About one in three patients given BRII-179 as an immune primer before elebsiran and pegylated interferon held HBsAg loss at 24 weeks after treatment ended, results from the Phase 2b ENRICH study showed at AASLD 2026 this week. That 32.4% durability rate, drawn from 148 participants across two dosing cohorts, matched what Brii Bio first saw in ENSURE Cohort 4, where 29% achieved HBsAg loss at the same post-treatment checkpoint. Prospectively reproducing a signal from an earlier cohort is not routine, and the consistency tightens the case for BRII-179 as a priming agent rather than an incidental finding.
The harder problem, though, is patients with high baseline HBsAg, the group historically least likely to clear the virus. In ENRICH, among participants whose baseline HBsAg sat above 1,000 IU/mL and up to 3,000 IU/mL, roughly one in five (20.8%) maintained HBsAg loss at 24 weeks post-treatment. The parallel ENHANCE study tested how to sequence BRII-179 differently: Part A1 ran concurrent triple therapy with BRII-179, elebsiran (an investigational siRNA, not to be confused with Novartis’s inclisiran), and PEG-IFN, and hit 25.5% HBsAg loss at end of treatment versus 10.2% with PEG-IFN alone, a statistically significant gap. Among the high-baseline subgroup within Part A1, 24.2% on triple therapy cleared HBsAg at end of treatment compared with zero in the PEG-IFN monotherapy arm.
ENHANCE Part A2 added a mechanistic detail worth watching. Participants who mounted an anti-HBs response of at least 10 IU/L after a 24-week priming phase with BRII-179 and elebsiran achieved HBsAg loss at end of treatment at nearly twice the rate of non-responders, 30.6% versus 15.9%. That split suggests early immune response could function as a selection tool, identifying who is likely to benefit from the subsequent shortened PEG-IFN course before it starts. bepirovirsen (Hibsago) has been in late-stage development for chronic hepatitis B, with peginterferon alfa-2a carrying longstanding regulatory approval, so Brii Bio is not operating in an empty field. What it is trying to do is move durable functional cure rates in patients who do not respond well to existing regimens.
The anti-HBs response threshold at week 24 of priming is the number to follow as Brii Bio designs its next studies. If it holds as a predictive biomarker across a larger population, it could inform patient selection criteria for a Phase 3 program and reduce the exposure of likely non-responders to a prolonged PEG-IFN regimen.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
