The combination therapy has received breakthrough therapy and fast track designations from the US Food and Drug Administration as well as PRIME and orphan drug status from the European Medicines Agency, signaling regulatory recognition of its potential in addressing a critical clinical gap.
In an email interview, Mark Eisner, MD, MPH, chief medical officer at Vir Biotechnology, addressed the unique challenges in treating chronic hepatitis D and the scientific rationale behind this investigational approach.
“Chronic hepatitis delta remains a silent and often overlooked disease, disproportionately affecting vulnerable groups most heavily concentrated in a few geographic hot spots where patients already face significant barriers to diagnosis and care,” said Eisner. “After enduring complex testing journeys, patients are met with very limited treatment options such as off-label pegylated interferon in the US, with challenging adverse effects, or daily subcutaneous injections of bulevirtide in the EU [European Union] and UK [United Kingdom].”
What You Need To Know
Vir Biotechnology has initiated the Phase 2b ECLIPSE 3 trial, comparing its investigational combination therapy tobevibart and elebsiran against bulevirtide in treatment-naïve chronic hepatitis delta patients.
The combination therapy uses two distinct mechanisms to target hepatitis B surface antigen, aiming to block viral entry and degrade viral RNA for dual antiviral effects.
The trial’s primary goal is to achieve complete viral suppression at Week 48, with monthly injections designed to improve treatment adherence and patient quality of life.
Eisner emphasized that the combination therapy of tobevibart and elebsiran is designed to offer a dual-targeted strategy.
“We are evaluating our investigational combination therapy of tobevibart and elebsiran for chronic hepatitis delta, which may offer a unique approach by targeting hepatitis B surface antigen through 2 distinct and complementary mechanisms,” he explained. “Tobevibart, an Fc-engineered monoclonal antibody, is designed to block viral entry and neutralize circulating virions. Elebsiran, a small interfering RNA, targets hepatitis B surface antigen production by degrading hepatitis B virus mRNA. By deploying these 2 complementary mechanisms, our regimen provides a comprehensive strategy for chronic hepatitis delta by addressing both hepatitis delta virus and hepatitis B virus replication simultaneously.”
Discussing the ECLIPSE 3 trial design, Eisner described the primary virologic end point and its clinical relevance.
“It is important to emphasize that head-to-head comparison data in a controlled clinical trial are the only way to evaluate potential superiority compared with current standards of care for chronic hepatitis delta,” Eisner noted. “The primary end point of ECLIPSE 3 is HDV [hepatitis D virus] RNA TND [target not detected] at week 48 after randomization, which means complete suppression of viral replication. We believe this is the most critical marker for efficacy and potentially the most predictive one for long-term liver-related outcomes such as cirrhosis, liver transplantation, or death.”
Vir is also evaluating how the monthly subcutaneous dosing of both tobevibart and elebsiran might improve real-world treatment adherence and patient experience.
“Tobevibart and elebsiran are being evaluated for the treatment of chronic hepatitis delta in clinical trials as monthly subcutaneous injections, reducing the treatment frequency from daily to monthly injections,” said Eisner. “We will be assessing impact on quality of life through patient-reported outcomes in our ECLIPSE clinical trial program.”
As Vir advances its ECLIPSE trials, the company aims to generate a comprehensive clinical evidence package supporting regulatory approvals, market access, and adoption of this novel combination therapy as a potential new standard for managing CHD.
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