Vir Biotechnology announced positive end-of-treatment data from Part B of the MARCH Phase 2 clinical study, evaluating combinations of tobevibart and elebsiran, with or without pegylated interferon alfa (PEG-IFNα), in participants with chronic hepatitis B. The results, presented at The Liver Meeting® during AASLD, demonstrated promising rates of hepatitis B surface antigen (HBsAg) loss in participants with low baseline HBsAg (<1000 IU/mL) in both combination regimens.
Promising HBsAg Loss with Combination Therapies
The MARCH trial investigated the efficacy of tobevibart and elebsiran, with or without PEG-IFNα, in achieving HBsAg loss, a key indicator of functional cure in chronic hepatitis B. The study included 51 participants in the doublet regimen (tobevibart and elebsiran) arm and 27 participants in the triplet regimen arm (tobevibart, elebsiran, and PEG-IFNα). Tobevibart was administered at 300 mg every 4 weeks, elebsiran at 200 mg every 4 weeks, and PEG-IFNα at 180 μg weekly.
The data revealed that in participants with baseline HBsAg <1,000 IU/mL, 39% (7/18) in the doublet regimen and 46% (5/11) in the triplet regimen achieved HBsAg loss at the end of treatment. Overall, HBsAg loss was observed in 16% (8/51) of participants in the doublet arm and 22% (6/27) in the triplet arm.
Anti-HBs Seroconversion
In addition to HBsAg loss, the study assessed anti-HBs seroconversion, which indicates the development of antibodies against the hepatitis B virus. Among participants who achieved HBsAg loss in the doublet regimen, 50% (4/8) also achieved anti-HBs seroconversion. Notably, all participants with HBsAg loss in the triplet regimen achieved anti-HBs seroconversion (100%, 6/6).
Safety and Tolerability
The safety and tolerability profile of tobevibart and elebsiran remained consistent with prior studies, with no new safety concerns identified. Treatment-emergent adverse events (TEAEs) were generally mild to moderate.
Expert Commentary
Edward J. Gane, M.D., Professor of Medicine at the University of Auckland, commented on the results, stating, "These latest data at end of treatment are encouraging as they suggest that tobevibart in combination with elebsiran could be key components for a hepatitis B functional cure. I look forward to the further results from this study anticipated next year."
Next Steps
Participants who achieved HBsAg seroclearance at the end of treatment and meet eligibility criteria will discontinue treatment. The assessment of functional cure, defined as sustained off-treatment HBsAg loss, will occur 24 weeks after treatment discontinuation. These data, expected in Q2 2025, will be crucial in determining the future clinical development path for tobevibart and elebsiran.
About Tobevibart and Elebsiran
Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen, designed to inhibit viral entry and reduce viral particle levels. Elebsiran is an investigational siRNA designed to degrade hepatitis B virus RNA transcripts and limit HBsAg production. Both are administered subcutaneously and are in clinical development for chronic hepatitis B and hepatitis delta.
