Vir Biotechnology, Inc. (VIR) recently announced end-of-treatment data from Part B of its MARCH Phase 2 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, particularly in participants with low baseline HBsAg levels. These findings suggest a potential path toward functional cures for CHB, a significant global health challenge.
The MARCH Phase 2 trial investigated the efficacy of tobevibart and elebsiran, administered alone (doublet regimen) or in combination with PEG-IFNα (triplet regimen). The primary focus was on achieving HBsAg loss (seroclearance), a key indicator of viral control and potential functional cure.
Promising HBsAg Loss Rates
The study revealed that both the doublet and triplet regimens led to notable HBsAg loss in participants with low baseline HBsAg (<1000 IU/mL). Specifically, the doublet regimen resulted in HBsAg loss at the end of treatment in 39% (7/18) of participants, while the triplet regimen achieved HBsAg loss in 46% (5/11) of participants within this subgroup. When considering all participants, regardless of baseline HBsAg levels, the doublet regimen resulted in HBsAg loss in 16% (8/51) and the triplet regimen in 22% (6/27).
Anti-HBs Seroconversion
In addition to HBsAg loss, the study assessed anti-HBs seroconversion, another marker of immune control. The doublet regimen led to 50% (4/8) of participants achieving both HBsAg loss and anti-HBs seroconversion. Notably, all participants who experienced HBsAg loss in the triplet regimen also achieved anti-HBs seroconversion (100%, 6/6).
Next Steps and Functional Cure Assessment
Participants who achieved HBsAg seroclearance at the end of treatment and meet eligibility criteria will discontinue treatment. A functional cure assessment will be conducted 24 weeks after treatment discontinuation to evaluate the durability of the response.
Management Commentary
Mark Eisner, Executive Vice President and Chief Medical Officer at Vir Biotechnology, expressed optimism about the results, stating, “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.”
Chronic Hepatitis B: A Global Health Burden
Chronic hepatitis B (CHB) is a persistent inflammatory liver disease caused by the hepatitis B virus (HBV). The World Health Organization estimates that 254 million people live with CHB, and approximately 1.1 million deaths are associated with the disease annually. The development of effective therapies that can lead to functional cures is crucial to addressing this significant global health burden.
