Vir Biotechnology 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 rapid and sustained virologic suppression, with plans to advance the combination into a Phase 3 registrational program (ECLIPSE) in the first half of 2025.
The investigational combination of tobevibart, a human monoclonal antibody, and elebsiran, an siRNA, achieved 100% virologic response with monthly dosing. At Week 24, 41% of participants achieved undetectable hepatitis delta virus (HDV) RNA, which rose to 64% by Week 36 and 80% by Week 60 in a subset of participants.
SOLSTICE Trial Results
The SOLSTICE trial randomized participants to 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 rolled over to receive the combination therapy. Virologic suppression rates were assessed at Week 24 and monitored through Week 60.
Key findings include:
- 100% of participants in the combination arms achieved at least a 2 log10 decrease in HDV RNA or below the limit of detection at Week 24, sustained through Week 60.
- HDV RNA was undetectable in 41% of participants at Week 24, increasing to 64% at Week 36 and 80% at Week 60 in the rollover cohort.
- Approximately 90% of participants receiving the combination achieved reductions in hepatitis B surface antigen (HBsAg) values below <10 IU/mL at Week 24.
- ALT levels normalized in 47% of participants in the combination de novo cohort and 56% in the rollover cohort by Week 24.
The combined endpoint of HDV RNA decrease ≥ 2 log10 or below the limit of detection 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 not detected and ALT normalization was achieved in 19% of participants in the combination de novo arm at Week 24, increasing to 27% by Week 36.
Safety and Tolerability
The combination therapy demonstrated a favorable safety profile, with treatment-emergent adverse events generally mild or moderate and transient. Influenza-like illness was the most common event. No ALT flares, study-related discontinuations, or treatment-related severe adverse events were reported.
Phase 3 ECLIPSE Program
Following discussions with the FDA, Vir Biotechnology finalized the design of the Phase 3 ECLIPSE program, which will 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. The trials will enroll both cirrhotic and non-cirrhotic participants.
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.”
About Chronic Hepatitis Delta
Chronic hepatitis delta (CHD) is a severe form of chronic viral hepatitis, caused by the hepatitis delta virus (HDV). It affects an estimated 5% of people with chronic hepatitis B. CHD accelerates progression to cirrhosis and liver failure, with limited treatment options currently available in the United States.
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.”
