Obicetrapib on top of maximally tolerated lipid‐modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN
Year: 2024
Type: article
Abstract: BACKGROUND: Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events. METHODS AND RESULTS: BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a), and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2,532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024. CONCLUSION: These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.
Source: American Heart Journal
Authors: Stephen J. 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, Danielle Curcio, Erin Wuerdeman, Annie Neild, Douglas Kling, Andrew Hsieh, Mary R. Dicklin, Brian A. Ference, Ulrich Laufs, Maciej Banach, Roxana Mehran, Alberico L. Catapano, Michael H. Davidson
Institutions: Monash University, NewAmsterdam Pharma (Netherlands), Baylor College of Medicine, Imperial College London, The University of Texas Southwestern Medical Center, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Washington University in St. Louis, University of British Columbia, Centre for Heart Lung Innovation, University of Cambridge, University Hospital Leipzig, Leipzig University, Medical University of Lodz, Icahn School of Medicine at Mount Sinai, University of Milan, MultiMedica
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,950
OpenAlex ID: W4396639677