Vir Biotechnology's Hepatitis B 'Functional Cure' Candidate Falls Short in Phase 2 Trial

Vir Biotechnology's ambitious attempt to develop a "functional cure" for chronic hepatitis B (CHB) has hit a significant roadblock, as its investigational combination therapy failed to meet efficacy expectations in a recent phase 2 clinical trial. The setback raises questions about the future of this particular approach to treating CHB and highlights the ongoing challenges in developing effective therapies for this persistent viral infection.

Trial Results and Efficacy Concerns

The phase 2 study evaluated a combination of Vir's monoclonal antibody tobevibart and Alnylam-discovered siRNA elebsiran, with and without pegylated interferon alpha (PEG-IFNα). The primary efficacy endpoint focused on the proportion of participants achieving HBsAg seroclearance, or undetectable hepatitis B surface antigen, at 24 weeks post-treatment.

Results showed that HBsAg loss occurred in 8% (4 out of 51) of patients treated without PEG-IFNα and 16% (5 out of 32) of those receiving PEG-IFNα. However, these outcomes fell short of the company's expectations. A Vir spokesperson acknowledged that "the proportions of participants maintaining HBsAg seroclearance post-end of treatment are below the rates we were looking for."

Despite the overall disappointing results, Vir highlighted a subset of patients with low baseline HBsAg levels who showed more promising outcomes. Dr. Mark Eisner, Vir's Chief Medical Officer, stated that the data demonstrate the combination's ability to "achieve and maintain HBsAg loss in a subset of participants with low baseline HBsAg levels."

Implications for Vir's Hepatitis B Program

The underwhelming efficacy results have significant implications for Vir's hepatitis B program. The company had previously indicated that it would not advance the tobevibart-elebsiran combination into phase 3 trials without a partner. Given the current results, finding such a partner may prove challenging, potentially leaving the program's future in limbo.

Vir has announced plans to "streamline" the final stages of the midstage program, though details on what this entails remain unclear. The company's focus appears to be shifting towards other potential applications of the investigational combo, particularly in treating hepatitis D.

Early efficacy results from a separate phase 2 trial last summer suggested that the tobevibart-elebsiran combination might be a promising contender in the hepatitis D market, potentially challenging Gilead Sciences' efforts in this area. This alternative avenue may offer Vir a path forward for its investigational therapy, despite the setback in hepatitis B.