Vir Biotechnology has announced positive results from its Phase 2 SOLSTICE trial, evaluating tobevibart, a human monoclonal antibody, in combination with elebsiran, an siRNA, for the treatment of chronic hepatitis delta (CHD). The trial demonstrated a 100% virologic response and rapid suppression of hepatitis delta virus (HDV) RNA with monthly dosing.
The data, presented at The Liver Meeting of the American Association for the Study of Liver Diseases (AASLD), showed that 41% of participants achieved HDV RNA levels below the lower limit of quantification (TND) at Week 24, which increased to 64% by Week 36. In a cohort that reached Week 60, 80% achieved HDV RNA TND, indicating significant viral clearance.
Key Findings from the SOLSTICE Trial
The SOLSTICE trial randomized participants to receive either tobevibart 300 mg monotherapy every two weeks or a combination of tobevibart 300 mg and elebsiran 200 mg every four weeks. Participants from previous monotherapy cohorts were also allowed to roll over to receive the combination therapy. Virologic suppression rates were evaluated at Week 24 and further assessed at Weeks 36, 48, and 60.
- Virologic Suppression: 100% of participants in the combination arms achieved at least a 2 log10 decrease in HDV RNA or HDV RNA below the limit of detection at Week 24, which was sustained over time.
- Hepatitis B Surface Antigen Reduction: Approximately 90% of participants receiving the combination achieved reductions in hepatitis B surface antigen values below 10 IU/mL at Week 24, with sustained responses at later time points.
- ALT Normalization: Alanine aminotransferase (ALT) levels decreased in most participants between Day 1 and Week 24, normalizing in 47% of participants in the combination de novo cohort and 56% in the rollover cohort by Week 24. These rates were sustained at Week 36.
- Composite Endpoint: The protocol-defined combined endpoint of HDV RNA decrease ≥2 log10 compared to baseline or HDV RNA below LOD and ALT normalization at Week 24 was observed in 47% of participants in the combination de novo arm. The more stringent composite endpoint of HDV RNA TND and ALT normalization was achieved in 19% of participants in the combination de novo arm at Week 24, increasing to 27% by Week 36. This trend was reflected in the combination rollover cohort, where 33% of participants achieved this endpoint at Week 24 and 40% at Week 60.
Safety and Tolerability
The safety profile of tobevibart and elebsiran was consistent with previous studies. Treatment-emergent adverse events were generally mild or moderate and transient across all treatment groups, with influenza-like illness being the most common. No ALT flares were observed, and there were no study-related discontinuations in the combination arms, nor any treatment-related severe adverse events reported.
Planned Phase 3 ECLIPSE Program
Following a meeting with the FDA, Vir Biotechnology has finalized the design of the Phase 3 registrational clinical program, ECLIPSE, which will evaluate the tobevibart and elebsiran combination in people living with CHD. The program, set to commence in the first half of 2025, will include three randomized, controlled trials designed to evaluate the combination therapy in comparison to deferred treatment or bulevirtide. All studies will enroll both cirrhotic and non-cirrhotic participants.
ECLIPSE 1 and 2 are Phase 3 trials designed to provide the registrational efficacy and safety data needed for submission to global regulatory agencies. ECLIPSE 3 is a Phase 2b trial designed to provide important supportive data, particularly in Europe, to help establish appropriate pricing and reimbursement in key markets.
