During the EASL (European Association for the Study of the Liver) Congress 2024, new findings were unveiled from two Phase 2 investigations assessing the efficacy of BRII-179, a novel recombinant protein-based HBV immunotherapeutic candidate. It was explored both as a combined therapy with BRII-835 (elebsiran) and as an additional treatment to pegylated interferon-alpha (PEG-IFNα) for chronic hepatitis B virus (HBV) infection.1
Main Takeaways
- Phase 2 trials highlight BRII-179's efficacy in combination therapy, showing improvements in end-of-treatment HBsAg loss rate and NRTI discontinuation rate, indicating the potential for sustained HBsAg loss post NRTI discontinuation.
- The safety and tolerability profile of the combination treatment of BRII-179 and PEG-IFNα proved favorable, with adverse events comparable to those previously reported for both components, supporting further clinical investigation.
- Data from Phase 2 trials suggest BRII-179's role in inducing significant HBV-specific B and T cell responses, correlated with antiviral effects in participants with chronic HBV infection, potentially impacting sustained control of viral infection.
Late-Breaker Poster
Phase 2 study aimed at assessing the efficacy of BRII-179 as an additional treatment to PEG-IFNα and nucleos(t)ide reverse transcriptase inhibitors (NRTI) therapy in managing HBV.2
The investigational combination treatment of BRII-179 and PEG-IFNα proved generally safe and well-tolerated, with adverse events like those previously reported for PEG-IFNα and BRII-179. The addition of BRII-179 elicited functional immune responses, leading to improvements in end-of-treatment HBsAg loss rate and NRTI discontinuation rate, with potential benefits for sustained HBsAg loss post NRTI discontinuation. These findings align with results from another Brii-sponsored study, indicating that BRII-179-induced immune responses, characterized by high HBsAb levels, strong neutralizing activity, and specific T-cell responses, contribute to HBsAg reduction.2
The combination treatment of BRII-179 and PEG-IFNα was generally safe and well-tolerated, with most treatment-emergent adverse events (TEAEs) being of Grade 1 or 2 severity, consistent with previous reports for both PEG-IFNα and BRII-179. The safety profile of the BRII-179 + PEG-IFNa combination group, except for injection site reactions, resembled that of the Placebo + PEG-IFNα group. Most TEAEs occurred during the dosing period, with no new risks identified during the follow-up, or non-dosing monitoring period (NDMP).2
All in all, the favorable balance of benefits and risks supports further clinical investigation of BRII-179 in combination with PEG-IFNα as essential components for the treatment of chronic HBV infection, to achieve a functional cure for chronic HBV.2
Oral presentation
Phase 2 clinical trial data showcased the efficacy of combining BRII-179, a therapeutic vaccine, with BRII-835 (elebsiran) in eliciting significant HBV-specific B and T cell responses. These responses were found to correlate with antiviral effects in a subset of participants with chronic HBV infection. An exploratory translational study investigated the relationship between treatment-induced immune responses and antiviral effects.3
In participants receiving combination therapy of siRNA BRII-835 and Tx Vax BRII-179, a Pre-S1-specific T cell response targeting a region adjacent to NTCP was found to be linked with significant reductions in HBsAg levels. Specifically, those displaying high reductions in HBsAg showed the presence of ex vivo Pre-S1-specific Th1-type cytokines (such as IL-2), whereas Th2-type responses did not correlate with HBsAg reduction. Additionally, BRII-179 triggered strong anti-HBV neutralizing activity in participants with reductions in HBsAg levels, accompanied by the induction of HBsAb.3
“This study shows for the first time direct evidence that immune responses induced by an HBV therapeutic vaccine is associated with HBsAg reduction and viral control in some participants with chronic HBV infection,” said Antonio Bertoletti, MD, Professor, Emerging Infectious Diseases Program at Duke-NUS Medical School. “The antiviral activity appears to be linked with a boosting of anti-HBs antibodies and Pre-S1-specific T cell responses induced by BRII-179, supporting that BRII-179 can break immune tolerance and have an impact on sustained control of the viral infection.”3
These findings suggest a promising role for BRII-179 in inducing targeted immune responses and neutralizing activity against HBV infection.
References
Brii Biosciences. Brii Bio Presents New Data from Its Ongoing Phase 2 Chronic Hepatitis B Trials at EASL™ Congress 2024. Published June 7, 2024. Accessed June 11, 2024. https://www.briibio.com/en/media/press-release/20240607/
Late-breaker poster. Zhu Q. BRII-179 induced functional immune response, demonstrating potential to improve chronic hepatitis B functional cure. European Association for the Study of the Liver (EASL) June 5-8, 2024, Milan, Italy.
Oral Abstract. Ji Y, Bert N, Lee A, et. al. Therapeutic vaccine (BRII-179) induced immune response associated with HBsAg reduction in a subset of participants with chronic hepatitis B. European Association for the Study of the Liver (EASL) June 5-8, 2024, Milan, Italy.
