Evidence mapPaperPMID 42137960Full record

Trial reportCirculation2026

Laroprovstat, the First Oral Small-Molecule PCSK9 Inhibitor for the Treatment of Hypercholesterolemia: Results From a Randomized, Single-Blind, Placebo-Controlled Phase 1 Trial in Treatment-Naïve Patients.

Rick B Vega, Gavin O'Mahony, April M Barbour, Hongtao Yu, Jane Knöchel, Johan Brengdahl, Thomas Hochdörfer, Linnéa Bergenholm, Eva Töppner Carlsson, Andrea Ahnmark and 19 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase I
In one paragraph

Trial report in Circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT05384262. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
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.

NCT05384262 phase1completed

A Phase I, Randomized, Single-Blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD0780 Following Single and Multiple Ascending Dose Administration to Healthy Subjects With or Without Elevated LDL-C Levels

Ran2022Enrolled183Registered outcomes10Posted comparisons0ConditionsDyslipidemiaArmsAZD0780, Placebo, Rosuvastatin
Open the trial in the graph
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Rick B VegaTranslational Science and Clinical Development, Cardiovascular, Renal and Metabolism (R.B.V.).
Gavin O'MahonyBiopharma Chemistry, Discovery Sciences (G.O.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0001-5944-1271
April M BarbourClinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences (A.M.B., H.Y.), AstraZeneca, Gaithersburg, MD.
Hongtao YuClinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences (A.M.B., H.Y.), AstraZeneca, Gaithersburg, MD.ORCID 0000-0003-2278-4478
Jane KnöchelClinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences (J.K.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Johan BrengdahlBioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (J.B.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Thomas HochdörferMechanistic Biology and Profiling, Discovery Sciences (T.H.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0002-9276-3114
Linnéa BergenholmDrug Metabolism, Pharmacokinetics and Biomarker Bioanalysis, Cardiovascular, Renal and Metabolism (L.B., A.B.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0002-4369-2903
Eva Töppner CarlssonBioscience Metabolism, Research & Early Development, Cardiovascular, Renal and Metabolism (E.T.C., A.A., D.L.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Andrea AhnmarkBioscience Metabolism, Research & Early Development, Cardiovascular, Renal and Metabolism (E.T.C., A.A., D.L.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Christina Rye UnderwoodBioscience Metabolism, Research and Early Development (C.R.U.), Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-2333-2177
Anna RudvikLate Cardiovascular, Renal and Metabolism (A.R.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Debra CarterGlobal Safety, Cardiovascular, Renal and Metabolism (D.C.), AstraZeneca, Gaithersburg, MD.
Johanna LaruPharmaceutical Sciences (J.L.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Aspen GutgsellProtein Science, Structure and Biophysics, Discovery Sciences, (A.G., S.G.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0003-1548-0169
Lee TwaddleEarly Phase Clinical Operations (L.T.), Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Pavlo GarkaviyEarly Clinical Development, Cardiovascular, Renal and Metabolism (P.G.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0009-0009-0511-9231
Anna BogstedtDrug Metabolism, Pharmacokinetics and Biomarker Bioanalysis, Cardiovascular, Renal and Metabolism (L.B., A.B.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Eva Hurt-CamejoTranslational Science and Clinical Development, Cardiovascular, Renal and Metabolism (E.H.-C., T.M., M.R. A.H., J.B.R.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Tasso MiliotisTranslational Science and Clinical Development, Cardiovascular, Renal and Metabolism (E.H.-C., T.M., M.R. A.H., J.B.R.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0003-4917-0724
Maria RyaboshapkinaTranslational Science and Clinical Development, Cardiovascular, Renal and Metabolism (E.H.-C., T.M., M.R. A.H., J.B.R.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0003-1385-8869
Andreas HoberTranslational Science and Clinical Development, Cardiovascular, Renal and Metabolism (E.H.-C., T.M., M.R. A.H., J.B.R.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0001-8947-2562
Brian HubbardDogma Therapeutics, Boxford, MA (B.H., M.S.-W., V.K.).
Michael Serrano-WuDogma Therapeutics, Boxford, MA (B.H., M.S.-W., V.K.).
Virendar KaushikDogma Therapeutics, Boxford, MA (B.H., M.S.-W., V.K.).ORCID 0009-0007-7116-4001
Stefan GeschwindnerProtein Science, Structure and Biophysics, Discovery Sciences, (A.G., S.G.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0002-2154-8345
Michael C McCarthyResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD (M.C.M.).
Daniel LindénBioscience Metabolism, Research & Early Development, Cardiovascular, Renal and Metabolism (E.T.C., A.A., D.L.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0003-4158-8018
Jaya B RosenmeierTranslational Science and Clinical Development, Cardiovascular, Renal and Metabolism (E.H.-C., T.M., M.R. A.H., J.B.R.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0009-0004-2401-0235

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is an effective therapy for reducing low-density lipoprotein (LDL) cholesterol (LDL-C) in adults with hyperlipidemia, including heterozygous familial hypercholesterolemia, thereby lowering cardiovascular risk. Current PCSK9 inhibitors are injectable therapies; no oral small-molecule PCSK9 inhibitor has yet been approved.

methodsLaroprovstat (AZD0780) is a novel small-molecule identified through structure-based design that binds to the PCSK9 C-terminal domain. The effects of laroprovstat on LDL receptor expression and LDL-C levels were assessed in vitro and in mice expressing human

resultsLaroprovstat does not inhibit the PCSK9-LDL receptor interaction but stabilizes the PCSK9 C-terminal domain, preventing lysosomal trafficking and degradation of LDL receptor. Laroprovstat increased LDL receptor expression and reduced LDL-C levels in mice expressing human

conclusionsLaroprovstat was well tolerated with no safety findings of concern and may be dosed with or without food. In treatment-naïve participants with hypercholesterolemia, combined rosuvastatin 20 mg and laroprovstat 30 mg treatment led to an 80% LDL-C reduction, supporting further development of laroprovstat as the first oral small-molecule PCSK9 inhibitor in patients with hypercholesterolemia. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05384262.

Indexed as

Anticholesteremic AgentsHypercholesterolemiaPCSK9 InhibitorsAdministration, OralAdultAnimalsCholesterol, LDLFemaleHumansMaleMiceMiddle AgedProprotein Convertase 9Receptors, LDLSingle-Blind MethodYoung AdultAnticholesteremic AgentsCholesterol, LDLPCSK9 InhibitorsPCSK9 protein, humanProprotein Convertase 9Receptors, LDLclinical trial, phase 1hypercholesterolemiaPCSK9 inhibitors

Identifiers

PMID42137960
PMCPMC13286119

What Socratic holds

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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 Socratic graph.