TY - JOUR
T1 - Clinical Trial Design for Lipoprotein(a)-Lowering Therapies
T2 - JACC Focus Seminar 2/3
AU - Malick, Waqas A.
AU - Goonewardena, Sascha N.
AU - Koenig, Wolfgang
AU - Rosenson, Robert S.
N1 - Funding Information:
The authors acknowledge the efforts of all the physicians and faculty who participated in the Cardiovascular Clinical Trials Forum Atherosclerosis Sessions 2021 and made this paper possible.
Publisher Copyright:
© 2023 American College of Cardiology Foundation
PY - 2023/4/25
Y1 - 2023/4/25
N2 - Lipoprotein(a) [Lp(a)] is a source of residual risk in patients with atherosclerotic cardiovascular disease (ASCVD). Clinical trials of fully human monoclonal antibodies targeting proprotein convertase subtilisin kexin 9 have shown that reductions in Lp(a) concentrations may be a predictor of event reduction with this class of cholesterol-lowering therapy. With the advent of selective therapies targeting Lp(a) such as antisense oligonucleotides, small-interfering RNA–based therapies, and gene editing, lowering of Lp(a) may lead to reduction in ASCVD. The phase 3 Lp(a)HORIZON (Assessing the Impact of Lipoprotein(a) Lowering with TQJ230 on Major Cardiovascular Events in Patients With CVD) outcomes trial is currently testing the effect of pelacarsen, an antisense oligonucleotide, on ASCVD risk. Olpasiran is a small-interfering RNA that is in a phase 3 clinical trial. As these therapies enter clinical trials, challenges in trial design will have to be addressed to optimize patient selection and outcomes.
AB - Lipoprotein(a) [Lp(a)] is a source of residual risk in patients with atherosclerotic cardiovascular disease (ASCVD). Clinical trials of fully human monoclonal antibodies targeting proprotein convertase subtilisin kexin 9 have shown that reductions in Lp(a) concentrations may be a predictor of event reduction with this class of cholesterol-lowering therapy. With the advent of selective therapies targeting Lp(a) such as antisense oligonucleotides, small-interfering RNA–based therapies, and gene editing, lowering of Lp(a) may lead to reduction in ASCVD. The phase 3 Lp(a)HORIZON (Assessing the Impact of Lipoprotein(a) Lowering with TQJ230 on Major Cardiovascular Events in Patients With CVD) outcomes trial is currently testing the effect of pelacarsen, an antisense oligonucleotide, on ASCVD risk. Olpasiran is a small-interfering RNA that is in a phase 3 clinical trial. As these therapies enter clinical trials, challenges in trial design will have to be addressed to optimize patient selection and outcomes.
KW - Lp(a)
KW - Lp(a) clinical trials
KW - olpasiran
KW - pelacarsen
UR - http://www.scopus.com/inward/record.url?scp=85152115926&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2023.02.033
DO - 10.1016/j.jacc.2023.02.033
M3 - Review article
AN - SCOPUS:85152115926
SN - 0735-1097
VL - 81
SP - 1633
EP - 1645
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 16
ER -