Clinical trial results from two Phase 2b studies have been released.
The ongoing Phase 2b ENRICH and ENHANCE studies have concluded their treatment phase, with top-line results now available.
These studies are designed to evaluate sequential and concurrent combination regimens of BRII-179 with elebsiran and pegylated interferon alpha (PEG-IFNα) for the treatment of chronic hepatitis B virus (HBV) infection.
The ENRICH and ENHANCE trials are two Phase 2b studies intended to further clarify the role of BRII-179 in chronic HBV therapy and to identify the optimal combination regimen for subsequent development.
The ENRICH study assessed the effect of administering BRII-179 as an immunopriming treatment prior to therapy with elebsiran and PEG-IFNα.
The ENHANCE study evaluated a triple concurrent administration regimen of BRII-179, elebsiran, and PEG-IFNα, aiming to improve functional cure rates.
At the end of treatment, the ENRICH study showed that in the regimen where BRII-179 was administered first, followed by a combination of elebsiran and PEG-IFNα, hepatitis B surface antigen (HBsAg) clearance rates of 42.9% (42/98) and 40.0% (20/50) were achieved under two different BRII-179 dosing schedules, corresponding to dosing once every three weeks for a total of five doses and once every two weeks for a total of seven doses, respectively.
This result aligns with the 41.9% (13/31) HBsAg clearance rate observed in previously BRII-179-treated patients from ENSURE Cohort 4, supporting the immunopriming effect of BRII-179.
The company has communicated with the Center for Drug Evaluation of the National Medical Products Administration regarding a potential registrational study and has reached a preliminary consensus.
At the end of treatment, the triple concurrent regimen evaluated in the ENHANCE (Part A-1) study did not show an improvement in HBsAg clearance rates compared to ENSURE Cohorts 2 and 3, where the end-of-treatment HBsAg clearance rate was 29.7% (11/37). In this study, the rate was 25.5% (25/98).
However, a higher HBsAg clearance rate was observed with this triple regimen compared to the PEG-IFNα control group, which had a rate of 10.2% (5/49).
Subgroup analysis from the ENRICH study suggests that the treatment regimen may have a differential performance in patients with higher baseline HBsAg levels (1,000-3,000 IU/mL), consistent with previous observations from ENSURE Cohort 4.
This indicates that BRII-179 may induce a favorable immune response in this more difficult-to-treat population, regardless of baseline HBsAg levels.
Part A-2 of the ENHANCE study also evaluated a sequential treatment regimen designed to potentially shorten the PEG-IFNα course, involving BRII-179 combined with elebsiran for the first 24 weeks, followed by combined treatment with elebsiran and PEG-IFNα for the subsequent 24 weeks.
At the end of treatment, this regimen achieved an HBsAg clearance rate of 22.5% (18/80), suggesting that a full course of PEG-IFNα treatment remains crucial for achieving the best curative outcome.
HBsAg clearance is an important endpoint for assessing functional cure regimens, but its durability and the potential for rebound need to be confirmed through post-treatment follow-up.
No new safety signals were identified in either study.
The company plans to present detailed data, including further efficacy, safety, subgroup analyses, and follow-up results, at an academic conference in the second half of 2026.
Dr. David Margolis, the company's Chief Medical Officer, stated: "These initial end-of-treatment data provide an important basis for evaluating the relative performance of the ENRICH and ENHANCE study designs. While longer-term follow-up is still needed to assess the durability of HBsAg clearance, the currently observed data are highly consistent with end-of-treatment and post-treatment results from multiple previous studies, supporting the ENRICH design as the preferred option for a registrational study. We look forward to sharing more complete data later this year."
As previously disclosed, due to an ongoing arbitration with Vir Biotechnology, Inc., where the outcome, timing, and potential for a settlement remain uncertain, the company considers the future of the elebsiran project to be uncertain.
Specifically, unless and until claims in the arbitration are satisfactorily resolved, the company will be unable to invest in any Phase 3 clinical studies for hepatitis B combination regimens containing elebsiran.
The company will continue to evaluate relevant developments, assess their impact on the prospects for advancing the elebsiran project, and will provide updates to its shareholders and the public as required by applicable regulations.
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