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.

Autor: Nicholls SJ; Victorian Heart Institute, Monash University, Victoria, Australia. Electronic address: stephen.nicholls@monash.edu., Nelson AJ; Victorian Heart Institute, Monash University, Victoria, Australia., Ditmarsch M; NewAmsterdam Pharma, Naarden, The Netherlands., Kastelein JJP; NewAmsterdam Pharma, Naarden, The Netherlands., Ballantyne CM; Baylor College of Medicine and the Texas Heart Institute, Houston, TX., Ray KK; Department of Primary Care and Public Health, Imperial College London, London, UK., Navar AM; University of Texas Southwestern Medical Center, Dallas, TX., Nissen SE; Cleveland Clinic Lerner School of Medicine at Case Western Reserve University, Cleveland, OH., Golberg AC; Washington University School of Medicine, St. Louis, MO., Brunham LR; UBC Centre for Heart Lung Innovation, The University of British Columbia, Vancouver, British Columbia, Canada., Curcio D; NewAmsterdam Pharma, Naarden, The Netherlands., Wuerdeman E; NewAmsterdam Pharma, Naarden, The Netherlands., Neild A; NewAmsterdam Pharma, Naarden, The Netherlands., Kling D; NewAmsterdam Pharma, Naarden, The Netherlands., Hsieh A; NewAmsterdam Pharma, Naarden, The Netherlands., Dicklin MR; Midwest Biomedical Research, Addison, IL., Ference BA; Centre for Naturally Randomized Trials, University of Cambridge, Cambridge, UK., Laufs U; Klinik und Poliklinkk für Kardiologie, Leipzig University, Germany., Banach M; Department of Preventive Cardiology and Lipidologym, Medical University of Lodz (MUL), Lodz, Poland., Mehran R; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Catapano AL; IRCCS MultiMedica, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy., Davidson MH; NewAmsterdam Pharma, Naarden, The Netherlands.
Jazyk: angličtina
Zdroj: American heart journal [Am Heart J] 2024 Aug; Vol. 274, pp. 32-45. Date of Electronic Publication: 2024 May 04.
DOI: 10.1016/j.ahj.2024.05.002
Abstrakt: 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.
Competing Interests: Conflict of interest Stephen J. Nicholls received grant/research support from AstraZeneca, New Amsterdam Pharma, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and was a consultant for AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, and Vaxxinity. Adam J. Nelson received personal fees from Boehringer Ingelheim, AstraZeneca, Amgen, Novartis, and Sanofi. Marc Ditmarsch is Chief Development Officer for NewAmsterdam Pharma. John J.P. Kastelein is Chief Scientific Officer for NewAmsterdam Pharma and Emeritus Professor of Medicine at the University of Amsterdam, The Netherlands. Christie M. Ballantyne received grant/research support (all paid to the institution, not individual) from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Regeneron, Roche Diagnostic, NIH, AHA, and ADA and was a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionia, Lilly, Matinas BioPharma Inc., Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostic. Kausik K. Ray reports his institution received unrestricted research grants from Amgen, Daiichi Sankyo, Regeneron, and Sanofi; consulting or advisory board honoraria from Novartis, Esperion, Daiichi Sankyo, Abbott, Bayer, Eli Lilly, Silence Therapeutics, CSL Behring, NewAmsterdam Pharma, Sanofi, Amgen Novo Nordisk, BI, Scribe, Vaxxinity, CRISPR, AZ, Kowa, and Cargene; honoraria for CME and non-CME from Novartis, Novo Nordisk, BI, AZ, Viatris, Daiichi Sankyo, Amgen, and Sanofi; and he has stock options from PEMI-31. Ann Marie Navar reports honoraria and consulting fees from AstraZeneca, Bayer, Bristol Meyer Squibb, Boehringer Ingelheim, Esperion, Janssen, Eli Lilly, Merck, NewAmsterdam Pharma, Novartis, NovoNordisk, Pfizer, and Silence Therapeutics; and funding for research to her institution from Esperion, Janssen, and Amgen. Steven E. Nissen reports that Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from Abbvie, AstraZeneca, Amgen, Arrowhead, Bristol Myers Squibb, Eli Lilly, Esperion, Medtronic, MyoKardia, NewAmsterdam Pharma, Novartis, Pfizer, and Silence Therapeutics. Dr. Nissen is involved in these clinical trials but receives no personal renumeration for his participation and consults for these pharmaceutical companies but does not accept compensation. Anne C. Goldberg has received research grant(s)/support from Amarin, Amgen, Akcea/IONIS, Arrowhead, Esperion Therapeutics, Inc., Merck, NewAmsterdam Pharma, Novartis, Pfizer, Regeneron, and Sanofi; has served as a consultant for 23andMe, Akcea, Esperion, IONIS, Merck, NewAmsterdam Pharma, Novartis, OptumRX, Regeneron, and Sanofi; and has provided editorial work for Merck. Liam R. Brunham is Reserch Chair, Associate Professor for The University of British Columbia. Danielle Curcio is Executive Director of Clinical Operations for NewAmsterdam Pharma. Erin Wuerdeman is Executive Director of Clinical Operations for NewAmsterdam Pharma. Annie Nield is Executive Vice President and Head of Global Regulatory Affairs for NewAmsterdam Pharma. Douglas Kling is Chief Operating Officer for NewAmsterdam Pharma. Andrew Hsieh is Vice President of Medical Affairs for NewAmsterdam Pharma. Mary R. Dicklin is an employee of Midwest Biomedical Research, which has received consulting fees and/or grant funding from NewAmsterdam Pharma, Acasti Pharma, Beren Therapeutics, Eli Lilly and Company, Indiana University and Foundation, Matinas BioPharma, NorthSea Therapeutics, and 89Bio. Brain A. Ference reports research grants from Merck, Novartis, Amgen, and Esperion Therapeutics, and consulting fees, advisory boards, or lecture honoraria from Novartis, Merck, Amgen, Regeneron, Sanofi, Novartis, Pfizer, Eli Lilly, Novo Nordisk, Daiichi-Sankyo, Viatris, Ionis Pharmaceuticals, NewAmsterdam Pharma, dalCOR, The Medicines Co., Mylan, CiVi Pharma, KrKa Pharmaceuticals, American College of Cardiology, EAS, and European Society of Cardiology. Ulrich Laufs has received honoraria from Amgen, Daiichi Sankyo, MSD, Novartis, and Sanofi. Maciej Banach has received renumeration for lectures from Adamed, Amgen, Daiichi Sankyo, Exceed Orphan, KRKA Polypharma, Mylan/Viatris, Novartis, Novo Nordisk, Pfizer, Sanofi, Teva, and Zentiva; participated in advisory panels for Adamed, Amgen, Daiichi Sankyo, Esperion, NewAmsterdam Pharma, Novartis, Novo Nordisk, and Sanofi; and received grants from Amgen, Daiichi Sankyo, Mylan/Viatris, and Sanofi. Roxana Mehran has institutional research grants from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Applied Therapeutics, Arena Pharmaceuticals, AstraZeneca, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, Cardiawav, CeloNova, Chiesi, Concept Medical, CSL Behring, CytoSorbents, Daiichi Sankyo, Element Science, Faraday Pharmaceuticals, Humacyte, Idorsia Pharmaceuticals, I-Laser, Janssen, Magenta Medical, Mediasphere Medical, Medtelligence, Medtronic, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Protembis, RenalPro, RM Global, Shockwave, Transverse Medical, Vivasure, and ZOLL Medical; consulting fees from AstraZeneca, Novartis, Cine-Med Research, Ionis Pharmaceuticals, Novo Nordisk, Vectura Inc., and WebMD; honoraria from Novartis Pharmaceuticals, Philips Electronics, Biotronik Inc., and Bayer Healthcare Pharmaceuticals; advisory board participation for Humacyte Inc., PhaseBio, Faraday Pharmaceuticals, Medtronic, Philips, and PLx Pharma; participation on a data safety monitoring board for Pi-Cardia; a leadership role with the American Medical Association (JAMA Cardiology, associate editor), American College of Cardiology (BOT Member, SC Member CTR Program), and Society for Cardiovascular Angiography & Interventions (Women in Innovations Committee Member); stock or stock options from Applied Therapeutics, Elixir Medical, Stel, and ControlRad; and faculty membership with the Cardiovascular Research Foundation. Alberico L. Catapano in the last three years has received honoraria, lecture fees, or research grants from Aegerion, Amarin, Amgen, Amryt Pharma, AstraZeneca, Daiichi Sankyo, Esperion, Ionis Pharmaceutical, Medscape Education, Menarini, MSD, NewAmsterdam Pharma, Novartis, NovoNordisk, PeerVoice, Pfizer, Recordati, Regeneron, Sanofi, The Corpus, Ultragenyx, and Viatris. Michael H. Davidson is Chief Executive Officer for NewAmsterdam Pharma.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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