Vir Biotechnology has announced positive results from its Phase 2 SOLSTICE trial, evaluating tobevibart alone, or in combination with elebsiran, for chronic hepatitis delta (CHD). The combination therapy demonstrated 100% virologic response and rapid hepatitis delta virus (HDV) RNA suppression. These findings, presented at The Liver Meeting, support the initiation of a Phase 3 registrational program (ECLIPSE) in the first half of 2025.
SOLSTICE Trial Results
The SOLSTICE trial evaluated tobevibart monotherapy and a combination of tobevibart and elebsiran in CHD patients. Key findings include:
- Virologic Suppression: 100% of participants in the combination arms achieved HDV RNA reduction ≥2 log10 or below the limit of detection (LOD) at Week 24, sustained through Week 60.
- Undetectable HDV RNA: 41% of participants achieved undetectable HDV RNA at Week 24, increasing to 64% by Week 36 and 80% by Week 60 in a rollover cohort.
- HBsAg Reduction: Approximately 90% of participants receiving the combination achieved reductions in hepatitis B surface antigen (HBsAg) values below <10 IU/mL at Week 24.
- ALT Normalization: ALT levels normalized in 47% of participants in the combination de novo cohort and 56% in the rollover cohort by Week 24.
- Combined Endpoint: The combined endpoint of HDV RNA decrease ≥ 2 log10 or HDV RNA below LOD and ALT normalization at Week 24 was observed in 47% of participants in the combination de novo arm.
Tarik Asselah, M.D., Ph.D., Professor of Hepatology at the Hôpital Beaujon, APHP, Clichy, France, commented, "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, and I am excited to see this combination advance into a registrational Phase 3 program."
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. No ALT flares or study-related discontinuations were observed in the combination arms.
Phase 3 ECLIPSE Program
Following discussions with the FDA, Vir Biotechnology has finalized the design of the Phase 3 ECLIPSE program. This program will evaluate the tobevibart and elebsiran combination in CHD patients across three randomized, controlled trials, comparing the combination therapy to deferred treatment or bulevirtide. The program is set to commence in the first half of 2025.
- ECLIPSE 1: Will assess the efficacy and safety of tobevibart and elebsiran compared to deferred treatment.
- 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.
About Chronic Hepatitis Delta
Chronic Hepatitis Delta (CHD) is a severe form of chronic viral hepatitis caused by HDV. It affects millions worldwide 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 therapies.
About Tobevibart and Elebsiran
Tobevibart is a monoclonal antibody targeting the hepatitis B surface antigen, designed to inhibit viral entry and reduce viral particle levels. Elebsiran is a siRNA designed to degrade hepatitis B virus RNA transcripts and limit HBsAg production. Both are administered subcutaneously and are being evaluated for chronic hepatitis B as well.
