Brii Bio presented promising new data from its ongoing Phase 2 ENSURE study at the 34th Annual Meeting of Asian Pacific Association for the Study of the Liver (APASL 2025), highlighting a novel approach to achieving functional cure for chronic hepatitis B virus (HBV) infection.
The data, presented as a late-breaking oral presentation, demonstrates that BRII-179, a recombinant protein-based HBV immunotherapeutic, may serve as a valuable predictive tool to identify patients more likely to respond to curative therapies.
BRII-179 Identifies Patients More Likely to Achieve HBsAg Clearance
The ENSURE study's Cohort 4 included participants who had previously received BRII-179 in combination with elebsiran (BRII-835) in a prior study. These patients subsequently received elebsiran plus pegylated interferon alpha (PEG-IFNα) treatment.
Among the 28 participants analyzed, those who had previously demonstrated an immune response to BRII-179 (defined as peak anti-HBs ≥10 IU/L) achieved a substantially higher rate of hepatitis B surface antigen (HBsAg) seroclearance compared to non-responders. At Week 24, 55.6% (10/18) of BRII-179 responders achieved HBsAg seroclearance, compared to only 10% (1/10) in non-responders.
"The positive Cohort 4 data from the ENSURE study opens new doors for HBV functional cure," said Dr. Grace Lai-Hung Wong, Professor of Gastroenterology and Hepatology at CUHK Medical Data Analytics Centre (MDAC) and Department of Medicine and Therapeutics in Hong Kong SAR, China. "Previous studies have suggested that BRII-179 may offer a unique opportunity to identify CHB patients who are able to elicit the necessary HBsAg antibody response. I believe these new findings provide clear evidence supporting such value proposition and further substantiate the role of BRII-179 in shaping future combination therapies."
Elebsiran Plus PEG-IFNα Shows Superior Results to PEG-IFNα Alone
Additional data from Cohorts 1-3 of the ENSURE study demonstrated that elebsiran, an investigational small interfering RNA (siRNA), in combination with PEG-IFNα achieved significantly higher end-of-treatment (EOT) HBsAg loss rates compared to PEG-IFNα monotherapy.
The rates of HBsAg seroclearance at EOT in the elebsiran 200 mg + PEG-IFNα and elebsiran 100 mg + PEG-IFNα cohorts were 26.3% (5/19) and 33.3% (6/18), respectively, notably higher compared to the PEG-IFNα alone cohort (5.6%) in participants with baseline HBsAg levels of 100-3,000 IU/mL.
Greater HBsAg reductions at EOT were also observed in the combination therapy groups, with mean reductions of -2.47 log10 IU/mL for elebsiran 200 mg and -3.01 log10 IU/mL for elebsiran 100 mg, compared to -1.02 log10 IU/mL in the PEG-IFNα monotherapy group.
Novel Enrichment Strategy for HBV Functional Cure
The findings support Brii Bio's novel enrichment strategy for developing a functional cure for chronic HBV. By using BRII-179 to identify patients who can mount an effective immune response, the company aims to enhance functional cure rates in the target population while reducing exposure to costly therapies for those with a lower probability of cure.
"We are encouraged that the Cohort 4 from the ENSURE study continue to support our enrichment strategy in developing a functional cure for chronic HBV in target populations," said David Margolis, MD, Chief Medical Officer of Brii Bio. "The results underscore the potential of BRII-179 in identifying patients who are more likely to respond to regimens aimed at functional cure, thereby enhancing functional cure rates in the target population while reducing exposure to costly therapies for those with a lower probability of cure."
Safety Profile and Ongoing Research
Both the elebsiran and PEG-IFNα combination therapy was generally safe and well-tolerated in participants with virally suppressed chronic HBV infection. Treatment with elebsiran + PEG-IFNα is ongoing for 48 weeks, with post-treatment follow-up continuing for 24 weeks after discontinuation of treatment.
As part of its comprehensive approach to developing a functional cure for HBV, Brii Bio and its partners are actively progressing multiple combination studies with their differentiated portfolio. This includes BRII-179 being evaluated in multiple combination studies with elebsiran, and elebsiran being evaluated in combination with PEG-IFNα and tobevibart (an investigational broadly neutralizing monoclonal antibody targeting HBV).
Significant Global Health Impact
Hepatitis B virus infection represents one of the world's most significant infectious disease threats, with more than 254 million people infected globally. Chronic HBV infection is the leading cause of liver disease, resulting in an estimated 820,000 deaths annually from related complications. The disease is particularly prevalent in China, where 87 million people are chronically infected.
BRII-179, which received Breakthrough Therapy Designation from China's Center for Drug Evaluation in November 2023, is a novel recombinant protein-based HBV immunotherapeutic candidate designed to induce enhanced and broad B-cell and T-cell immunity by expressing the Pre-S1, Pre-S2, and S HBV surface antigens.
Elebsiran, licensed from Vir Biotechnology for the Greater China territory, is an investigational subcutaneously administered HBV-targeting siRNA designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen, with potential direct antiviral activity against both HBV and HDV.
Key data readouts from these ongoing studies will be shared in the coming months at scientific conferences throughout 2025, potentially bringing the field closer to a functional cure for this challenging global health issue.
