TY - JOUR
T1 - Obicetrapib
T2 - Reversing the Tide of CETP Inhibitor Disappointments
AU - Kastelein, John J. P.
AU - Hsieh, Andrew
AU - Dicklin, Mary R.
AU - Ditmarsch, Marc
AU - Davidson, Michael H.
N1 - Funding Information: J.J.P.K, A.H., M.D., and M.H.D. are employees of NewAmsterdam Pharma and they also report that they receive stock or stock options. J.J.P.K is the Chief Scientific Officer of NewAmsterdam Pharma. A.H. is the Executive Director, R&D, NewAmsterdam Pharma. M.D. is the Chief Development Officer of NewAmsterdam Pharma. M.H.D. is the Chief Executive Officer of NewAmsterdam Pharma. M.R.D., as an employee of Midwest Biomedical Research, is a consultant for NewAmsterdam Pharma. In addition, M.R.D., as an employee of Midwest Biomedical Research, reports the following companies contracted consulting and/or research with their institution and it received the consulting fees and grant funding from Acasti Pharma, Beren Therapeutics, Eli Lilly and Company, Indiana University and Foundation, Matinas BioPharma, NewAmsterdam Pharma, and 89Bio. Funding Information: This manuscript was funded by NewAmsterdam Pharma, Naarden, Netherlands. Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Purpose of Review: To discuss the history of cardiovascular outcomes trials of cholesteryl ester transfer protein (CETP) inhibitors and to describe obicetrapib, a next-generation, oral, once-daily, low-dose CETP inhibitor in late-stage development for dyslipidemia and atherosclerotic cardiovascular disease (ASCVD). Recent Findings: Phase 1 and 2 trials have evaluated the safety and lipid/lipoprotein effects of obicetrapib as monotherapy, in conjunction with statins, on top of high-intensity statins (HIS), and with ezetimibe on top of HIS. In ROSE2, 10 mg obicetrapib monotherapy and combined with 10 mg ezetimibe, each on top of HIS, significantly reduced low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total LDL particles, small LDL particles, small, dense LDL-C, and lipoprotein (a), and increased HDL-C. Phase 3 pivotal registration trials including a cardiovascular outcomes trial are underway. Summary: Obicetrapib has an excellent safety and tolerability profile and robustly lowers atherogenic lipoproteins and raises HDL-C. As such, obicetrapib may be a promising agent for the treatment of ASCVD.
AB - Purpose of Review: To discuss the history of cardiovascular outcomes trials of cholesteryl ester transfer protein (CETP) inhibitors and to describe obicetrapib, a next-generation, oral, once-daily, low-dose CETP inhibitor in late-stage development for dyslipidemia and atherosclerotic cardiovascular disease (ASCVD). Recent Findings: Phase 1 and 2 trials have evaluated the safety and lipid/lipoprotein effects of obicetrapib as monotherapy, in conjunction with statins, on top of high-intensity statins (HIS), and with ezetimibe on top of HIS. In ROSE2, 10 mg obicetrapib monotherapy and combined with 10 mg ezetimibe, each on top of HIS, significantly reduced low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total LDL particles, small LDL particles, small, dense LDL-C, and lipoprotein (a), and increased HDL-C. Phase 3 pivotal registration trials including a cardiovascular outcomes trial are underway. Summary: Obicetrapib has an excellent safety and tolerability profile and robustly lowers atherogenic lipoproteins and raises HDL-C. As such, obicetrapib may be a promising agent for the treatment of ASCVD.
KW - Atherosclerotic cardiovascular disease (ASCVD)
KW - Cardiovascular outcomes trial
KW - Cholesteryl ester transfer protein (CETP) inhibitor
KW - High-density lipoprotein cholesterol (HDL-C)
KW - Low-density lipoprotein cholesterol (LDL-C)
KW - Obicetrapib
UR - http://www.scopus.com/inward/record.url?scp=85180237979&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s11883-023-01184-1
DO - https://doi.org/10.1007/s11883-023-01184-1
M3 - Review article
C2 - 38133847
SN - 1523-3804
JO - Current Atherosclerosis Reports
JF - Current Atherosclerosis Reports
ER -