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A **combination investigational therapy** for chronic hepatitis B, consisting of **elebsiran** (a GalNAc-conjugated small interfering RNA targeting HBV RNA), **tobevibart** (a broadly neutralizing monoclonal antibody directed against hepatitis B surface antigen/HBsAg), and **pegylated interferon alfa** (a recombinant human interferon conjugated with polyethylene glycol to augment half-life and immunomodulatory effects). - **Mechanisms of action**: - Elebsiran (VIR-2218) targets conserved sequences of the HBV genome, reducing viral RNA and surface antigen levels, delivered hepatocyte-specifically via GalNAc conjugation[7][1][4][5]. - Tobevibart (VIR-3434) binds to and neutralizes HBsAg, inhibiting entry and spread of HBV and HDV in the liver, and is engineered (Xtend technology) for increased immune engagement and half-life[2][4][7]. - Pegylated interferon alfa stimulates the innate antiviral response via activation of the JAK/STAT pathway, upregulating effector proteins and immunomodulation[3][6]. - **Indication**: This combination is being evaluated in Phase 2 trials for **chronic hepatitis B** aiming for “functional cure” (sustained off-treatment HBsAg loss and HBV DNA suppression), with additional trials for chronic hepatitis delta[1][4][5][7]. - **Developers**: Vir Biotechnology (VIR-2218, VIR-3434), Roche (pegylated interferon alfa/Pegasys)[1][3][6][7]. - **Route of administration**: All drugs in the combination are administered **subcutaneously**[2][3][5].
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