Brii Biosciences Limited, dual-head-quartered in Beijing, China, and North Carolina, reported end-of-treatment data from two Phase IIb studies that clarify the optimal combination strategy for BRII-179 in chronic HBV. However, a legal dispute with Vir Biotechnology (Nasdaq: VIR) over the manufacturing of elebsiran, the siRNA partner drug, now stands between these results and any Phase III program.
The ENRICH study, which tested BRII-179 as a priming immunotherapy administered before elebsiran and Roche's Pegasys (peginterferon alfa-2a), demonstrated hepatitis B surface antigen (HBsAg) loss rates of approximately 42–43% at end of treatment across two dosing schedules. Those figures are consistent with the 41.9% HBsAg loss observed in ENSURE Cohort 4, the earlier study that established BRII-179's immune-priming rationale. The replication across independent cohorts strengthens the mechanistic case: BRII-179 is a recombinant HBV surface antigen immunotherapeutic designed to restore HBV-specific T- and B-cell responses, while elebsiran suppresses all HBV RNA transcripts via RNA interference, reducing antigen load and immune exhaustion ahead of peginterferon alfa-2a treatment.
The ENHANCE study told a different story. The concurrent triple combination arm — BRII-179, elebsiran, and peginterferon alfa-2a given simultaneously — produced an HBsAg loss rate of 25.5%, falling short of the 29.7% benchmark from ENSURE Cohorts 2 and 3. A sequential sub-arm designed to shorten peginterferon alfa-2a exposure achieved only 22.5% HBsAg loss, suggesting that a full course of the interferon is necessary for optimal outcomes. Together, the two studies point toward sequential immune priming — not concurrent administration — as the preferred design for a registrational program.
Cross-trial comparisons are limited by differences in patient populations and study designs, but the ENRICH rates meaningfully exceed the roughly 10% HBsAg loss typically reported with peginterferon alfa-2a monotherapy in virally suppressed patients, and approach the functional cure rates seen in ENSURE final results presented at EASL 2026. No new safety signals were identified in either study.
The arbitration problem
The data are arguably the strongest Brii Bio has generated in its HBV program, and the company has reached preliminary alignment with China's National Medical Products Administration on a potential registrational study design. Legal issues mean that trial is currently in limbo. Brii licensed elebsiran from Vir Biotechnology for the Greater China territory in 2020, and an arbitration over the manufacturing technology transfer initiated in April 2026 means the company cannot commit capital to a Phase III study until the dispute is resolved. The outcome and timing of that arbitration remain unknown.
This creates a strategic asymmetry. The ENRICH data validate the sequential BRII-179 priming approach with sufficient consistency to justify Phase III investment, but the program is effectively in a holding pattern. Vir, meanwhile, has pivoted elebsiran's primary development focus toward chronic hepatitis delta, where the ECLIPSE Phase III registrational program is underway with tobevibart. Vir's Phase II MARCH data in chronic HBV, presented at EASL 2025, showed functional cure in only 4%–10% of all participants with tobevibart and elebsiran combinations with or without, rising to 11% and 15% in the lower-baseline-HBsAg subgroup, suggesting that the antibody-siRNA approach may face limitations in CHB without an additional immune-priming component.
The broader competitive context for HBV functional cure adds urgency. AusperBio Therapeutics is advancing AHB-137, an antisense oligonucleotide, through Phase III in China after reporting 48-week Phase II data showing sustained antiviral responses. GSK's bepirovirsen had an NDA under Priority Review with a PDUFA date in October 2026. The functional cure space is moving, and Brii Bio's window to establish the BRII-179 sequential regimen as a registrational-ready strategy is contingent on a legal resolution that remains outside its control. Full efficacy and durability data, including off-treatment follow-up to confirm sustained HBsAg loss, are expected at a scientific conference in the second half of 2026.
This article was generated with AI assistance and reviewed and edited by the AllSci editorial team
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