Evidence map›Paper›PMID 35027752›Full record

ArticleNature medicine2022

Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a).

Michael J Koren, Patrick Maurice Moriarty, Seth J Baum, Joel Neutel, Martha Hernandez-Illas, Howard S Weintraub, Monica Florio, Helina Kassahun, Stacey Melquist, Tracy Varrieur and 9 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03626662 (A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein), which is not on this map. Cited by 117 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03626662 phase1completednot on this map

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)

TypeinterventionalSponsorAmgenRan2018 to 2023Enrolled79ConditionsCardiovascular DiseaseArmsAMG 890, Placebo
3 · Its place in the literature

Who cites it

117 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Article
  7. Article
  8. Novel Lipoprotein (a) Therapies: A Comprehensive Review.Current atherosclerosis reports · 2026
    Review
  9. Article
  10. Old and New Lines of Therapy Targeting Lipoprotein(a).Current atherosclerosis reports · 2026
    Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Lowering of Lipoprotein(a) with Olpasiran.Cardiovascular & hematological disorders drug targets · 2026
    Review
  20. Lipoprotein(a) Lowering with Pelacarsen (TQJ230).Cardiovascular & hematological disorders drug targets · 2026
    Review

57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Michael J Koren *Jacksonville Center for Clinical Research, Jacksonville, FL, USA. mkoren@encoredocs.com.ORCID http://orcid.org/0000-0001-5023-7178
Patrick Maurice MoriartyUniversity of Kansas Medical Center, Kansas City, KS, USA.
Seth J BaumExcel Medical Clinical Trials, Boca Raton, FL, USA.
Joel NeutelOrange County Research Center, Tustin, CA, USA.
Martha Hernandez-IllasQPS MRA, Miami, FL, USA.
Howard S WeintraubNYU Langone Medical Center, New York, NY, USA.
Monica Florio *Amgen, Inc., Thousand Oaks, CA, USA.
Helina KassahunAmgen, Inc., Thousand Oaks, CA, USA.
Stacey MelquistArrowhead Pharmaceuticals, Inc, Pasadena, CA, USA.ORCID http://orcid.org/0000-0002-2974-9635
Tracy VarrieurAmgen, Inc., Cambridge, MA, USA.
Saptarsi M HaldarAmgen, San Francisco, CA, USA.
Winnie SohnAmgen, Inc., Thousand Oaks, CA, USA.
Huei WangAmgen, Inc., Thousand Oaks, CA, USA.
Mary Elliott-DaveyAmgen, Ltd., Cambridge, UK.
Brooke M RockAmgen, San Francisco, CA, USA.
Tao PeiArrowhead Pharmaceuticals, Inc., Madison, WI, USA.
Oliver HomannAmgen, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6550-1266
Jennifer HellawellAmgen, San Francisco, CA, USA.
Gerald F WattsUniversity of Western Australia and Royal Perth Hospital, Perth WA, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Compelling evidence supports a causal role for lipoprotein(a) (Lp(a)) in cardiovascular disease. No pharmacotherapies directly targeting Lp(a) are currently available for clinical use. Here we report the discovery and development of olpasiran, a first-in-class, synthetic, double-stranded, N-acetylgalactosamine-conjugated small interfering RNA (siRNA) designed to directly inhibit LPA messenger RNA translation in hepatocytes and potently reduce plasma Lp(a) concentration. Olpasiran reduced Lp(a) concentrations in transgenic mice and cynomolgus monkeys in a dose-responsive manner, achieving up to over 80% reduction from baseline for 5-8 weeks after administration of a single dose. In a phase 1 dose-escalation trial of olpasiran (ClinicalTrials.gov: NCT03626662 ), the primary outcome was safety and tolerability, and the secondary outcomes were the change in Lp(a) concentrations and olpasiran pharmacokinetic parameters. Participants tolerated single doses of olpasiran well and experienced a 71-97% reduction in Lp(a) concentration with effects persisting for several months after administration of doses of 9 mg or higher. Serum concentrations of olpasiran increased approximately dose proportionally. Collectively, these results validate the approach of using hepatocyte-targeted siRNA to potently lower Lp(a) in individuals with elevated plasma Lp(a) concentration.

Indexed as

Lipoprotein(a)RNA, Small InterferingAdultAnimalsFemaleHumansHyperlipidemiasMacaca fascicularisMaleMiceMice, TransgenicMiddle AgedLipoprotein(a)olpasiranRNA, Small Interfering

Identifiers

PMID35027752

What OpenQuestion holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.