Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a): A Randomized Dose-Ascending Clinical Trial
In phase 1 study (n=48, no CVD, lipoprotein(a) [Lp(a) ≥75 nmol/L), there was single serious ADR & dose-dependent reductions in serum Lp(a), with maximal median change from baseline ranging from −5% placebo & −41% up to – 97% in 4mg, 12mg, 32mg, 96mg, 304mg & 608mg dose groups.
Source:
JAMA Network Open
SPS commentary:
In the study at day 337, the median change in lipoprotein(a) was −94% in the 608-mg dose group. A Phase II study is underway.
Lepodisiran is a small interfering RNA (siRNA) therapeutic that works by targeting and disabling the mRNA molecule that encodes for apolipoprotein(a), which is a crucial component of Lp(a). It is designed to work in the liver and is attached to a sugar called GalNAc, which binds to its corresponding receptors found on hepatic cells.
A JAMA Insights article published in June explains how small interfering RNA can modulate disease targets considered “undruggable” by small molecules and biologics.