Alirocumab decreases plasma Lp(a) levels without enhancing Lp(a) liver uptake in vivo

Aim: Lipoprotein (a) [Lp(a)], a causal cardiovascular risk factor, was resistant to SoC lipid lowering therapies until advent of new drugs like PCSK9 mAbs (e.g. alirocumab). The mechanisms by which PCSK9 modulates Lp(a) metabolism remain controversial. We have previously shown that physiological levels of PCSK9 do not alter Lp(a) uptake in primary human hepatocytes but rather increase apo(a) secretion. We also showed that alirocumab decreases the production rate of apolipoprotein (a) in non-human primates. Here, we aimed to ascertain whether PCSK9 blockade alters liver uptake of Lp(a) using humanized-liver mice (FRG® - Yecuris).