Vir Biotechnology’s ‘functional cure’ combination therapy has failed to meet the efficacy endpoints in a Phase II trial in hepatitis B.
The company reported data from the 24-week point of the ongoing MARCH Phase II trial (NCT04856085) where just 17% (3/18) and 21% (3/14) of patients with baseline hepatitis B surface antigen (HBsAg) <1,000IU/mL receiving tobevibart and elebsiran without or with peginterferon, respectively, achieved undetectable HBsAg.
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The trial also evaluated tobevibart and elebsiran without or with peginterferon as a functional cure. This was achieved in 11% and 15% of patients, respectively.
Functional cure for hepatitis B is defined as sustained undetectable HBsAg and hepatitis B virus DNA below the lower limit of quantification (0.05IU/mL) at 24 weeks post-end of treatment after discontinuing nucleoside reverse transcriptase inhibitors (NRTIs).
The study also looked at a modified definition of functional cure that allowed brief increases in virus levels for up to 35 days. Using this measure, 11% of patients treated with tobevibart and elebsiran alone, and 23% of those who also received peginterferon, showed signs of a functional cure.
Vir said the safety and tolerability profile of tobevibart and elebsiran remains consistent with prior studies.
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By GlobalDataPreviously, Vir said the investigational combo reduced hepatitis B surface antigens at the same 24-week time stamp.
Chronic hepatitis B is a long-lasting, inflammatory liver disease caused by the hepatitis B virus. The World Health Organization estimates that 254 million people live with hepatitis B, and an estimated 1.1 million deaths a year are associated with the disease. Complications may include liver cirrhosis, liver failure and liver cancer.
Vir Biotechnology presented the data at the 2025 European Association for the Study of the Liver (EASL) congress in Amsterdam.
Combination also evaluated in hepatitis D
Tobevibart is a monoclonal antibody developed by Vir while elebsiran is an Alnylam-discovered siRNA.
In a Phase II trial (NCT05461170) in hepatitis D, the combination was more effective, with all six patients showing sustained virologic response at the time of the last visit and all patients achieving hepatitis D virus RNA < limit of detection (LOD) or ≥ 2 log10 IU/mL decrease from baseline.
Vir Biotechnology is waiting to gain a partner to advance the combination therapy to Phase III studies. A Phase III trial of the combination in hepatitis D is currently recruiting patients (NCT06903338).
