Bepirovirsen induces innate immune proteins independent of HBV
Hepatology International, 2026
Delahaye J., You S., Fu K., Van Buren S., Zhu C., Jordan W., Ray A., Freudenberg J., Consalvo K., Pagliaroli L., Joshi S., Dhawan P., Theodore D., Paff M., Walker J., Singh J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma Serum |  Olink Explore 3072/384 |
Abstract
Background
Bepirovirsen, 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.
Methods
Across 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.
Results
Bepirovirsen 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.
Conclusions
These 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.
Graphical Abstract
Bepirovirsen induces proteomic changes consistent with a transient innate immune response in healthy volunteers and participants with chronic HBV infection