Vir Biotechnology, Inc. has 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-IFNa), in participants with chronic hepatitis B (CHB). The results indicate promising rates of hepatitis B surface antigen (HBsAg) loss (seroclearance), especially in participants with low baseline HBsAg levels (<1000 IU/mL) in both combination regimens.
The study's findings support continued development of the combination therapy to evaluate its potential to achieve a functional cure for CHB, a long-lasting inflammatory liver disease caused by the hepatitis B virus (HBV). The World Health Organization estimates that 254 million people live with CHB, with approximately 1.1 million deaths annually associated with the disease. Complications from CHB include liver cirrhosis, liver failure, and liver cancer. While treatments exist, a definitive cure remains elusive.
Study Design and Results
The MARCH Phase 2 trial involved participants receiving tobevibart and elebsiran alone (doublet regimen) or in combination with PEG-IFNa (triplet regimen). The analysis included data from 51 participants in the doublet regimen arm and 27 participants in the triplet regimen arm at the end of treatment. Tobevibart was administered at 300 mg every 4 weeks, elebsiran at 200 mg every 4 weeks, and PEG-IFNa at 180 μg weekly.
The primary endpoints of the study included HBsAg seroclearance (defined as HBsAg below the lower limit of quantification) and treatment-emergent adverse events (TEAEs) at the end of treatment. Secondary endpoints included anti-HBs seroconversion (defined as development of anti-HBs ≥10 mIU/mL) at the end of treatment.
Results showed that the doublet and triplet regimens resulted in HBsAg loss at the end of treatment in 39% (7/18) and 46% (5/11) of participants with baseline HBsAg <1,000 IU/mL, respectively. Overall, the proportion of participants with varying baseline HBsAg levels who achieved HBsAg loss at the end of treatment was 16% (8/51) for the doublet and 22% (6/27) for the triplet regimen.
Anti-HBs Seroconversion and Safety
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). Participants with HBsAg seroclearance at the end of treatment who meet eligibility criteria will discontinue treatment, with functional cure assessment occurring 24 weeks after treatment discontinuation.
The safety and tolerability profile of tobevibart and elebsiran was consistent with prior studies, and no new safety concerns were identified. TEAEs were generally mild or moderate.
