Vir Biotechnology Reports Initial 24-Week Post-Treatment Data for Tobevibart and Elebsiran in Chronic Hepatitis B from MARCH Study

Vir Biotechnology, Inc. has released new findings from the MARCH Phase 2 clinical study concerning treatments for chronic hepatitis B (CHB). These results were shared during the European Association for the Study of the Liver congress held in Amsterdam, and they offer promising insights into managing this persistent liver condition caused by the hepatitis B virus (HBV), which the World Health Organization reports affects 254 million people globally and results in approximately 1.1 million deaths annually.

The study focuses on the efficacy of two investigational treatments, tobevibart and elebsiran, administered with or without pegylated interferon alpha (PEG-IFNα). Participants in the trial received tobevibart at a dose of 300 mg every four weeks and elebsiran at 200 mg every four weeks, with an additional weekly dose of 180 µg for those receiving PEG-IFNα. Among the participants, the primary endpoint was the proportion achieving undetectable levels of hepatitis B surface antigen (HBsAg) at 24 weeks following the end of treatment.

At the conclusion of the study's first phase, 17% of participants treated with tobevibart and elebsiran without PEG-IFNα, and 21% with PEG-IFNα, achieved the primary endpoint of HBsAg loss. When considering all participants, these figures adjusted to 8% and 16%, respectively. Additionally, the concept of a functional cure, denoting sustainable undetectable HBsAg and HBV DNA levels after ceasing NRTI treatment, was achieved by 11% of those treated without PEG-IFNα and 15% with PEG-IFNα among participants with HBsAg levels below 1000 IU/mL.

The trial also explored a modified version of the functional cure that accounted for brief viral blips, allowing transient viral presence without undermining the treatment's success. Results for this variant showed cure rates of 11% and 23% for treatments without and with PEG-IFNα, respectively, among participants with low baseline HBsAg levels. For the broader participant group, the corresponding figures were 6% and 13%.

Safety and tolerability profiles for tobevibart and elebsiran remained consistent with prior studies, affirming that the combination is generally well-tolerated with only mild to moderate adverse events reported. Dr. Mark Eisner, Chief Medical Officer at Vir Biotechnology, highlighted that these findings enhance understanding of achieving a functional cure in CHB, offering vital insights for future treatment strategies.

However, while the results are promising, Vir Biotechnology has announced that advancing to Phase 3 development of the combination therapy for CHB will require a global development and commercialization partner, which has yet to be secured. The company intends to streamline the remaining stages of the MARCH Phase 2 program, ensuring participant safety and benefit while adhering to financial guidelines, with cash runway projections extending into mid-2027.

Vir Biotechnology remains dedicated to developing treatments for chronic hepatitis delta with tobevibart and elebsiran, given the promising potential to significantly suppress the hepatitis delta virus. This commitment is supported by positive data from the Phase 2 SOLSTICE trial, which demonstrated the combination's effectiveness and safety.

Tobevibart, a monoclonal antibody targeting HBsAg, is designed to prevent HBV and hepatitis delta virus entry into liver cells, while elebsiran, an siRNA developed by Alnylam Pharmaceuticals, aims to reduce hepatitis B virus RNA levels. Both treatments, currently under clinical investigation for hepatitis delta, offer innovative approaches to challenging infectious diseases. Meanwhile, Vir Biotechnology continues its broader mission to develop transformative medicines for serious infectious diseases and cancer.