In Vir Biotechnology’s phase 2 Solstice study, 66% of participants with chronic hepatitis delta (CHD) receiving a monthly dose of combination tobevibart and elebsiran achieved undetectable hepatitis delta virus (HDV) RNA at Week 48.
During the AASLD’s The Liver Meeting, Vir Biotechnology announced new 48-week results from its phase 2 Solstice demonstrating that a once-monthly combination of tobevibart and elebsiran delivered robust and sustained virologic responses in people with chronic hepatitis delta (CHD), including those with cirrhosis and high baseline viral loads. Along with being presented at the ongoing meeting, the data was published simultaneously in the New England Journal of Medicine, and underscore the regimen’s potential to address one of the most severe chronic viral infections.
"Achieving undetectable HDV RNA is a key endpoint in clinical trials, and HDV RNA undetectability is associated with better outcomes for people living with chronic hepatitis delta,” Tarik Asselah, MD, PhD, professor of Hepatology at the Hôpital Beaujon, APHP, Clichy, France, and at the University of Paris-Cité, and Head of the unit Viral Hepatitis UMR1149 at INSERM, France, said in a statement. “The combination of tobevibart and elebsiran has consistently demonstrated impressive hepatitis delta virologic suppression in the Solstice phase 2 trial, and these 48-week data are encouraging as they continue to support its potential to deliver meaningful patient benefit.”
According to the analysis, 66% (21/32) of participants achieved sustained hepatitis delta virus (HDV) RNA target not detected (TND) at Week 48. Nearly 90% reached hepatitis B surface antigen (HBsAg) levels below 10 IU/mL, indicating suppression of biological mechanisms necessary for HDV replication. Additionally, alanine aminotransferase (ALT) levels normalized in 56% of participants. The combination therapy was well tolerated, with no grade 3 or higher treatment-related adverse events or treatment discontinuations.
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CHD remains the most severe form of chronic viral hepatitis, recently classified as carcinogenic and associated with rapid progression to cirrhosis, liver failure, and liver-related mortality. With no approved therapies in the US and limited options worldwide, the combination therapy has received Breakthrough Therapy and Fast Track designations from the FDA and PRIME and orphan designations from the EMA.
Two-thirds of participants achieved sustained HDV RNA undetectability at 48 weeks, with broad improvements across liver and viral biomarkers.
No severe treatment-related adverse events were reported, and most side effects were mild and transient.
The therapy is now in phase 3 evaluation through Vir’s ECLIPSE program, supported by multiple global regulatory designations due to high unmet need.
The ECLIPSE program is a global registrational effort evaluating the safety and efficacy of combining tobevibart with elebsiran for the treatment of chronic hepatitis delta (CHD). It consists of three randomized, controlled clinical trials comparing the combination therapy with either deferred treatment or bulevirtide.
Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen (HBsAg). Designed to block the entry of hepatitis B and hepatitis delta viruses into liver cells, it also aims to reduce circulating viral and subviral particles. Discovered using Vir Biotechnology’s monoclonal antibody platform, tobevibart features an engineered Fc domain to enhance immune engagement and incorporates Xencor’s Xtend™ technology to prolong half-life. It is administered subcutaneously and is in clinical development for chronic hepatitis delta.
Elebsiran is an investigational small interfering RNA (siRNA) therapy developed by Alnylam Pharmaceuticals, Inc., designed to degrade hepatitis B virus RNA transcripts and reduce hepatitis B surface antigen production. Emerging data suggest direct antiviral activity against both hepatitis B and hepatitis delta viruses. Elebsiran is administered subcutaneously and is also in clinical development for chronic hepatitis delta.
The tobevibart-elebsiran combination is now advancing through Vir’s ECLIPSE registrational program, which includes three randomized, controlled Phase 3 trials. Enrollment for ECLIPSE 1 is already complete, and topline results from all three studies are anticipated in the first quarter of 2027.
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