed at any dosage. CONCLUSIONS AND RELEVANCE: Muvalaplin reduced lipoprotein(a) measured using intact lipoprotein(a) and apolipoprotein(a)-based assays and was well tolerated. The effect of muvalaplin on cardiovascular events requires further investigation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05563246."}