Safety and Efficacy of Obicetrapib in Patients With Heterozygous Familial Hypercholesterolemia
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Pharmacologic Therapy BROOKLYN examined the efficacy, safety, and tolerability of obicetrapib 10 mg, as an adjunct to maximally tolerated lipid-modifying therapies, in patients with heterozygous familial hypercholesterolemia (HeFH) and suboptimal LDL-C control. This was a phase 3, randomized, double-blind, placebo-controlled trial NCT05425745 with 1 year follow up in 354 patients across 70 sites. Participants (n=354) with HeFH and fasting LDL-C ³70 mg/dL taking maximally tolerated lipid-modifying therapies were randomly assigned to receive obicetrapib 10 mg or matching placebo orally daily for 52 weeks in a 2:1 ratio. Study primary endpoint assessed obicetrapib compared with placebo in LS mean percent change from baseline to week 12 in LDL-C. Secondary endpoints included obicetrapib compared with placebo in percent changes from baseline in Apo B, nonHDL-C, HDL-C, total-C, Lp(a), and TG, and safety measures; Apo A1 was an exploratory endpoint. Mean baseline lipoprotein lipid levels for obicetrapib and placebo, respectively, were LDL-C: 123.4 and 119.9 mg/dL; ApoB: 107.2 and 105.3 mg/dL; non-HDL-C: 148.4 and 146.7 mg/dL; and HDL-C: 53.2 and 50.2 mg/dL. Obicetrapib, compared with placebo, significantly reduced mean LDL-C -36.3% at day 84 (P<0.0001) and -41.5% at day 365 (P<0.0001). On day 84 and day 365, obicetrapib, compared with placebo, significantly reduced mean ApoB -24.4%, -25.8%; non-HDL-C -34.5%, -37.5%; Lp(a) -45.9%, -54.3%; and increased HDL-C 138.7%,121.4%, respectively. Obicetrapib was well tolerated with no serious adverse events or clinically significant changes in vital signs, electrocardiograms, or other clinical laboratory values. Obicetrapib, as an adjunct to maximally tolerated lipid-modifying therapies, produced significant LDL-C lowering at day 84 with sustained effect through day 365 in patients with HeFH. Obicetrapib holds promise for patients with HeFH who are unable to attain their LDL-C treatment targets with available lipid-lowering agents.
Authors: Andy Hsieh, Stephen Nicholls, Adam J Nelson, Marc Ditmarsch, John J.P. Kastelein, Christie M. Ballantyne, Kausik K. Ray, Ann Marie Navar, Steven E. Nissen, Anne C. Goldberg, Liam R. Brunham, Erin Wuerdeman, Annie Neild, Douglas Kling, Brian A. Ference, Ulrich Laufs, Maciej Banach, Roxana Mehran, Alberico L. Catapano, Michael H. Davidson
Institutions: NewAmsterdam Pharma (Netherlands), Monash University, Baylor College of Medicine, Imperial College London, The University of Texas Southwestern Medical Center, Cleveland Clinic, Washington University in St. Louis, University of British Columbia, Menarini Group (Italy), Fondazione Internazionale Menarini, University Hospital Leipzig, Medical University of Lodz, University of Milan
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,900
OpenAlex ID: W4414439823