Evidence map›Paper›PMID 42550463›Full record

ArticleHepatology international2026

Bepirovirsen induces innate immune proteins independent of HBV.

Jared L Delahaye, Shihyun You, Kai Fu, Scott Van Buren, Cheng Zhu, William Jordan, Avijit Ray, Johannes M Freudenberg, Kristen M Consalvo, Luca Pagliaroli and 6 more

3 registry-linked trialsAbstract read
PubMed Publisher
In one paragraph

Article in Hepatology international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. 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.

NCT02981602 phase2completednot on this map

A Phase 2, Double-Blinded, Randomized, Placebo-Controlled, Dose-Escalation Study to Examine the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ISIS 505358 in Treatment-Naïve Patients With Chronic HBV Infection

TypeinterventionalSponsorGlaxoSmithKlineRan2017 to 2019Enrolled31ConditionsHepatitis B, Chronic Hepatitis B AtypicalArmsIONIS-HBVRx, Placebo
NCT06058390 phase1completednot on this map

A Phase 1, Randomized, Open-Label, Parallel Group Study to Evaluate the Relative Bioavailability of Subcutaneous Bepirovirsen When Delivered From a Vial or Prefilled Syringe Fitted With a Safety Syringe Device in Healthy Adult Participants

TypeinterventionalSponsorGlaxoSmithKlineRan2023 to 2024Enrolled160ConditionsHepatitis BArmsBepirovirsen
NCT06422767 phase1completednot on this map

A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Parallel Group Study to Evaluate the Effect of Bepirovirsen on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers

TypeinterventionalSponsorGlaxoSmithKlineRan2024 to 2025Enrolled46ConditionsHepatitis BArmsBepirovirsen, Placebo
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

16 authors.

Jared L DelahayeHBV/Virology Translational Science, GSK, Collegeville, PA, USA. jared.l.delahaye@gsk.com.ORCID http://orcid.org/0000-0002-6506-2208
Shihyun YouHBV Research, Collegeville, PA, USA.
Kai FuTranslational Omics, GSK, Collegeville, PA, USA.
Scott Van BurenTranslational Omics, GSK, Collegeville, PA, USA.
Cheng ZhuTranslational Omics, GSK, Waltham, MA, USA.
William JordanTranslational Omics, GSK, Collegeville, PA, USA.
Avijit RayHBV Research, Collegeville, PA, USA.
Johannes M FreudenbergTranslational Omics, GSK, Collegeville, PA, USA.
Kristen M ConsalvoCellular Biomarkers, GSK, Collegeville, PA, USA.
Luca PagliaroliCellular Biomarkers, GSK, Collegeville, PA, USA.
Sohil JoshiCellular Biomarkers, GSK, Collegeville, PA, USA.
Puneet DhawanCellular Biomarkers, GSK, Collegeville, PA, USA.
Dickens TheodoreClinical Development, GSK, Durham, NC, USA.
Melanie PaffMedical Development, GSK, Collegeville, PA, USA.
Jill WalkerHBV/Virology Translational Science, GSK, San Francisco, CA, USA.
Jennifer M SinghHBV/Virology Translational Science, GSK, Collegeville, PA, USA.

Funding

GSK 205695 [NCT02981602]GSK 205873 [NCT06422767]GSK 219239 [NCT06058390]
6 · The paper itself

Abstract

backgroundBepirovirsen, an antisense oligonucleotide that targets all hepatitis B virus (HBV) mRNAs, is in development for the treatment of chronic HBV infection. Clinical studies have demonstrated that bepirovirsen has multiple mechanisms of action, including lowering HBV DNA, reducing viral protein production, and inducing immune activation. Post hoc analysis of biomarker samples from three studies was performed to further characterize changes in soluble protein biomarkers after bepirovirsen dosing.

methodsAcross three studies (CS3 [NCT02981602] in participants with chronic HBV infection; PFS [NCT06058390] and QTc [NCT06422767] in healthy volunteers) participants received bepirovirsen (150 mg, 300 mg, or 450 mg) or placebo. Longitudinal serum samples were taken for exploratory proteomics analysis. Relative expression of soluble proteins, including immune-related biomarkers, was measured, and differential expression was determined across arms. Clustering analysis was performed to identify kinetic patterns.

resultsBepirovirsen induced significant, transient protein differential expression in the hours after dosing, while there were relatively minor changes in placebo. There were many similarities in protein biomarkers induced in CS3 participants with chronic HBV infection and in the two healthy volunteer studies. Additionally, bepirovirsen treatment increased abundance of many proteins to a higher degree with increasing dose.

conclusionsThese findings strengthen the association between bepirovirsen treatment and changes in innate immune-related proteins and indicate that this effect does not require the presence of HBV. The kinetic patterns of protein expression suggest that there are multiple waves of protein induction, which could impact recruitment and activation of innate and adaptive immune cell types. CLINICAL TRIAL NUMBER: NCT02981602, NCT06058390, NCT06422767.

Indexed as

Biomarker analysisChronic hepatitis BClustering analysisHBVImmune activationInnate immunityMechanism of actionPhase 1 studyPhase 2a studySoluble biomarkersUnconjugated antisense oligonucleotide

Identifiers

What OpenQuestion holds

Textmetadata
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.