ArticleClinical pharmacology in drug development2022
Preclinical and Phase 1 Assessment of Antisense Oligonucleotide Bepirovirsen in Hepatitis B Virus-Transgenic Mice and Healthy Human Volunteers: Support for Clinical Dose Selection and Evaluation of Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses.
Article in Clinical pharmacology in drug development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
What it found
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Safety, pharmacokinetics and antiviral activity of AHB‑137 in healthy volunteers and chronic hepatitis B patients: a phase 1a/1b study.Hepatology international · 2026Trial
- Comparison of Pharmacokinetics of the GalNAc-Conjugated Antisense Oligonucleotide GSK3389404 in Participants with Chronic Hepatitis B Infection across the Asia-Pacific Region.Antimicrobial agents and chemotherapy · 2023Trial
- Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies.Molecular therapy. Nucleic acids · 2026Review
- Decoding the Structural Complexity of Viral RNAs with SHAPE to Guide Antiviral Therapeutics.Viruses · 2026Review
- PBPK Modelling of Antisense Oligonucleotide Therapeutics: Application for Predicting Plasma and Tissue Pharmacokinetics of Bepirovirsen.The AAPS journal · 2026Article
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- [Clinical research advances for small-molecule nucleic acid drugs in the treatment of chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Lack of Pharmacokinetic Drug-Drug Interactions Between Bepirovirsen and Nucleos(t)ide Analogs.Clinical pharmacology in drug development · 2025Article
- Small nucleic acid drugs-the dawn of functional cure of chronic hepatitis B.Frontiers in pharmacology · 2025Review
- Population Pharmacokinetics of Bepirovirsen in Healthy Participants and Participants with Chronic Hepatitis B Virus Infection: Results from Phase 1, 2a, and 2b Studies.Infectious diseases and therapy · 2024Article
- Classifying hepatitis B therapies with insights from covalently closed circular DNA dynamics.Virologica Sinica · 2024Review
- Localization of unlabeled bepirovirsen antisense oligonucleotide in murine tissues using in situ hybridization and CARS imaging.RNA (New York, N.Y.) · 2023Article
- [Antisense oligodeoxynucleotides: the certain but limited efficacy and the uncovering mechanisms for the cure of chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dose-dependent reductions in hepatitis B virus (HBV) RNA, DNA, and viral proteins following bepirovirsen administration were observed in HepG2.2.15 cells. In HBV-transgenic mice treated at 50 mg/kg/wk, hepatic HBV RNA and DNA were reduced by 90% and 99%, respectively. Subsequently, a phase 1 first-in-human study assessed pharmacokinetics and tolerability of single (75-450 mg) and multiple (150-450 mg on days 1, 4, 8, 11, 15, and 22) subcutaneous bepirovirsen doses in 96 healthy volunteers. Bepirovirsen at all dose levels was rapidly absorbed (maximum plasma concentration 3-8 hours after dosing), rapidly distributed to peripheral tissues, and slowly eliminated (median plasma terminal half-life: 22.5-24.6 days across cohorts). Plasma exposure (dose-proportional at 150-450 mg) and concentration-time profiles were similar following the first and sixth doses, suggesting little to no plasma accumulation (steady state achieved by day 22). Renal elimination of full-length bepirovirsen accounted for <2% of the total dose. Across the single and multiple dose cohorts, 197 treatment-emergent adverse events were reported, with 99% and 65% classified as mild in severity and local injection site reactions, respectively. In conclusion, bepirovirsen showed an acceptable safety profile in humans with observed pharmacokinetics consistent with the chemical class, warranting further evaluation of bepirovirsen in chronic HBV infection.
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What OpenQuestion holds
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.