Pelacarsen

Yeang C, et al. Journal of the American College of Cardiology, 2022, 79(11), 1035-1046.

Pelacarsen targets apolipoprotein(a) to selectively reduce lipoprotein(a) [Lp(a)] cholesterol levels, addressing a significant risk factor in cardiovascular disease (CVD). Elevated Lp(a) is associated with atherosclerosis and thrombotic events, making its reduction a critical therapeutic goal.
In a clinical trial, pelacarsen was administered in cumulative monthly doses ranging from 20 to 80 mg to patients with CVD and elevated Lp(a). The study utilized advanced magnetic bead technology (LPA4) for direct measurement of Lp(a)-C and introduced corrected low-density lipoprotein cholesterol (LDL-Ccorr) to accurately isolate LDL-C changes from Lp(a)-C interference.
Pelacarsen demonstrated a dose-dependent reduction in Lp(a)-C, with decreases ranging from 29% to 67% compared to placebo (P ≤ 0.0001). Correspondingly, laboratory-reported LDL-C levels were reduced by 7% to 26%, while LDL-Ccorr showed a neutral to mild decrease of 2% to 19% (P = 0.05-0.95). Total apolipoprotein B (apoB) levels were reduced by 3% to 16%, reflecting a broader impact on atherogenic lipoproteins. However, non-Lp(a) apoB levels remained unchanged, indicating pelacarsen's selective action on Lp(a).
By mitigating Lp(a)-C while maintaining or slightly reducing corrected LDL-C, pelacarsen offers a precise intervention for patients with Lp(a)-driven cardiovascular risk. The study highlights the superiority of LDL-Ccorr over traditional laboratory-reported LDL-C in assessing lipid changes during therapy.