Oral inhibition
Nicholls and colleagues review muvalaplin, the first oral Lp(a)-lowering agent, as it enters cardiovascular outcome testing (Curr Opin Lipidol 2024)
Original title: Oral agents for lowering lipoprotein(a)
This review traces the development of oral agents to lower Lp(a), a field until now dominated by injectable RNA-targeted therapies that inhibit apo(a) synthesis. Muvalaplin is the first orally administered, small-molecule Lp(a) inhibitor in clinical development, working by disrupting the binding between apo(a) and apoB rather than blocking apo(a) production. Nonhuman primate studies and early human trials have shown muvalaplin produces dose-dependent Lp(a) lowering. With no Lp(a)-lowering therapy yet approved, the authors note ongoing clinical trials will need to determine both muvalaplin's effect in high cardiovascular risk populations and, ultimately, whether it reduces cardiovascular events, the open question that will decide its clinical value.
Original abstract
Purpose Of Review: To review the development of oral agents to lower Lp(a) levels as an approach to reducing cardiovascular risk, with a focus on recent advances in the field.
Recent Findings: Extensive evidence implicates Lp(a) in the causal pathway of atherosclerotic cardiovascular disease and calcific aortic stenosis. There are currently no therapies approved for lowering of Lp(a). The majority of recent therapeutic advances have focused on development of injectable agents that target RNA and inhibit synthesis of apo(a). Muvalaplin is the first, orally administered, small molecule inhibitor of Lp(a), which acts by disrupting binding of apo(a) and apoB, in clinical development. Nonhuman primate and early human studies have demonstrated the ability of muvalaplin to produce dose-dependent lowering of Lp(a). Ongoing clinical trials will evaluate the impact of muvalaplin in high cardiovascular risk and will ultimately need to determine whether this strategy lowers the rate of cardiovascular events.
Summary: Muvalaplin is the first oral agent, developed to lower Lp(a) levels. The ability of muvalaplin to reduce cardiovascular risk remains to be investigated, in order to determine whether it will be a useful agent for the prevention of cardiovascular disease.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.