Triple Therapy More Than Doubles HBsAg Loss vs Peginterferon in HBV

A triple regimen of the investigational small interfering RNA (siRNA) elebsiran, the therapeutic vaccine BRII-179, and pegylated interferon alfa (PEG-IFNα) more than doubled the rate of hepatitis B surface antigen (HBsAg) loss seen with PEG-IFNα alone in adults with virologically suppressed chronic hepatitis B virus (HBV) infection, according to late-breaking phase 2 data presented at The Liver Meeting 2026 in Denver, Colorado.¹

A separate cohort found that priming with BRII-179 and elebsiran allowed the PEG-IFNα course to be cut in half.² Brii Biosciences announced the findings on November 5, 2026, alongside results from its phase 2 ENRICH study. David Margolis, chief medical officer of Brii Bio, said in a statement that the findings "provide a stronger scientific foundation for the continued evaluation of BRII-179-based priming and enrichment strategies."³

Why Is HBsAg Loss the Target in Chronic Hepatitis B?

An estimated 254 million people were living with chronic HBV infection in 2022, according to the World Health Organization.⁴ Nucleos(t)ide analogues suppress HBV replication but rarely clear HBsAg, so most patients require long-term therapy. Functional cure, defined as sustained HBsAg loss with undetectable HBV DNA 24 weeks after stopping treatment, is the preferred endpoint for trials of finite therapies.⁵

On October 20, 2026, the US Food and Drug Administration approved bepirovirsen (Hibsago), the first antisense oligonucleotide for chronic HBV, for adults without cirrhosis whose HBV is suppressed and whose HBsAg is 3000 IU/mL or lower.⁶ That population closely overlaps the patients enrolled in ENHANCE.

How Did Triple Therapy Compare With Peginterferon Alone?

ENHANCE (NCT06650852) Part A-1 randomly assigned 147 participants without cirrhosis and with HBsAg levels greater than 100 and up to 3000 IU/mL 2:1 to triple therapy or 48 weeks of PEG-IFNα monotherapy. The primary endpoint was HBsAg loss at week 48.¹

At the end of treatment (EOT), HBsAg loss occurred in 25.5% (25/98) of participants receiving triple therapy vs 10.2% (5/49) receiving monotherapy (P = .03). Among those with baseline HBsAg above 1000 IU/mL, rates were 24.2% vs 0% (P = .04).¹

At 24 weeks after EOT, HBsAg loss was maintained in 17.3% of the triple therapy group vs 6.1% of the monotherapy group.¹,³ Durability was greater among participants with antibody to HBsAg (anti-HBs) of at least 100 IU/L at EOT (80% vs 20%). Safety was generally comparable between groups.¹

Can BRII-179 Priming Shorten Peginterferon Treatment?

In ENHANCE Part A2, 80 participants received 24 weeks of BRII-179 and elebsiran, followed by 24 weeks of elebsiran plus PEG-IFNα. At EOT, 22.5% achieved HBsAg loss, rising to 25.0% at 8 weeks after EOT. Participants with an anti-HBs response after priming had higher HBsAg loss rates than nonresponders (30.6% vs 15.9%).²

Interferon-associated adverse events, including decreased platelet count, pyrexia, and alopecia, were less frequent than with 48 weeks of PEG-IFNα in Part A-1. The investigators concluded that priming enabled a 50% reduction in PEG-IFNα exposure while maintaining comparable HBsAg loss rates.²

In the ENRICH study, 12 weeks of BRII-179 before elebsiran and PEG-IFNα produced HBsAg loss in 41.9% (62/148) of participants at EOT and 32.4% at 24 weeks after EOT, according to Brii. The company did not report a comparator arm.³

What Are the Limitations?

Only ENHANCE Part A-1 was randomized, so comparisons across cohorts should be interpreted cautiously. The abstracts do not report off-treatment HBV DNA, so the results cannot be classified as functional cure.¹,²,⁵ All study sites were in China, and the findings have not been published in a peer-reviewed journal.

References

1. Jia J, Gao Z, Lin J, et al. Elebsiran plus BRII-179 and peginterferon alfa achieve greater HBsAg loss and enhanced immune responses compared with peginterferon alfa alone in virologically suppressed chronic hepatitis B: results from the phase 2 ENHANCE Part A-1. Late-breaking abstract. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Jia J, Gao Z, Lin J, et al. Immune priming with BRII-179 and elebsiran enables shortened pegylated interferon alfa treatment while maintaining HBsAg loss in participants with chronic HBV infection: results from ENHANCE Part A2. Late-breaking abstract. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
3. Brii Biosciences. Brii Bio presents late-breaking data from its phase 2 ENRICH and ENHANCE studies at AASLD 2026 supporting BRII-179-based priming and enrichment strategy for HBV functional cure. News release. Published November 6, 2026. Accessed November 6, 2026. https://www.briibio.com/en/media/press-release/20261106/
4. World Health Organization. Global hepatitis report 2024: action for access in low- and middle-income countries. Published April 9, 2024. Accessed November 6, 2026. https://www.who.int/publications/i/item/9789240091672
5. Ghany MG, Buti M, Lampertico P, et al. Guidance on treatment endpoints and study design for clinical trials aiming to achieve cure in chronic hepatitis B and D: report from the 2022 AASLD-EASL HBV-HDV Treatment Endpoints Conference. Hepatology. 2023;78(5):1654-1673. doi:10.1097/HEP.0000000000000431
6. Campbell P. FDA approves bepirovirsen for chronic hepatitis B. HCPLive. Published October 20, 2026. Accessed November 6, 2026. https://www.hcplive.com/view/fda-approves-bepirovirsen-for-chronic-hepatitis-b