TY - JOUR
T1 - Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins
T2 - a randomized phase 2 trial
AU - Nicholls, Stephen J.
AU - Ditmarsch, Marc
AU - Kastelein, John J.
AU - Rigby, Scott P.
AU - Kling, Douglas
AU - Curcio, Danielle L.
AU - Alp, Nicholas John
AU - Davidson, Michael H.
N1 - Funding Information:
This trial was funded by New Amsterdam Pharma. We thank the contributions of the study patients, the dedicated study physicians and the New Amsterdam Pharma operations team.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022/8
Y1 - 2022/8
N2 - Global guidelines for the management of high-cardiovascular-risk patients include aggressive goals for low-density lipoprotein cholesterol (LDL-C). Statin therapy alone is often insufficient to reach goals and nonstatin options have limitations. Here, we tested the lipid-lowering effects of the cholesteryl ester transfer protein (CETP) inhibitor drug obicetrapib in a randomized, double-blind, placebo-controlled trial in dyslipidaemic patients (n = 120, median LDL-C 88 mg dl−1) with background high-intensity statin treatment (NCT04753606). Over the course of 8 weeks, treatment with 5 mg or 10 mg obicetrapib resulted in a significant decrease as compared with placebo in median LDL-C concentration (by up to 51%; P < 0.0001), the primary trial outcome. As compared with placebo, obicetrapib treatment also significantly (P < 0.0001) decreased apolipoprotein B (by up to 30%) and non-high-density lipoprotein cholesterol (non-HDL-C) concentration (by up to 44%), and significantly (P < 0.0001) increased HDL-C concentration (by up to 165%; the secondary trial outcomes) and had an acceptable safety profile. These results support the potential of obicetrapib to address an unmet medical need for high-cardiovascular-risk patients.
AB - Global guidelines for the management of high-cardiovascular-risk patients include aggressive goals for low-density lipoprotein cholesterol (LDL-C). Statin therapy alone is often insufficient to reach goals and nonstatin options have limitations. Here, we tested the lipid-lowering effects of the cholesteryl ester transfer protein (CETP) inhibitor drug obicetrapib in a randomized, double-blind, placebo-controlled trial in dyslipidaemic patients (n = 120, median LDL-C 88 mg dl−1) with background high-intensity statin treatment (NCT04753606). Over the course of 8 weeks, treatment with 5 mg or 10 mg obicetrapib resulted in a significant decrease as compared with placebo in median LDL-C concentration (by up to 51%; P < 0.0001), the primary trial outcome. As compared with placebo, obicetrapib treatment also significantly (P < 0.0001) decreased apolipoprotein B (by up to 30%) and non-high-density lipoprotein cholesterol (non-HDL-C) concentration (by up to 44%), and significantly (P < 0.0001) increased HDL-C concentration (by up to 165%; the secondary trial outcomes) and had an acceptable safety profile. These results support the potential of obicetrapib to address an unmet medical need for high-cardiovascular-risk patients.
UR - https://www.scopus.com/pages/publications/85135835966
U2 - 10.1038/s41591-022-01936-7
DO - 10.1038/s41591-022-01936-7
M3 - Article
C2 - 35953719
AN - SCOPUS:85135835966
SN - 1078-8956
VL - 28
SP - 1672
EP - 1678
JO - Nature Medicine
JF - Nature Medicine
IS - 8
ER -