Vir Biotechnology announced positive end-of-treatment results from Part B of its MARCH Phase 2 clinical study. This study is evaluating combinations of tobevibart and elebsiran, with and without pegylated interferon alfa (PEG-IFNα), for chronic hepatitis B. The study showed promising hepatitis B surface antigen (HBsAg) loss (seroclearance) rates in participants with low baseline HBsAg (<1000 IU/mL) using both combination regimens. These positive efficacy and safety results support further development to explore the potential for a functional cure. Detailed findings will be presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® in San Diego, CA on November 18th. Vir Biotechnology will also host an investor conference call on November 19th. Chronic hepatitis B (CHB) is a persistent, inflammatory liver disease caused by the hepatitis B virus (HBV). This global health concern affects an estimated 254 million people, with approximately 1.1 million deaths annually attributed to the disease and its complications, which can include cirrhosis, liver failure, and liver cancer. While CHB treatments exist, there is currently no cure.
The MARCH trial participants received either tobevibart and elebsiran (doublet regimen) or these two medications combined with PEG-IFNα (triplet regimen). The analysis included data from 51 participants in the doublet arm and 27 in the triplet arm. Tobevibart was administered every four weeks at 300 mg, elebsiran at 200 mg every four weeks, and PEG-IFNα weekly at 180 µg. Primary endpoints were HBsAg seroclearance (HBsAg below the lower limit of quantification) and treatment-emergent adverse events (TEAEs) at the end of treatment. Anti-HBs seroconversion (development of anti-HBs≥10 mIU/mL) at treatment end was a secondary endpoint. The results showed HBsAg loss in 39% (7/18) of participants with baseline HBsAg<1,000 IU/mL in the doublet arm and 46% (5/11) in the triplet arm. Overall HBsAg loss rates were 16% (8/51) for the doublet regimen and 22% (6/27) for the triplet regimen across all baseline HBsAg levels. In the doublet regimen group, 50% (4/8) of participants who achieved HBsAg loss also achieved anti-HBs seroconversion. All participants achieving HBsAg loss in the triplet group also achieved anti-HBs seroconversion (100%, 6/6).
Eligible participants who achieved HBsAg seroclearance at the end of treatment discontinued treatment. Functional cure assessment will take place 24 weeks post-treatment discontinuation. The combined tobevibart and elebsiran treatment showed a consistent safety and tolerability profile compared to previous studies, without any new safety concerns arising. Observed TEAEs were generally mild to moderate. Vir Biotechnology aims to develop a functional cure for chronic hepatitis B through a finite treatment regimen. The MARCH data suggests that tobevibart and elebsiran may be able to clear HBsAg and stimulate the immune system to produce antibodies, potentially controlling the virus. The functional cure data expected in 2025 will be crucial for determining the next steps in clinical development. The study results will be presented in an oral presentation titled “Tobevibart (VIR-3434) and elebsiran (VIR-2218) with or without pegylated interferon alfa-2a for the treatment of chronic HBV infection: end of treatment results after 48 weeks of therapy (MARCH study)” during a late-breaking parallel session at AASLD The Liver Meeting® on November 18th.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
