Tobevibart is an engineered human monoclonal antibody against hepatitis B virus (HBV) surface antigen (HBsAg) that neutralizes both HBV and hepatitis delta virus (HDV) and is currently under clinical investigation for treating chronic hepatitis B and chronic hepatitis delta.
The antibody features a modified GAALIE Fc region that enhances its immunological properties beyond simple viral neutralization.
This engineered Fc increases binding to activating Fc gamma receptors (FcγRs) while decreasing binding to inhibitory FcγRIIb, which facilitates enhanced uptake of HBsAg by neutrophils and monocytes.
Tobevibart is an investigational, broadly neutralizing human monoclonal antibody directed against the hepatitis B surface antigen (HBsAg).
It is being developed for chronic hepatitis B and chronic hepatitis delta (HDV co‑infection), with the dual aims of blocking viral entry and facilitating functional cure via HBsAg clearance and immune re‑engagement.
Tobevibart targets HBsAg and neutralizes both HBV and HDV, preventing their entry into hepatocytes.
Its Fc region is engineered to enhance binding to activating Fcγ receptors, reduce binding to inhibitory FcγRIIb, and prolong half‑life.
These Fc changes promote immune complex formation with HBsAg, increased uptake by neutrophils and monocytes, dendritic cell activation, and improved HBsAg‑specific T‑cell responses, with associated reductions in circulating HBsAg in early clinical studies.
Tobevibart administration (e.g., 300 mg) can bind circulating HBsAg and reduce serum HBsAg, with evidence of enhanced antigen presentation and T‑cell responses.
In chronic hepatitis delta, the phase 2 SOLSTICE trial evaluated tobevibart alone and in combination with elebsiran (an HBV‑targeting siRNA that reduces HBsAg production) in non‑cirrhotic and compensated cirrhotic adults.
At 48 weeks, combination therapy with tobevibart plus elebsiran produced rapid and deep HDV suppression, driving HDV RNA to undetectable levels in a substantial proportion of patients, with an acceptable safety profile.
The combination of tobevibart and elebsiran has received FDA Therapy designation for chronic hepatitis delta.
Tobevibart is administered subcutaneously and remains investigational; it is not yet an approved therapy for HBV or HDV.
Across early HBV studies and the HDV SOLSTICE trial, reported treatment‑emergent adverse events have been mainly mild to moderate, with influenza‑like illness among the most common.
The safety profile of the tobevibart–elebsiran combination in SOLSTICE was similar across treatment groups and consistent with prior experience for each agent.
In clinical trials, administration of 300 mg tobevibart resulted in binding of HBsAg to these immune cells concurrent with reduction in circulating HBsAg levels.
The GAALIE modification also enables tobevibart to activate dendritic cells more effectively than wild-type Fc antibodies, leading to enhanced presentation of HBV antigens and stimulation of HBsAg-specific T cell responses.
This dual mechanism—combining potent viral neutralization with immune activation—distinguishes tobevibart from conventional antiviral approaches.
In a phase 2 trial for hepatitis D, tobevibart (300 mg subcutaneously every 2 weeks) combined with elebsiran (an siRNA targeting HBsAg production) demonstrated substantial reductions in HBsAg levels, with 91% of participants achieving HBsAg levels below 10 IU/mL at week 48.
The combination therapy produced mean HBsAg reductions of approximately 3.5 log10 IU/mL, compared to 1.8 log10 IU/mL with tobevibart monotherapy.