Brii Biosciences has reported topline end-of-treatment data from its ongoing Phase 2b ENRICH and ENHANCE studies evaluating combination regimens for chronic hepatitis B virus infection.
The studies are assessing BRII-179 in combination with elebsiran and pegylated interferon alfa. ENRICH evaluates BRII-179 as a priming therapy before elebsiran and PEG-IFNα treatment, while ENHANCE evaluates concurrent triple combination approaches.
This is relevant because chronic hepatitis B remains a major global health burden, particularly in Asia. Current antiviral therapies can suppress viral replication, but functional cure remains difficult to achieve. HBsAg loss is an important endpoint because it is associated with improved long-term outcomes and is widely used to evaluate potential functional cure strategies.
In ENRICH, BRII-179 pre-treatment followed by elebsiran and PEG-IFNα produced end-of-treatment HBsAg loss rates of 42.9 per cent and 40.0 per cent across two dosing schedules. These results were consistent with a 41.9 per cent HBsAg loss rate observed in ENSURE Cohort 4 among patients with prior BRII-179 treatment.
The results support the hypothesis that BRII-179 may prime immune responses before subsequent antiviral and immune-modulating therapy. This is important because functional cure strategies for chronic hepatitis B may require both viral antigen reduction and immune restoration.
The ENHANCE Part A-1 concurrent triple combination did not improve HBsAg loss rates compared with earlier ENSURE Cohorts 2 and 3. The observed HBsAg loss rate was 25.5 per cent, although this was higher than the PEG-IFNα control arm rate of 10.2 per cent.
ENHANCE Part A-2, which evaluated a sequential approach intended to shorten PEG-IFNα treatment duration, achieved an end-of-treatment HBsAg loss rate of 22.5 per cent. Brii Bio noted that this suggests a full course of PEG-IFNα may be needed for optimal curative outcome.
The data are clinically useful because they help clarify regimen selection. Not every combination strategy produced the same effect, and the results suggest timing and sequencing may be important when combining immune-modulating and antiviral approaches.
No new safety concerns were identified in either study. However, HBsAg loss at end of treatment must be confirmed during off-treatment follow-up to assess rebound and durability of functional cure.
Brii Bio said advancement of ENRICH into Phase 3 remains subject to the outcome of arbitration with Vir Biotechnology related to elebsiran manufacturing technology transfer. This introduces a development and execution risk even though the ENRICH regimen showed stronger end-of-treatment signals.
The company has engaged with China’s Center for Drug Evaluation and reached preliminary alignment on a potential registrational study. This gives the programme regulatory relevance in a region where chronic hepatitis B remains a significant public health priority.
The development reflects the complexity of chronic hepatitis B cure research. Future success will likely depend on selecting the right combination, sequence and patient population rather than relying on a single antiviral mechanism.
