A combination treatment involving tobevibart and elebsiran significantly improved disease activity in adults with chronic hepatitis D, based on new data from the ongoing phase 2 SOLSTICE study. 

The study explores the safety and antiviral abilities of tobevibart, a monoclonal antibody, both alone and in combination with elebsiran, a small interfering RNA, for treating adults with chronic hepatitis delta infection with or without compensated cirrhosis, who were already on nucleoside or nucleotide reverse transcriptase inhibitors. Although tobevibart and elebsiran both target the hepatitis B virus surface antigen (HBsAg), their value in hepatitis delta virus (HDV) treatment remains unknown, the researchers said.

HDV infection, a severe form of the disease that occurs in those already infected with hepatitis B, has limited treatment options and can progress to even more severe disease, said Tarik Asselah, MD, of the Université de Paris-Cité, Hôpital Beaujon, Paris, France, and colleagues in a study presented at The Liver Meeting 2025: American Association for the Study of Liver Diseases (AASLD). The findings were simultaneously published in The New England Journal of Medicine.

The researchers randomly assigned 32 adults with HDV to a combination of tobevibart plus elebsiran every 4 weeks and 33 to monotherapy with tobevibart every 2 weeks. The combined primary endpoint was defined as either an HDV RNA level that was undetectably low, or a decrease of at least 2 log₁₀ IU/mL from baseline in HDV RNA levels. The mean age of the patients in the combination and tobevibart-only groups was 42 years and 45 years, respectively, approximately half were men, and more than 75% were White individuals.

After 24 weeks, 47% of patients who received the combination therapy and 70% of those who received only tobevibart met the primary endpoint; all patients in the combination group and 82% of those in the tobevibart-only group had a virologic response.

At 48 weeks, 56% of those in the combination group and 61% of those in the tobevibart-only group met the primary endpoint. Additionally, HBsAg levels below 10 IU/mL were attained by 91% of patients in the combination group and 21% of those in the tobevibart-only group.

The number of patients with at least one adverse event during the study period was similar between the combination and tobevibart-only groups (81% and 94%, respectively). The most commonly reported adverse events in both groups were chills and flu-like illness.

HDV requires the antigen HBsAg to multiply, the researchers wrote in their discussion of the findings. “In the SOLSTICE trial, an HBsAg level below 10 IU/mL (the target for HBV therapies) was observed in 91% of participants who received tobevibart plus elebsiran. This high incidence of response may be attributable to the complementary mechanisms of tobevibart and elebsiran,” they said.

The ongoing study is designed to assess safety and efficacy of tobevibart alone or in combination with elebsiran for up to 192 weeks. 

Small Steps Can Make a Big Difference in Treating HDV

The current study is important because there is as yet no approved treatment for HDV in the US, said Douglas T. Dieterich, MD, in an interview. The results offer hope for the treatment of HDV, the deadliest form of hepatitis, said Dieterich, director of the Institute for Liver Medicine at the Mount Sinai Health System and professor of medicine at the Icahn School of Medicine, New York City.

Another drug, bulevirtide, is approved for HDV in Europe and elsewhere, but it must be administered as a subcutaneous injection each day, Dieterich noted.

Although the new combination does not generate 100% response, it clearly has activity, Dieterich said. “Delta is a very difficult virus to treat, so any activity is a big help,” he said. 

More research is needed, and is ongoing, said Dieterich. A phase 3 study of tobevibart and elebsiran known as ECLIPSE 1 recently reached full enrollment, and early results are expected in 2027, according to a company press release.

The study was supported by Vir Biotechnology. Dieterich disclosed serving as a consultant for Vir but was not involved in this research.