Long-term trial results raise hopes for new hepatitis D treatment approach
SOLSTICE trial data highlight sustained responses with tobevibart plus elebsiran
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After about two years of treatment with the experimental therapies tobevibart and elebsiran, nearly nine out of 10 evaluable patients had no detectable hepatitis D virus (HDV) in their blood.
That’s according to new data from the Phase 2 SOLSTICE clinical trial (NCT05461170), announced by Vir Biotechnology, the therapies’ developer.
“The latest data from our SOLSTICE Phase 2 trial evaluating tobevibart and elebsiran combination therapy in [chronic hepatitis D] are very promising, showing that monthly treatment with this combination therapy has the potential to achieve an undetectable viral load in a large number of patients, which could redefine the standard of care in [chronic hepatitis D],” Marianne De Backer, PhD, Vir’s CEO, said in a company press release.
Understanding hepatitis D and why it can be so serious
Hepatitis refers to liver inflammation. One of the most common causes is infection with the hepatitis B virus (HBV). Hepatitis D virus (HDV) is unusual because it can only infect people who already have HBV.
This type of co-infection tends to lead to worse outcomes. On average, people with chronic hepatitis D may progress to cirrhosis (irreversible liver scarring) and liver failure within about five years, according to Vir.
Tobevibart is an antibody designed to help block HBV and HDV viral particles from entering cells. Elebsiran is an RNA-based therapy designed to shut down the production of hepatitis B proteins that HDV needs to replicate. Both therapies are given as injections under the skin.
The SOLSTICE trial enrolled 95 adults with chronic HDV infection, including people with and without cirrhosis. Most participants were randomly assigned to receive tobevibart plus elebsiran every month, or tobevibart every two weeks.
Some participants also received elebsiran alone or a different dosing schedule of tobevibart, but many later transitioned to the combination group.
Results published late last year showed that after about one year, 66% of patients treated with tobevibart plus elebsiran had no detectable HDV genetic material in their blood, compared with 48% of those treated with tobevibart alone.
A combined response, defined as undetectable HDV plus normalization of a marker of liver damage, was achieved after about one year in 56% of patients given the combination therapy and 61% of those given tobevibart alone.
New follow-up data show sustained viral suppression at two years
Vir has now announced additional follow-up data for some participants at 72 weeks (about 1.5 years) and 96 weeks (about two years).
Among participants given the combination, 24 out of 31 (77%) had no detectable HDV genetic material at 72 weeks, and 21 of 24 (88%) had no detectable HDV genetic material at 96 weeks. Among those treated with tobevibart alone, the rates were 53% at week 72 and 46% at week 96.
Vir reported that most safety findings have been mild to moderate and temporary, and that no serious safety concerns have been reported in patients given the combination.
The company is now running three clinical trials, called the ECLIPSE program, to further evaluate the safety and effectiveness of the investigational combination therapy for HDV.
The Phase 3 ECLIPSE 1 trial (NCT06903338) has completed enrollment and is comparing the combination therapy with delayed treatment. Top-line data are expected by the end of the year.
The Phase 2b ECLIPSE 3 trial (NCT07142811) is testing the combination against bulevirtide, which is approved in Europe for chronic hepatitis D. The Phase 3 ECLIPSE 2 trial (NCT07128550) is evaluating the combination in people who still have detectable HDV genetic material despite treatment with bulevirtide.
ECLIPSE 3 has also completed enrollment, and top-line data from ECLIPSE 2 and ECLIPSE 3 are expected in early 2027.
