# Olpasiran

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**Olpasiran** (development code **AMG 890**, formerly ARO-LPA[1]) is an investigational [small interfering RNA](/source/Small_interfering_RNA) (siRNA) therapy developed by [Arrowhead Pharmaceuticals](/source/Arrowhead_Pharmaceuticals) and licensed worldwide by [Amgen](/source/Amgen). As of October 2025, it is in [phase 3](/source/Phases_of_clinical_research) trials to evaluate whether it reduces cardiovascular risk by lowering [lipoprotein(a)](/source/Lipoprotein(a)) (Lp(a)).[2] Olpasiran is under investigation to reduce major adverse cardiovascular events in patients with established [atherosclerotic](/source/Atherosclerosis) 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](/source/Adverse_event) were injection-site reactions,[4] which were usually mild.[5] No major safety signals emerged.[6]

## Mechanism of action

Olpasiran is a [N-acetylgalactosamine](/source/N-Acetylgalactosamine) (GalNAc)–[conjugated](/source/Bioconjugation) siRNA.[5] After uptake by [hepatocytes](/source/Hepatocyte) through the [asialoglycoprotein](/source/Asialoglycoprotein) receptor,[7] the [antisense](/source/Antisense_RNA) strand is incorporated into the [RNA-induced silencing complex](/source/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](/source/Double-stranded_RNA) 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](/source/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](/source/Dose%E2%80%93response_relationship), 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]

## References

1. ["Olpasiran - Amgen"](https://adisinsight.springer.com/drugs/800052678). *AdisInsight*. Retrieved 3 November 2025.

1. Dimitriadis, Kyriakos; Kyriakoulis, Konstantinos G.; Pyrpyris, Nikolaos; Beneki, Eirini; Kamperidis, Vasileios; Kollias, Anastasios; Cenko, Edina; Aznaouridis, Konstantinos; Aggeli, Konstantina; Tsioufis, Konstantinos (2025). "Lipoprotein(a) and aortic stenosis: Practical insights". *Nutrition, Metabolism and Cardiovascular Diseases*. **35** (10). [doi:10.1016/j.numecd.2025.104124](https://doi.org/10.1016/j.numecd.2025.104124). [hdl:11585/1047525](https://hdl.handle.net/11585/1047525). [PMID 40425406](https://pubmed.ncbi.nlm.nih.gov/40425406)

1. o'Donoghue, Michelle L.; Rosenson, Robert S.; López, J. Antonio G.; Lepor, Norman E.; Baum, Seth J.; Stout, Elmer; Gaudet, Daniel; Knusel, Beat; Kuder, Julia F.; Murphy, Sabina A.; Wang, Huei; Wu, You; Shah, Trupti; Wang, Jingying; Wilmanski, Tomasz; Sohn, Winnie; Kassahun, Helina; Sabatine, Marc S. (2024). "The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering". *Journal of the American College of Cardiology*. **84** (9): 790–797. [doi:10.1016/j.jacc.2024.05.058](https://doi.org/10.1016/j.jacc.2024.05.058). [PMID 39168564](https://pubmed.ncbi.nlm.nih.gov/39168564)

1. De Los Reyes, Chris; Rikhi, Rishi Raj; Doherty, Sean; Hernandez, Sebastian; Mirzai, Saeid; Shapiro, Michael D.; Christof, Michael; McIntosh, Scott; Wong, Nathan D.; Block, Robert C. (2025). "Current Clinical Trials for Treating Elevated Lipoprotein(a)". *Current Cardiovascular Risk Reports*. **19** (1). [doi:10.1007/s12170-025-00759-8](https://doi.org/10.1007/s12170-025-00759-8). [PMC 12282488](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282488). [PMID 40703143](https://pubmed.ncbi.nlm.nih.gov/40703143)

1. Górecka, Wiktoria; Berezovska, Daria; Mrozińska, Monika; Nowicka, Grażyna; Czerwińska, Monika E. (2025). "Biological and Biosimilar Medicines in Contemporary Pharmacotherapy for Metabolic Syndrome". *Pharmaceutics*. **17** (6): 768. [doi:10.3390/pharmaceutics17060768](https://doi.org/10.3390/pharmaceutics17060768). [PMC 12196407](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196407). [PMID 40574081](https://pubmed.ncbi.nlm.nih.gov/40574081)

1. Almaadawy, Omar; Hesn, Mohamed Mar'ey; Elsalamony, Yomna Ayman; Abobakr, Omar Ayman; Elshimy, Abdelrahman Hossam; Abulkhair, Khaled Alsayed; Negm, Mahmoud Mohamed; Shaban, Ahmed Yasser; Bene-Alhasan, Yakubu; Annie, Frank; Belcher, Adam; Elashery, Ahmed Ramy (2025). "Small interfering RNA effect on lipoprotein(a): A systematic review". *The Egyptian Heart Journal*. **77** (1). [doi:10.1186/s43044-025-00635-1](https://doi.org/10.1186/s43044-025-00635-1). [PMC 12062474](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062474). [PMID 40338464](https://pubmed.ncbi.nlm.nih.gov/40338464)

1. Ramírez-Cortés, Fabricio & Ménová, Petra (2025). "Hepatocyte targeting *via* the asialoglycoprotein receptor". *RSC Medicinal Chemistry*. **16** (2): 525–544. [doi:10.1039/d4md00652f](https://doi.org/10.1039/d4md00652f). [PMC 11609720](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609720). [PMID 39628900](https://pubmed.ncbi.nlm.nih.gov/39628900)

1. Bayer, Max (9 November 2022). ["Arrowhead fills quiver with $250M Royalty deal"](https://www.fiercebiotech.com/biotech/royalty-pharma-doles-out-250-million-royalty-rights-arrowheads-prized-amgen-partnered-heart). *Fierce Biotech*. Retrieved 3 November 2025.

1. Pagliarulo, Ned (9 November 2022). ["Arrowhead capitalizes on Amgen drug progress with royalty rights deal | BioPharma Dive"](https://www.biopharmadive.com/news/arrowhead-royalty-pharma-olpasiran-lpa-rights/636118/). *Biopharma Dive*. Retrieved 3 November 2025.

1. Cinezan, Corina; Magureanu, Dan Claudiu; Hiceag, Maria Luiza; Rus, Camelia Bianca; Ilias, Ioana Tiberia; Bogdan, Iulia Denisa; Buzle, Alexandra Manuela; Cozma, Angela (2025). "Shared Risk Factors and Molecular Mechanisms Between Aortic Stenosis and Atherosclerosis: A Rationale for Therapeutic Repositioning". *International Journal of Molecular Sciences*. **26** (17): 8163. [doi:10.3390/ijms26178163](https://doi.org/10.3390/ijms26178163). [PMC 12428528](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12428528). [PMID 40943088](https://pubmed.ncbi.nlm.nih.gov/40943088)

1. Pagliarulo, Ned. ["Amgen to test new way to lower heart risk with large drug trial | BioPharma Dive"](https://www.biopharmadive.com/news/amgen-olpasiran-lipoprotein-a-heart-phase-3/635875/). *Biopharma Dive*. Retrieved 3 November 2025.

1. Malick, Waqas A.; Goonewardena, Sascha N.; Koenig, Wolfgang; Rosenson, Robert S. (2023). "Clinical Trial Design for Lipoprotein(a)-Lowering Therapies". *Journal of the American College of Cardiology*. **81** (16): 1633–1645. [doi:10.1016/j.jacc.2023.02.033](https://doi.org/10.1016/j.jacc.2023.02.033)

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Adapted from the Wikipedia article [Olpasiran](https://en.wikipedia.org/wiki/Olpasiran) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Olpasiran?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.