Olpasiran
Investigational medical therapy
From Wikipedia, the free encyclopedia
Olpasiran (development code AMG 890, formerly ARO-LPA[1]) is an investigational small interfering RNA (siRNA) therapy developed by Arrowhead Pharmaceuticals and licensed worldwide by Amgen. As of October 2025[update], it is in phase 3 trials to evaluate whether it reduces cardiovascular risk by lowering lipoprotein(a) (Lp(a)).[2] Olpasiran is under investigation to reduce major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD) and elevated Lp(a) concentrations, as well as for individuals at high-risk for a first cardiovascular event and elevated Lp(a) concentrations.[3]
Adverse effects
In clinical trials, olpasiran was generally well tolerated. The most frequent adverse events were injection-site reactions,[4] which were usually mild.[5] No major safety signals emerged.[6]
Mechanism of action
Olpasiran is a N-acetylgalactosamine (GalNAc)–conjugated siRNA.[5] After uptake by hepatocytes through the asialoglycoprotein receptor,[7] the antisense strand is incorporated into the RNA-induced silencing complex (RISC),[5] which inhibits expression of the LPA gene. This reduces apolipoprotein(a) production and lowers circulating Lp(a).[4]
Olpasiran is a double-stranded siRNA[7] chemically modified for stability and conjugated with GalNAc[2] to enable hepatocyte targeting.[7]
History
Olpasiran was originally developed by Arrowhead Pharmaceuticals (as ARO-LPA) and licensed to Amgen in 2016.[8] In 2022, Arrowhead sold a portion of its royalty rights to Royalty Pharma.[9]
Research
In a phase 1 trial, one dose of olpasiran led to lower Lp(a) levels sustained for up to 6 months.[4] The phase 2 OCEAN(a)-DOSE trial demonstrated dose-dependent, sustained Lp(a) lowering[2] with acceptable tolerability. In OCEAN(a)-DOSE, olpasiran reduced Lp(a) levels by more than 95% at some doses as compared to placebo,[4] with durable suppression persisting for up to 48 weeks after treatment discontinuation.[10] A large phase 3 cardiovascular outcomes trial began in 2022[11] to determine whether Lp(a) reduction with olpasiran decreases events in patients with established ASCVD and a history of cardiovascular events.[2][12]