Effect of Pelacarsen on Lipoprotein(a) Cholesterol and Corrected Low-Density Lipoprotein Cholesterol.

BACKGROUND

Laboratory methods that report low-density lipoprotein cholesterol (LDL-C) include both LDL-C and lipoprotein(a) cholesterol [Lp(a)-C] content.

OBJECTIVES

The purpose of this study was to assess the effect of pelacarsen on directly measured Lp(a)-C and LDL-C corrected for its Lp(a)-C content.

METHODS

The authors evaluated subjects with a history of cardiovascular disease and elevated Lp(a) randomized to 5 groups of cumulative monthly doses of 20-80 mg pelacarsen vs placebo. Direct Lp(a)-C was measured on isolated Lp(a) using LPA4-magnetic beads directed to apolipoprotein(a). LDL-C was reported as: 1) LDL-C as reported by the clinical laboratory; 2) LDL-C

RESULTS

The baseline median Lp(a)-C values in the groups ranged from 11.9 to 15.6 mg/dL. Compared with placebo, pelacarsen resulted in dose-dependent decreases in Lp(a)-C (2% vs -29% to -67%; P = 0.001-<0.0001). Baseline laboratory-reported mean LDL-C ranged from 68.5 to 89.5 mg/dL, whereas LDL-C

CONCLUSIONS

Pelacarsen significantly lowers direct Lp(a)-C and has neutral to mild lowering of LDL-C

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures The clinical trial was funded by Ionis Pharmaceuticals, and the direct Lp(a)-C measurements were funded by Novartis through a research grant to UCSD (to Dr Tsimikas). Drs Karwatowska-Prokopczuk and Xia are employees of Ionis Pharmaceuticals. Dr Witztum is a consultant to Ionis Pharmaceuticals. Drs Witztum and Tsimikas are coinventors and receive royalties from patents owned by UCSD on oxidation-specific antibodies and of biomarkers related to oxidized lipoproteins; and are cofounders and have an equity interest in Oxitope, Inc and its affiliates (“Oxitope”) as well as in Kleanthi Diagnostics, LLC (“Kleanthi”). The terms of this arrangement have been reviewed and approved by the University of California-San Diego in accordance with its conflict-of-interest policies. Dr Tsimikas is an employee of Ionis Pharmaceuticals and of the University of California-San Diego; and is a co-founder of Covicept Therapeutics and has received research support from the Fondation Leducq. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.