Brii Bio reported Phase 2b end-of-treatment data showing sequential BRII-179 treatment achieved up to 42.9% HBsAg loss in chronic hepatitis B, supporting Phase 3 development pending resolution of the elebsiran arbitration.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
Brii Biosciences has reported end-of-treatment (EOT) data from its ongoing Phase 2b ENRICH (NCT06491563) and ENHANCE studies (NCT06650852) evaluating combination strategies incorporating BRII-179, elebsiran, and pegylated interferon-alpha (PEG-IFNα) for chronic hepatitis B virus (HBV) infection.
The results indicate that administering BRII-179 before antiviral therapy produced higher hepatitis B surface antigen (HBsAg) loss rates than concurrent triple therapy, supporting the sequential regimen as the preferred strategy for future registrational development.
The company also confirmed that advancement of the ENRICH program into Phase 3 remains dependent on the outcome of its ongoing arbitration with Vir Biotechnology regarding the technology transfer for elebsiran manufacturing.
BRII-179 Supports Immune Priming for Functional Cure
Chronic hepatitis B affects more than 254 million people worldwide and remains a leading cause of cirrhosis, liver failure, and hepatocellular carcinoma. Although current antiviral therapies effectively suppress viral replication, they rarely achieve a functional cure, defined by sustained HBsAg loss after treatment discontinuation.
BRII-179 is a recombinant protein-based immunotherapy targeting the HBV Pre-S1, Pre-S2, and S surface antigens to stimulate broad B-cell and T-cell immune responses. Elebsiran is an investigational small interfering RNA (siRNA) that suppresses HBV RNA transcripts and reduces HBsAg production. Combining antiviral suppression with immune restoration represents a promising strategy for achieving durable functional cure.
ENRICH Demonstrated Higher HBsAg Loss Rates
The Phase 2b ENRICH study evaluated sequential treatment in which patients received BRII-179 before initiating elebsiran and PEG-IFNα.
At end of treatment, HBsAg loss reached:
- 42.9% (42/98) among patients receiving five BRII-179 doses every three weeks.
- 40.0% (20/50) among patients receiving seven doses every two weeks.
These findings closely matched the 41.9% (13/31) HBsAg loss rate previously reported in ENSURE Cohort 4, reinforcing the proposed immune-priming effect of BRII-179 before antiviral combination therapy.
Subgroup analyses also suggested benefit in patients with baseline HBsAg levels between 1,000 and 3,000 IU/mL, a population generally considered more difficult to treat.
Based on these findings, Brii Bio has held preliminary discussions with China’s Center for Drug Evaluation (CDE) regarding a potential registrational study.
Concurrent Triple Therapy Failed to Improve Outcomes
The ENHANCE Part A-1 study investigated concurrent administration of BRII-179, elebsiran, and PEG-IFNα.
The regimen achieved an HBsAg loss rate of 25.5% (25/98), compared with 29.7% (11/37) previously observed across ENSURE Cohorts 2 and 3 (NCT05970289), indicating no improvement with simultaneous treatment. However, efficacy remained higher than the PEG-IFNα control arm, which achieved HBsAg loss in 10.2% (5/49) of patients.
ENHANCE Part A-2 evaluated another sequential strategy intended to shorten PEG-IFNα exposure. Patients received BRII-179 plus elebsiran for 24 weeks followed by 24 weeks of elebsiran with PEG-IFNα. This regimen produced an HBsAg loss rate of 22.5% (18/80), suggesting that a full course of PEG-IFNα remains necessary to maximize functional cure rates.
No new safety concerns emerged in either Phase 2b study.
Findings Guide Future Development Strategy
Chief Medical Officer Dr. David Margolis said the EOT findings, together with results from earlier studies, consistently favor the ENRICH sequential treatment strategy for future registrational development. He noted that longer off-treatment follow-up will determine whether HBsAg loss remains durable, a critical requirement for establishing functional cure.
Brii Bio plans to present comprehensive efficacy, safety, subgroup, and post-treatment follow-up data at a scientific conference during the second half of 2026.
Despite the encouraging clinical findings, the future of the elebsiran program remains uncertain. The company reiterated that it cannot initiate a Phase 3 trial involving elebsiran until its arbitration with Vir Biotechnology is resolved. The outcome of those proceedings will determine the timeline for advancing the ENRICH regimen toward potential regulatory registration.
What This Means for Patients
The results suggest that giving BRII-179 before elebsiran and PEG-IFNα may improve the chances of achieving a functional cure for chronic hepatitis B compared with starting all three treatments together.
However, these are end-of-treatment results, and longer follow-up is needed to confirm whether patients maintain HBsAg loss after therapy ends. Phase 3 development is also on hold until Brii Bio resolves its ongoing legal dispute with Vir Biotechnology. If confirmed in future studies, this treatment approach could offer patients a better chance of long-term control of hepatitis B without lifelong therapy.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.