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 chronic hepatitis delta (CHD). The combination therapy demonstrated a 100% virologic response and rapid suppression of the hepatitis delta virus (HDV). These findings, presented at The Liver Meeting of the American Association for the Study of Liver Diseases (AASLD), support the initiation of a Phase 3 registrational program (ECLIPSE) in the first half of 2025.
CHD is a severe form of chronic viral hepatitis, affecting millions worldwide. It is caused by the hepatitis delta virus (HDV) and can lead to cirrhosis and liver failure within 5 years. There is currently no approved treatment for CHD in the United States, highlighting the urgent need for effective therapeutic options.
Tarik Asselah, M.D., Ph.D., Professor of Hepatology at the Hôpital Beaujon, APHP, Clichy, France, emphasized the potential impact of the treatment: "Achieving HDV RNA suppression with a safe, well-tolerated, and conveniently dosed treatment could be transformative for people living with hepatitis delta...New, effective therapeutic options are urgently needed".
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 (combination de novo arm, n=32). Additionally, participants from previous tobevibart or elebsiran monotherapy cohorts could rollover to receive the combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination rollover, n=13). Virologic suppression rates were assessed at Week 24 and further monitored at Weeks 36, 48, and 60.
Key findings from the trial include:
- Rapid and Sustained Virologic Suppression: 100% of participants in the combination arms achieved an HDV RNA decrease ≥2 log10 or below the limit of detection (LOD) at Week 24, sustained through Week 60.
- Undetectable HDV RNA: 41% (13/32) of participants in the combination arms achieved undetectable HDV RNA at Week 24, increasing to 64% (14/22) at Week 36 and 80% (4/5) in the rollover cohort by Week 60.
- Hepatitis B Surface Antigen (HBsAg) Reduction: Approximately 90% of participants receiving the combination achieved HBsAg values below <10 IU/mL at Week 24, indicating suppression of key biologic mechanisms required for viral replication.
- ALT Normalization: Alanine aminotransferase (ALT) levels decreased in most participants between Day 1 and Week 24, normalizing in 47% (15/32) of participants in the combination de novo cohort and 56% (5/9) in the rollover cohort by Week 24. These rates were sustained at Week 36.
- Combined Endpoints: The 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% (15/32) of participants in the combination de novo arm. The more stringent composite endpoint of HDV RNA TND and ALT normalization was achieved in 19% (6/32) of participants in the combination de novo arm at Week 24, increasing to 27% (6/22) by Week 36.
Safety and Tolerability
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, study-related discontinuations, or treatment-related severe adverse events (SAEs) were reported.
ECLIPSE Phase 3 Program
Following discussions with the FDA, Vir Biotechnology has finalized the design of the Phase 3 registrational clinical program, ECLIPSE, to further evaluate the tobevibart and elebsiran combination in individuals with CHD. The program will consist of three randomized, controlled trials comparing the combination therapy to deferred treatment or bulevirtide. All studies will include both cirrhotic and non-cirrhotic participants.
The ECLIPSE program includes:
- ECLIPSE 1: Assessing 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: Evaluating the efficacy and safety of switching to tobevibart and elebsiran in individuals 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.
Regulatory Designations
The FDA has granted fast track designation to the combination of tobevibart and elebsiran for CHD treatment, aiming to expedite the development and review of drugs for serious conditions with unmet medical needs. Additionally, the EMA's Committee for Orphan Medicinal Products (COMP) has issued a positive opinion on the application for orphan drug designation for tobevibart and elebsiran in treating CHD.
Marianne De Backer, M.Sc., Ph.D., MBA, Chief Executive Officer of Vir Biotechnology, stated, "We are confident that our regimen has the potential to deliver transformative benefits for patients, and we will build on our strong SOLSTICE data to start our Phase 3 registrational ECLIPSE program as soon as possible in 2025."
