Vir Biotechnology announced promising end-of-treatment results from Part B of its Phase 2 MARCH clinical trial, evaluating combinations of tobevibart and elebsiran, with or without pegylated interferon alfa (PEG-IFNα), in patients with chronic hepatitis B (CHB). The data, presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®, demonstrated notable rates of hepatitis B surface antigen (HBsAg) loss in participants with low baseline HBsAg levels (<1000 IU/mL). These findings suggest the potential for achieving a functional cure for CHB, a condition affecting an estimated 254 million people worldwide.
The MARCH trial is a Phase 2, multi-center, open-label, non-randomized study designed to assess the safety, tolerability, and efficacy of tobevibart and elebsiran, alone or combined with PEG-IFNα, in CHB patients. Participants received either tobevibart and elebsiran (doublet regimen) or tobevibart, elebsiran, and PEG-IFNα (triplet regimen). Tobevibart was administered at 300 mg every 4 weeks, elebsiran at 200 mg every 4 weeks, and PEG-IFNα at 180 μg weekly.
The primary endpoints included HBsAg seroclearance and treatment-emergent adverse events (TEAEs) at the end of treatment. Secondary endpoints included anti-HBs seroconversion at the end of treatment. The analysis included data from 51 participants in the doublet regimen arm and 27 participants in the triplet regimen arm.
Key Findings from the MARCH Trial
The doublet regimen resulted in HBsAg loss at the end of treatment in 39% (7/18) of participants with baseline HBsAg <1,000 IU/mL, while the triplet regimen achieved HBsAg loss in 46% (5/11) of participants in the same baseline HBsAg range. Overall, HBsAg loss was observed in 16% (8/51) of participants in the doublet arm and 22% (6/27) in the triplet arm, regardless of baseline HBsAg levels.
Notably, 50% (4/8) of participants who achieved HBsAg loss in the doublet regimen also achieved anti-HBs seroconversion. In the triplet regimen, all participants with HBsAg loss at the end of treatment achieved anti-HBs seroconversion (100%, 6/6).
Expert Commentary
Edward J. Gane, M.D., Professor of Medicine at the University of Auckland, commented on the results: "People living with chronic hepatitis B must settle for life-long treatments that don’t eliminate the risk of disease progression to liver cancer. 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."
Safety and Tolerability
The safety and tolerability profile of tobevibart and elebsiran remained consistent with previous studies. No new safety concerns were identified, and TEAEs were generally mild to moderate.
Future Directions
Participants who achieved HBsAg seroclearance at the end of treatment and met 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 next steps for clinical development.
Mark Eisner, M.D., M.P.H., Executive Vice President and Chief Medical Officer at Vir Biotechnology, stated, "At Vir Biotechnology our ambition is to develop a functional cure for chronic hepatitis B following a finite treatment regimen. 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."
