Vir Biotechnology, Inc. (NASDAQ:VIR) has announced positive results from its Phase 2 SOLSTICE clinical trial, evaluating tobevibart alone, or in combination with elebsiran, for treating chronic hepatitis delta (CHD). The combination therapy demonstrated a 100% virologic response and rapid suppression of hepatitis delta virus (HDV) RNA when administered monthly.
The data, presented at The Liver Meeting of the American Association for the Study of Liver Diseases (AASLD), showed that HDV RNA was undetectable in 41% of participants at Week 24, increasing to 64% by Week 36. By Week 60, 80% of participants in one cohort achieved undetectable HDV RNA.
Based on these results and discussions with the FDA, Vir Biotechnology plans to initiate the Phase 3 ECLIPSE program in the first half of 2025 to further assess the combination of tobevibart and elebsiran for CHD treatment.
SOLSTICE Trial Results
The Phase 2 SOLSTICE trial randomized participants to receive either tobevibart 300 mg monotherapy every two weeks (n=33) or a combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (n=32). Participants from previous monotherapy cohorts could also rollover to receive the combination therapy (n=13).
Key findings include:
- Rapid and Sustained Virologic Suppression: 100% of participants in the combination arms achieved at least a 2 log10 decrease in HDV RNA or below the limit of detection (LOD) at Week 24, 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% at Week 60 in the rollover cohort.
- Hepatitis B Surface Antigen (HBsAg) Reduction: Approximately 90% of participants receiving the combination achieved HBsAg 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, 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.
Safety Profile
The combination of tobevibart and elebsiran demonstrated a favorable safety profile, consistent with previous studies. Treatment-emergent adverse events (TEAEs) were generally mild or moderate and transient, with influenza-like illness being the most common. No ALT flares or study-related discontinuations were observed in the combination arms, and no treatment-related severe adverse events (SAEs) were reported.
ECLIPSE Phase 3 Program
The Phase 3 ECLIPSE program will evaluate the tobevibart and elebsiran combination in people with CHD. The program includes three randomized, controlled trials comparing the combination therapy to deferred treatment or bulevirtide. All studies will enroll both cirrhotic and non-cirrhotic participants.
- ECLIPSE 1: Assesses efficacy and safety of tobevibart and elebsiran compared to deferred treatment.
- ECLIPSE 2: Evaluates 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 comparing tobevibart and elebsiran with bulevirtide in bulevirtide-naïve patients.
About Hepatitis Delta
Chronic hepatitis delta (CHD) is a severe form of chronic viral hepatitis caused by HDV. It can lead to cirrhosis and liver failure within 5 years. There is currently no approved treatment for CHD in the United States.
"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. "New, effective therapeutic options are urgently needed, and I am excited to see this combination advance into a registrational Phase 3 program."
Regulatory Designations
The FDA granted fast track designation for the combination of tobevibart and elebsiran for CHD treatment in June 2024. The EMA also issued a positive opinion on the application for orphan drug designation for the combination.
