The hepatitis B virus (HBV) vaccine is up to 90 percent effective at preventing HBV when given within 24 hours after birth. But for the hundreds of millions of people around the world who have already acquired the viral infection that attacks their liver, there is no cure. Current standard treatments consist of daily, lifelong antiviral therapies where the virus still hides within liver tissue.
Therapies that lead to a functional cure for HBV are in the works, with Brii Biosciences recently announcing results of their Phase 2b ENRICH and ENHANCE trials. The trials tested the immunotherapy, BRII-179 in combination with the siRNA drug elebsiran discovered by Alnylam Pharmaceuticals and licensed by Vir Biotechnology, and the FDA-approved antiviral PEG-IFN alpha (pegylated interferon-alpha).
The new results suggest that a priming strategy whereby BRII-179 is introduced before treatment with elebsiran and PEG-IFN alpha could result in a new functional cure approach for patients.
“These initial [end-of-treatment] data provide important insights into the relative performance of the ENRICH and ENHANCE study designs,” said David Margolis, Chief Medical Officer of Brii Biosciences, in the press release.
An uncertain future
While the company noted that they will share the full dataset at a scientific conference later this year, they noted in the recent report that the priming strategy studied in the ENRICH trial achieved hepatitis B surface antigen (HBsAg) loss rates of 42.9 percent with five doses every three weeks and 40 percent with seven doses every two weeks. The addition of the siRNA drug elebsiran specifically produced higher functional cure rates compared to PEG-IFN alpha alone (which achieved a 10.2 percent functional cure rate).
The ENHANCE study, on the other hand, showed that concurrent administration of the three medications was not as effective, with a HBsAg loss rate of 25.5 percent.
“While longer-term follow-up is needed to assess durability of the HBsAg loss, the data observed to date, together with EOT and post-EOT findings from multiple prior studies, are very consistent, suggesting that the ENRICH study design is preferred for a registrational study,” said Margolis in the statement.
Despite the promising new priming approach with BRII-179, the company emphasized in the statement that future Phase 3 trials remain in limbo at this time due to ongoing arbitration with Vir Biotechnology. “In particular, the Company cannot invest in a Phase 3 clinical study of any elebsiran-containing combination therapy for HBV unless and until the claims in the Arbitration are satisfactorily resolved. The Company will continue to evaluate such developments and assess their impact on the continued viability of the elebsiran program, and update its shareholders and the public as and when appropriate in accordance with relevant requirements,” stated the company in the news release.
The dispute centers around the manufacturing of elebsiran after Brii Biosciences filed a claim on April 16th, 2026 regarding a breach in their 2018 Collaboration, Option, and License Agreement and a letter agreement from 2024.
Hope for another HPV functional cure around the corner
With the future of Brii Biosciences’ combination treatment up in the air, patients with HBV have hope that another functional cure therapy may arrive sooner.
On August 24th, GSK announced that Japan’s Ministry of Health, Labour, and Welfare approved bepirovirsen, their antisense oligonucleotide (ASO) — representing the first time a functional cure for HBV has been approved.
Though no direct head-to-head comparisons can be made between GSK and Brii Biosciences’ functional cure treatments at present because of major differences in study designs and patient populations — and end-of-treatment results do not yet meet the true definition of a functional cure — it’s possible that more long-term data could show an edge for Brii Biosciences. Their press release noted that based on a subgroup analysis from the ENRICH study, patients with higher baseline HBsAg levels (1,000-3,000 IU/mL) may still have beneficial immune responses, while GSK’s bepirovirsen achieved a lower functional cure rate in patients up to 3,000 IU/mL.
The FDA accepted GSK’s New Drug Application for Priority Review, with a decision expected in late October. Reviews are also underway in Europe, Canada, and China.
If approved, it could open up the first functional cure to patients all over the world and allow them a treatment option that can be completed in just six months instead of lifelong.
