Muvalaplin cut Lp(a) by up to 85.5% on a novel intact assay in the phase 2 KRAKEN trial, review of the first oral Lp(a) inhibitor finds (Expert Opin Investig Drugs 2025)

Introduction: Lipoprotein(a) [Lp(a)] is an LDL-like particle, which is synthesized and assembled in the liver, and whose plasma levels are strongly associated with, and considered to be causative of, atherosclerotic cardiovascular disease (ASCVD). Several promising pharmacological therapies that directly target Lp(a) are under development.

Areas Covered: We discuss the role of Lp(a) in ASCVD, describe the pharmacodynamics, pharmacokinetics, and metabolism of muvalaplin, an oral Lp(a) inhibitor, as well as reporting on the findings of the phase II KRAKEN trial in adults at high cardiovascular risk with elevated Lp(a).

Expert Opinion: Muvalaplin is the first oral small molecule inhibitor of Lp(a) formation for the treatment of elevated Lp(a). In KRAKEN, muvalaplin significantly reduced Lp(a) levels in high-risk patients by up to 70% and 85.5% by traditional and novel isoform-insensitive intact assays, respectively. Safety and tolerability studies reported to date are promising, with minimal effect on plasminogen activity that was independent of dose. In terms of patient convenience and adherence, the oral dosing of muvalaplin may confer practical advantages over injectable Lp(a)-lowering therapies. The results of the MOVE-Lp(a) phase III trial, which is evaluating the effect of muvalaplin on cardiovascular outcomes in high-risk patients with elevated Lp(a), are eagerly awaited.