Vir Biotechnology’s sidelined hepatitis B candidate, designed to serve as a “functional cure,” has failed to achieve the efficacy results hoped for in a midstage study.
The investigational combo of Vir’s monoclonal antibody tobevibart and Alnylam-discovered siRNA elebsiran was measured in a phase 2 trial for patients with chronic hepatitis B (CHB). Participants received the combo with or without pegylated interferon alpha (PEG-IFNα), a medication used to fight off CHB. Patients were placed into one of 13 specific cohorts, according to ClinicalTrials.gov.
The primary efficacy endpoint was proportion of participants with HBsAg seroclearance—known as undetectable HBsAg—at 24 weeks after treatment. No specific subgroup measures were defined in the primary endpoint.
Tobevibart and elebsiran treatment was tied to HBsAg loss in 8% (four of 51) of patients without PEG-IFNα and 16% (five of 32) for those receiving PEG-IFNα.
The biotech did not share whether the results met the primary endpoint or were statistically significant in the release.
When asked by Fierce whether the study missed the efficacy endpoint, a Vir spokesperson said that “the proportions of participants maintaining HBsAg seroclearance post-end of treatment are below the rates we were looking for.”
Instead, Vir highlighted a subgroup of patients that already had a low baseline undetectable HBsAg.
The data show that tobevibart and elebsiran “can achieve and maintain HBsAg loss in a subset of participants with low baseline HBsAg levels,” Vir Chief Medical Officer Mark Eisner, M.D., said in the release.
Overall, two of 51 patients experienced a “functional cure,” defined as sustained undetectable HBsAg and HBV DNA at 24 weeks post-end of treatment after discontinuing nucleos(t)ide reverse transcriptase inhibitors.
One of the study’s other primary goals assessed the proportion of participants with serious adverse events. Vir said the combo’s safety profile is consistent with past studies, and, generally, only mild or moderate treatment-emergent adverse events were reported.
The biotech will now “streamline” the final stages of the midstage program, according to the release.
Previously, the company said the investigational combo reduced hepatitis B surface antigens—one of the study’s four primary endpoints. At the time, Vir said it would not be moving the asset into phase 3 trials without help from a partner.
The biotech has yet to find said partner, leaving the future of the program suspended indefinitely.
Instead, Vir is focused on launching late-stage studies for the tobevibart-elebsiran combo in hepatitis D. Early efficacy results from a phase 2 trial last summer suggested that the pair may pose a threat to Gilead Sciences' faltering attempt to capture the hepatitis D market.