Vir Biotechnology Reports Positive Results for Tobevibart and Elebsiran in Hepatitis B Study

Vir Biotechnology, Inc., based in San Francisco, has unveiled promising findings from Part B of their MARCH Phase 2 clinical study. This study focuses on assessing the effectiveness of combining tobevibart and elebsiran, either with or without pegylated interferon alfa (PEG-IFNα), in treating chronic hepatitis B (CHB). The data from this study indicates a significant potential in achieving hepatitis B surface antigen (HBsAg) loss, particularly in participants with lower baseline levels of HBsAg (below 1000 IU/mL).

The clinical trial included 51 participants treated with tobevibart and elebsiran (doublet regimen), and 27 participants treated with the addition of PEG-IFNα (triplet regimen). Tobevibart was administered at 300 mg every four weeks, elebsiran at 200 mg every four weeks, and PEG-IFNα at 180 µg weekly. The primary goals of the study were to observe HBsAg seroclearance and record any treatment-emergent adverse events (TEAEs) by the end of the treatment. Secondary goals included the development of anti-HBs antibodies at the end of the treatment.

Results showed that the doublet and triplet regimens led to HBsAg loss in 39% and 46% of participants with baseline HBsAg levels under 1000 IU/mL, respectively. Overall, 16% of participants on the doublet regimen and 22% on the triplet regimen achieved HBsAg loss. Furthermore, 50% of those who achieved HBsAg loss in the doublet regimen also developed anti-HBs antibodies, whereas all participants in the triplet regimen who achieved HBsAg loss also developed these antibodies. Those who met the criteria for HBsAg seroclearance will discontinue treatment, and their functional cure will be assessed 24 weeks later.

Edward J. Gane, M.D., from the University of Auckland, commented on these findings, noting the potential of tobevibart and elebsiran to contribute to a functional cure for hepatitis B. The safety profile of the treatments was consistent with previous studies, showing mild to moderate TEAEs without new safety concerns.

Mark Eisner, M.D., M.P.H., Chief Medical Officer at Vir Biotechnology, expressed optimism about developing a functional cure for chronic hepatitis B. The MARCH study's data suggests that these treatments could clear HBsAg and stimulate the immune system to control the virus.

The detailed data will be presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® in San Diego on November 18. Participants who achieve HBsAg seroclearance by the end of treatment will discontinue treatment, with their functional cure being assessed 24 weeks post-treatment.

The MARCH Phase 2 study, a multi-center, open-label, non-randomized trial, aims to evaluate the safety, tolerability, and efficacy of these regimens. Primary endpoints include HBsAg seroclearance and TEAEs, with secondary endpoints involving anti-HBs antibody development. The study's design allows for assessment of sustained HBsAg loss 24 weeks after treatment discontinuation.

Tobevibart, a monoclonal antibody designed to inhibit the entry of hepatitis B and delta viruses into liver cells and reduce viral particles in the blood, is currently in clinical development. Elebsiran, designed to degrade hepatitis B virus RNA transcripts, shows potential for direct antiviral activity against both hepatitis B and delta viruses. It is also in clinical development.

Vir Biotechnology continues to focus on developing treatments for serious infectious diseases and cancer, with a portfolio that includes programs for chronic hepatitis delta and B infections.