Vir Biotechnology has announced positive end-of-treatment data from Part B of its Phase 2 MARCH clinical study, evaluating combinations of tobevibart and elebsiran, with or without pegylated interferon alfa (PEG-IFNα), in participants with chronic hepatitis B (CHB). The study demonstrated encouraging rates of hepatitis B surface antigen (HBsAg) loss (seroclearance) in participants with low baseline HBsAg (<1000 IU/mL) in both combination regimens, supporting continued development towards a potential functional cure. The detailed findings were presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®.
Chronic hepatitis B, a long-lasting inflammatory liver disease caused by the hepatitis B virus (HBV), affects an estimated 254 million people worldwide and results in approximately 1.1 million deaths annually, according to the World Health Organization. CHB can lead to severe complications such as liver cirrhosis, liver failure, and liver cancer. While treatments exist, a definitive cure remains elusive.
Study Design and Results
The MARCH Phase 2 trial is a multi-center, open-label, non-randomized study evaluating the safety, tolerability, and efficacy of tobevibart (VIR-3434) and elebsiran (VIR-2218), alone or in combination with pegylated interferon alfa, in patients with chronic hepatitis B. Participants received either tobevibart and elebsiran alone (doublet regimen) or in combination with PEG-IFNα (triplet regimen). In the doublet regimen, 39% (7/18) of participants with baseline HBsAg <1,000 IU/mL achieved HBsAg loss at the end of treatment, while the triplet regimen resulted in HBsAg loss in 46% (5/11) of similar participants. Overall, HBsAg loss was observed in 16% (8/51) of participants in the doublet arm and 22% (6/27) in the triplet arm.
Notably, 50% (4/8) of participants who achieved HBsAg loss in the doublet regimen also achieved anti-HBs seroconversion (≥10 mIU/mL). 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 was consistent with prior studies, with no new safety concerns identified. Treatment-emergent adverse events (TEAEs) were generally mild or moderate.
Expert Commentary
Edward J. Gane, M.D., Professor of Medicine at the University of Auckland, New Zealand, stated, "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."
Future Directions
Participants who achieved HBsAg seroclearance at the end of treatment will discontinue treatment, with functional cure assessment occurring 24 weeks after treatment discontinuation. Vir Biotechnology anticipates releasing key functional cure data from the 24-week follow-up in Q2 2025.
Mark Eisner, M.D., M.P.H., Executive Vice President and Chief Medical Officer of Vir Biotechnology, commented, "The MARCH data suggests that tobevibart and elebsiran can clear HBsAg and re-ignite the immune system, producing antibodies to potentially keep the virus under control. We are encouraged by these results and eagerly anticipate the functional cure data in 2025, as it will be decisive for the next steps of clinical development."
