Vir Biotechnology has announced positive results from its SOLSTICE Phase 2 clinical trial, evaluating the combination of tobevibart and elebsiran for the treatment of chronic hepatitis delta (CHD). The trial achieved a 100% virologic response, demonstrating significant HDV RNA suppression in participants. These findings pave the way for a Phase 3 registrational program, ECLIPSE, slated to begin in early 2025.
The SOLSTICE trial's results, presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting, revealed that the combination therapy led to undetectable virus levels in 41% of participants at Week 24, which increased to 64% by Week 36 and reached 80% by Week 60. This indicates a sustained and increasing viral clearance over time.
Key Findings from the SOLSTICE Trial
The Phase 2 SOLSTICE trial randomized participants to receive either tobevibart monotherapy (300 mg every two weeks) or a combination of tobevibart (300 mg) and elebsiran (200 mg) every four weeks. Some participants from previous monotherapy cohorts were also rolled over to receive the combination therapy. Virologic suppression rates were assessed at Week 24 and further evaluated 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 levels below the limit of detection (LOD) at Week 24, a rate that was sustained through Week 60.
- HDV RNA Target Not Detected (TND): 41% of participants achieved HDV RNA TND at Week 24, increasing to 64% at Week 36 and 80% in the rollover cohort by Week 60.
- Hepatitis B Surface Antigen (HBsAg) Reduction: Approximately 90% of participants receiving the combination therapy achieved HBsAg levels below 10 IU/mL at Week 24, indicating suppression of key viral replication mechanisms.
- ALT Normalization: Alanine aminotransferase (ALT) levels decreased in most participants, with normalization observed in 47% of the de novo cohort and 56% of the rollover cohort by Week 24. These rates were sustained at Week 36.
Safety and Tolerability
The combination therapy demonstrated a strong safety profile, with treatment-emergent adverse events (TEAEs) generally mild or moderate and transient. Influenza-like illness was the most common event. Notably, no ALT flares, study-related discontinuations, or treatment-related severe adverse events (SAEs) were reported in the combination arms.
Implications for CHD Treatment
Chronic hepatitis delta is the most severe form of chronic viral hepatitis, often leading to cirrhosis and liver failure within 5 years. Currently, there is no approved treatment for CHD in the United States, highlighting a significant unmet medical need. The combination of tobevibart and elebsiran offers a potential solution by targeting the viral lifecycle through multiple mechanisms.
"Achieving HDV RNA suppression with a safe, well-tolerated, and conveniently dosed treatment could be transformative for people living with hepatitis delta," said Tarik Asselah, M.D., Ph.D., Professor of Hepatology at the Hôpital Beaujon, APHP, Clichy, France, and at the University of Paris-Cité. "New, effective therapeutic options are urgently needed, and I am excited to see this combination advance into a registrational Phase 3 program."
Phase 3 ECLIPSE Program
Vir Biotechnology plans to initiate the Phase 3 registrational ECLIPSE program in the first half of 2025. The program will consist of three randomized, controlled trials designed to evaluate the combination therapy against deferred treatment or bulevirtide. The trials will enroll both cirrhotic and non-cirrhotic participants.
- ECLIPSE 1: Will assess the efficacy and safety of tobevibart and elebsiran compared to deferred treatment in regions where bulevirtide is not available or its use is limited.
- ECLIPSE 2: Will evaluate the efficacy and safety of switching to tobevibart and elebsiran in people with CHD who have not achieved viral suppression with bulevirtide therapy.
- ECLIPSE 3: A Phase 2b head-to-head trial to evaluate tobevibart and elebsiran compared with bulevirtide in bulevirtide-naïve patients.
Regulatory Designations
The FDA granted fast track designation for the combination of tobevibart and elebsiran in June 2024. Additionally, the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) issued a positive opinion on the application for orphan drug designation for the treatment of CHD.
