{"id":"76f023231f95","type":"article","url":"https://hartvaat.nl/2023/04/25/mk-0616-eerste-orale-pcsk9-remmer-in-fase-2b/","title":"MK-0616: eerste orale PCSK9-remmer in fase 2b","title_en":"Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["enlicitide","niet-statine-therapie","pcsk9-remmers","pcsk9-remmers-nieuwe-generatie"],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2023.02.018","source_url":"https://doi.org/10.1016/j.jacc.2023.02.018","authors":["Christie M Ballantyne","Puja Banka","Gustavo Mendez","Raymundo Garcia","Julio Rosenstock","Anthony Rodgers","Geraldine Mendizabal","Yale Mitchel","Alberico L Catapano"],"significance":9,"published":"2023-04-25","source_date":"2023-04-25","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/","https://hartvaat.nl/kennis/lipiden/ezetimib/"],"congress":"","summary_en":"This phase 2b trial of MK-0616, the first oral macrocyclic peptide PCSK9 inhibitor, demonstrated dose-dependent LDL cholesterol reductions of up to 60% with an acceptable safety profile. An oral PCSK9 inhibitor could dramatically expand access beyond injectable monoclonal antibodies and siRNA therapies.","created":"2026-07-03T10:30:21Z","updated":"2026-07-03T13:29:25Z","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 2b trial van MK-0616, de eerste orale PCSK9-remmer (macrocyclisch peptide), toonde dosisafhankelijke LDL-verlaging tot 60%. Een orale PCSK9-remmer zou de belangrijkste barrière voor breed gebruik wegnemen: de noodzaak van injecties.","abstract_original":"BACKGROUND: MK-0616 is an oral macrocyclic peptide inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) in development for the treatment of hypercholesterolemia. OBJECTIVES: This Phase 2b, randomized, double-blind, placebo-controlled, multicenter trial aimed to evaluate the efficacy and safety of MK-0616 in participants with hypercholesterolemia. METHODS: This trial was planned to include 375 adult participants with a wide range of atherosclerotic cardiovascular disease risk. Participants were assigned randomly (1:1:1:1:1 ratio) to MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo. The primary endpoints included percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 8 and the proportion of participants with adverse events (AEs) and study intervention discontinuations due to AEs; participants were monitored for AEs for an additional 8 weeks after the 8-week treatment period. RESULTS: Of the 381 participants randomized, 49% were female, and the median age was 62 years. Among 380 treated participants, all doses of MK-0616 demonstrated statistically significant (P < 0.001) differences in least squares mean percentage change in LDL-C from baseline to Week 8 vs placebo: -41.2% (6 mg), -55.7% (12 mg), -59.1% (18 mg), and -60.9% (30 mg). AEs occurred in a similar proportion of participants in the MK-0616 arms (39.5% to 43.4%) as placebo (44.0%). Discontinuations due to AEs occurred in 2 or fewer participants in any treatment group. CONCLUSIONS: MK-0616 demonstrated statistically significant and robust, dose-dependent placebo-adjusted reductions in LDL-C at Week 8 of up to 60.9% from baseline and was well tolerated during 8 weeks of treatment and an additional 8 weeks of follow-up. (A Study of the Efficacy and Safety of MK-0616 [Oral PCSK9 Inhibitor] in Adults With Hypercholesterolemia [MK-0616-008]; NCT05261126)."}