First Patient Enrolled for Combination Therapy in Phase 3 Trial for Chronic Hepatitis D

Today, Vir Biotechnology announced the enrollment of the first patient in its ECLIPSE 2 phase 3 trial for chronic hepatitis delta (CHD).¹ “Patients living with chronic hepatitis delta, a known cause of liver cancer, are waiting for effective options to change the course of their disease,” Vir Biotechnology CEO Marianne De Backer, MSc, PhD, MBA, said in a statement. “We are excited about the rapid progress of our ECLIPSE program, which demonstrates our unwavering commitment to deliver a highly effective treatment for people living with chronic hepatitis delta.”¹

There are currently no approved treatments in the US for HDV, and options are limited in the European Union and globally.¹

Study Parameters

ECLIPSE 2 will evaluate the efficacy and safety of switching to tobevibart and elebsiran in people with CHD who have not achieved viral suppression with bulevirtide therapy. ECLIPSE 1 and 2 are designed to provide the registrational efficacy and safety data needed for potential submission to global regulatory agencies. ECLIPSE 3 is a Phase 2b head-to-head trial to evaluate tobevibart and elebsiran compared with bulevirtide in bulevirtide-naïve patients, and it is designed to provide important supportive data to help establish access and reimbursement in key markets.¹

ECLIPSE 2 plans to enroll participants in regions where bulevirtide is approved for the treatment of CHD. Participants who fail to achieve virologic suppression (defined as failure to achieve HDV RNA TND) after a minimum 24 weeks of bulevirtide treatment will be randomized 2:1 to switch to the combination of tobevibart and elebsiran or continue receiving bulevirtide. The primary endpoint in ECLIPSE 2 measures HDV RNA at the lower limit of quantification target not detected, HDV RNA TND (defined as HDV RNA = 0 IU/mL), at Week 24.¹

About the Agents

Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen (HBsAg). It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart was identified using the company’s proprietary monoclonal antibody discovery platform. The Fc domain has been engineered to increase immune engagement and clearance of HBsAg immune complexes and incorporates Xencor’s Xtend technology to extend half-life. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis delta.

Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) discovered by Alnylam Pharmaceuticals. It is designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicate that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis delta.¹

Learn more: Findings From Screening Study for Hepatitis B and Hepatitis D Demonstrate Need for Follow-Up Testing

Hepatitis D Burden

Chronic HDV infection is the most severe form of viral hepatitis, with both a poor prognosis and high rates of mortality. And for those patients who have HDV and compensated cirrhosis with clinically significant portal hypertension (CSPH), they have very limited treatment options. Traditionally the only therapy available has been the off-label use of pegylated-interferon-a (PegIFNa), which has demonstrated limited therapeutic responses and an unfavorable safety profile.

Wranke et al showed that having HDV leads to a faster progression to the aforementioned conditions and other liver-related end points.²

References
1.Vir Biotechnology Initiates Second Pivotal Trial in Its Global ECLIPSE Registrational Program for Chronic Hepatitis Delta. Vir Biotechnology. July 31, 2025. Accessed July 31, 2025.
https://investors.vir.bio/news/news-details/2025/Vir-Biotechnology-Initiates-Second-Pivotal-Trial-in-Its-Global-ECLIPSE-Registrational-Program-for-Chronic-Hepatitis-Delta/default.aspx
2. Wranke A, Heidrich B, Deterding K, et al. Clinical long-term outcome of hepatitis D compared to hepatitis B monoinfection. Hepatol Int. 2023;17(6):1359-1367. doi:10.1007/s12072-023-10575-0