---
title: "Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Expected outcomes of therapy"
description: "Formulary evidence on Hibsago (bepirovirsen, GSK3228836) in Chronic hepatitis B virus infection in adults without cirrhosis: Expected outcomes of therapy. Topics: Treatment endpoints: functional and partial cure definitions, Expected characteristics of functional and partial cure: 2022 definitions, Treatment goals beyond liver outcomes: AASLD/IDSA 2025 guideline, Clinical outcomes after HBsAg loss: EASL 2025 evidence review, and 6 further topics. 10 evidence topics quoted from 11 sources."
canonical: "https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/product-information-and-disease-description/expected-outcomes-of-therapy"
published: "2026-10-21T22:39:04-04:00"
modified: "2026-10-22T19:07:03-04:00"
---

# Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Expected outcomes of therapy

<a id="heading-2.2.2.7"></a>

## 2.2.2.7 Expected Outcomes of Therapy

<a id="topic-2.2.2.7-1"></a>

### Treatment endpoints: functional and partial cure definitions

> “The recommended endpoint of novel therapy is functional cure defined as HBsAg loss using a conventional assay for detection of HBsAg (limit of detection 0.05 IU/mL) and HBV DNA below the lower limit of quantification (i.e. < 10 IU/ml) at 24 weeks off-therapy.”
> “An intermediate endpoint on the pathway to functional cure is partial cure, defined as HBsAg <100 IU/ml and HBV DNA below the lower limit of quantification (i.e. < 10 IU/ml) at 24 weeks off- treatment. However, further clinical data are needed to establish that HBsAg decline to <100 IU/ml is a clinically meaningful threshold suitable for use as part of composite clinical trial endpoint.”
> “The panel continues supporting the recommendation that anti-HBs is not required for definition of functional cure, as HBsAg loss is maintained in over 90% of patients with or without anti-HBs in long-term follow-up with currently approved therapies but will need to be confirmed with therapies in development.”

Source: [Ghany et al. (2023)](https://pmc.ncbi.nlm.nih.gov/articles/PMC12373085/)

<a id="topic-2.2.2.7-2"></a>

### Expected characteristics of functional and partial cure: 2022 definitions

| Characteristic | Functional cure (2022 definition) | Partial cure (2022 definition) |
| --- | --- | --- |
| HBsAg levels, IU/ml | “<LLOQ” | “<100” |
| HBV DNA levels, IU/ml | “<LLOQ” | “< LLOQ” |
| Clinical outcomes | “Improved” | “Improved” |
| Residual risk of HCC | “Very low” | “Very low” |
| Durability over time | “Yes” | “Yes” |
| Stigma for HBV | “No” | “Yes” |

Source: [Ghany et al. (2023)](https://pmc.ncbi.nlm.nih.gov/articles/PMC12373085/)

<a id="topic-2.2.2.7-3"></a>

### Treatment goals beyond liver outcomes: AASLD/IDSA 2025 guideline

> “Other goals of antiviral therapy include reduction in onward transmission (both vertical (mother-to-child) and horizontal (e.g., sexual, parenteral, nosocomial)), improvement in patient reported outcomes and quality of life as well as decreased stigma.”

Source: [Ghany et al. (2026)](https://doi.org/10.1097/HEP.0000000000001549)

<a id="topic-2.2.2.7-4"></a>

### Clinical outcomes after HBsAg loss: EASL 2025 evidence review

> “In Asian studies, loss of HBsAg has been associated with a lower risk of HCC, especially when it occurs before the age of 50, compared to individuals who do not achieve HBsAg loss.”
> “A systematic review also showed that HBsAg loss correlates with lower rates of incident cirrhosis, hepatic decompensation, and overall and liver-related mortality, though there was substantial heterogeneity across studies for all outcomes.”
> “An additional benefit of HBsAg loss is the possibility of discontinuing NA therapy.”
> “A recent study has highlighted the importance of functional cure, which is rarely achieved with current therapies, in reducing social stigma and self-stigma and significantly improving the HRQoL of individuals living with HBV.”

Source: [EASL (2025)](https://doi.org/10.1016/j.jhep.2025.03.018)

<a id="topic-2.2.2.7-5"></a>

### Durability of HBsAg loss and hepatocellular carcinoma incidence: meta-analysis

> “Thirty‐eight studies and 43,924 patients were finally included. The results showed that HBsAg seroclearance was durable, with a pooled recurrence rate of 6.19% (95% CI: 4.10%–8.68%).”
> “Anti‐HBs seroconversion resulted in a significantly reduced recurrence rate (RR = 0.25, p < .001). Patients who experienced HBsAg seroclearance had significantly lower HCC incidence than HBsAg‐positive (RR = 0.41, p < .001). The pooled HCC incidence after HBsAg seroclearance was 1.88%; this rate was reduced to 0.76% among patients without baseline cirrhosis.”

Source: [Song et al. (2021)](https://pmc.ncbi.nlm.nih.gov/articles/PMC7986681/)

<a id="topic-2.2.2.7-6"></a>

### HBsAg loss and clinical outcomes in a U.S. cohort

> “In total, 15,760 patients with chronic HBV infection were included; 5.6% were receiving stable antiviral treatment. Overall, 4.2% (n = 667) experienced HBsAg loss across the study period. HBsAg loss was associated with an 89% and 62% reduced risk of hepatocellular carcinoma (HCC; adjusted hazard ratio [aHR]: 0.11, 95% CI: 0.01–0.76) and all‐cause mortality (ACM; aHR: 0.38, 95% CI: 0.20–0.74), respectively. Risks of compensated cirrhosis (aHR: 0.84, 95% CI: 0.52–1.35) and decompensated liver disease (aHR: 0.74, 95% CI: 0.37–1.48) were lower after HBsAg loss, but did not reach significance.”

Source: [Drysdale et al. (2026)](https://pmc.ncbi.nlm.nih.gov/articles/PMC13179525/)

<a id="topic-2.2.2.7-7"></a>

### Residual hepatocellular carcinoma risk after HBsAg loss

> “For individuals who have cleared HBsAg, one study reported an annual HCC incidence of 0.86% overall, 2.42% in those with cirrhosis, 0.43% in those without cirrhosis, 1.07% for males, 0.57% for females, 1.21% if ≥50 years, and 0.33% if <50 years”
> “In a meta-analysis of 24 studies of 33,838 persons who cleared HBsAg, the pooled proportions of HCC occurrence ranged from 0.35% to 0.78% per year following treatment-induced or spontaneous HBsAg loss, respectively.”

Source: [Ghany et al. (2026)](https://doi.org/10.1097/HEP.0000000000001549)

> “Although progression of liver disease to cirrhosis or hepatic decompensation generally stops when patients lose HBsAg unless other causes of liver injury are present (eg, heavy alcohol consumption or nonalcoholic fatty liver), the risk of HCC persists, particularly if HBsAg loss occurred in patients older than 50 years or in those with cirrhosis or coinfection with HCV or hepatitis D virus (HDV) (128, 130–132).”

Source: [Terrault et al. (2018)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5975958/)

<a id="topic-2.2.2.7-8"></a>

### Bepirovirsen: expected off-treatment response and durability through week 96

> “At Week 72, 24 weeks after stopping NrtI therapy, 79% (233/295) of these participants met the primary endpoint. Of the 233 participants who met the primary endpoint at Week 72, 91% (211/233) maintained response off all HBV treatment at Week 96.”
> “Through Week 96, among the 84 HIBSAGO recipients who discontinued NrtI therapy but did not achieve the primary endpoint at Week 72 (62 participants) or who achieved the primary endpoint but did not maintain a sustained response at Week 96 (22 participants), one participant met criteria to restart NrtI therapy.”
> “Out of the 84 participants, three additional participants restarted NrtI therapy within one month of NrtI cessation without having met the protocol-defined NrtI restart criteria.”

Source: [Hibsago prescribing information (2026)](https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Hibsago/pdf/HIBSAGO-PI-MG-IFU.PDF)

<a id="topic-2.2.2.7-9"></a>

### Bepirovirsen: proportion able to stop existing therapy and off-treatment control

> “Across the two trials, 24% of patients who received Hibsago met the requirements to stop their existing medicine, compared with none who received placebo. Twenty-four weeks after stopping all hepatitis B treatment, 19% of patients who received Hibsago still had the virus under control, and a protein that signals hepatitis B infection (HBsAg) could not be detected in their blood.”

Source: [FDA Hibsago approval announcement (2026)](https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-chronic-hepatitis-b-treatment)

<a id="topic-2.2.2.7-10"></a>

### Bepirovirsen: HBsAg reduction to 100 IU/mL or less at week 72

> “Exploratory analyses also showed bepirovirsen reduced HBsAg to ≤100 IU/ml in 49% of participants (598 of 1220) in the overall study population, and in 62% of bepirovirsen recipients in the ≤1000 IU/ml (476 of 768) sub-group”

Source: [GSK press release, Hibsago US approval (2026)](https://www.gsk.com/en-gb/media/press-releases/hibsago-bepirovirsen-approved-in-the-us-for-the-treatment-of-chronic-hepatitis-b-chb/)

Additional sources: [Lok (2026)](https://pubmed.ncbi.nlm.nih.gov/42206569/); [Kim et al. (2014)](https://pubmed.ncbi.nlm.nih.gov/24162593/)

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