Novel Therapeutics for Reduction of Lipoprotein (a)

  Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. Traditional lipid-lowering therapies have minimal impact on Lp(a), necessitating novel treatments. Zerlasiran, a small-interfering RNA (siRNA), significantly reduces Lp(a) (~85%) by inhibiting hepatic apolipoprotein(a) synthesis via subcutaneous injection. Muvalaplin, an oral small-molecule inhibitor, prevents Lp(a) particle formation, reducing levels by up to 85.8%. Both drugs were well-tolerated in Phase 2 trials, with further studies needed to evaluate cardiovascular event reduction.