Recent lipoprotein(a) trials
Trent L. Wei, Leslie Cho
Abstract
PURPOSE OF REVIEW: Lipoprotein(a) (Lp(a)) is a genetically determined independent risk factor for cardiovascular disease and calcific aortic stenosis; thus, serum levels are minimally affected by conventional treatments for hypercholesterolemia and hypertriglyceridemia. New RNA therapies directly targeting Lp(a) have demonstrated efficacy in decreasing serum levels. Several recent trials have demonstrated efficacy and safety of these RNA therapeutics. RECENT FINDINGS: Single-stranded antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) are two classes of RNA-targeted therapeutics that specifically target the LPA gene, which encodes for apolipoprotein(a), a dominant and rate-limiting component in the hepatic synthesis of Lp(a) particle. Pelacarsen (ASO), olpasiran (siRNA) and SLN360 (siRNA) are novel drugs that have demonstrated efficacy in lowering Lp(a) levels and excellent safety profiles. SUMMARY: Lp(a) is an independent risk factor for cardiovascular disease. RNA-directed therapies, pelacarsen, olpasiran and SLN360, have shown efficacy in dramatically lowering serum Lp(a) levels. Outcomes data will be the next frontier of Lp(a) trials.