Vir’s chronic hepatitis D treatment reduced the presence of the virus RNA as well as normalized certain liver enzyme levels across 24 weeks in a mid-stage test.
In the Phase 2 SOLSTICE study, some patients were given Vir’s monoclonal antibody tobevibart and a small interfering ribonucleic acid called elebsiran as a combination once a month, while others received tobevibart twice a month as a monotherapy. Hepatitis D is the most severe form of viral hepatitis and there is no approved treatment in the US.
After 24 weeks, all 11 participants who took the combo saw a reduction of HDV RNA levels, indicative of the amount of virus present, according to preliminary data shared Wednesday at the EASL International Liver Congress.
All of these patients hit the lower limit of quantification for virus levels, while 91% (10 out of 11) achieved an even lower virus level, which is referred to as “the lower limit of detection.” In more than half of participants (55%; 6 out of 11), the virus couldn’t be detected at all.
Also, 64% of patients saw normalized levels of alanine aminotransferase — high levels of this liver enzyme are a sign of liver damage and one of the hallmarks of hepatitis D.
Meanwhile, in 11 patients given the tobevibart monotherapy, 55% of patients (6 out of 11) saw a decrease in virus levels, while 64% had normalized ALT levels. A little over half (55%; 6 out of 11) hit the lower limit of quantification — 46% (5 out of 11) hit the lower limit of detection levels, and in 18% (2 out of 11) the virus couldn’t be detected.
“These are preliminary data, of course, in a limited set of participants, but impressive responses both on a virological and on the ALT normalizations side,” Vir CEO Marianne De Backer told Endpoints News in an interview. Vir will share more results that include all 60 trial participants after 24 weeks of treatment in the fourth quarter of this year.
Wednesday’s data come after the initial SOLSTICE data shared last year in just six patients, who received 12 weeks of either tobevibart or elebsiran monotherapy and then rolled over into the combo arm of the trial. All of the patients are still on the treatment, according to Vir, and 80% reached undetectable status after 48 weeks.
Leerink analysts wrote that if Vir’s combo therapy can replicate the efficacy seen in the initial SOLSTICE results — 80% of patients reaching undetectable status with the virus — in a larger cohort of patients “this could bolster investor conviction in the program & support advancement into a Ph.3.” The analysts added company management believes that if the combo replicates 80% of the full data, it could potentially set a new bar for efficacy.
The market opportunity in hepatitis D is “large,” with Leerink analysts predicting about 100,000 patients in the US and 200,000 in the EU, with some literature suggesting there are 48 to 60 million patients globally. Gilead’s Hepcludex is the only approved therapy for the virus in the EU but it requires daily injections and “its efficacy profile likely leaves room for improvement,” they added.
De Backer said that its combo approach is a “two-pronged attack” against the virus. The antibody tobevibart works by preventing the virus from entering cells and allows for an immune system response. Then, elebsiran acts by “basically dicing up RNA transcripts from the virus” and reducing levels of antigen, which is what the virus needs for replication.
Editor’s Note: This story has been updated to clarify the number of potential patients in the US and EU.