Vir Biotechnology Announces Results of Its Potential Hepatitis B Cure Combination Therapy
The company detailed its preliminary 24-week post–end-of-treatment data for its tobevibart and elebsiran combination, which is being studied for chronic hepatitis B.
Vir Biotechnology, a clinical-stage immunology company, announced results from its MARCH phase 2 trial, which showed the proportion of participants with undetectable hepatitis B surface antigen (HBsAg) at 24 weeks post-end of treatment, was achieved by 17% (3/18) and 21% (3/14) of participants with baseline HBsAg<1,000 IU/mL who were receiving tobevibart and elebsiran without or with PEG-IFNα, respectively. 1
"The MARCH data demonstrate that combinations of tobevibart and elebsiran can achieve and maintain HBsAg loss in a subset of participants with low baseline HBsAg levels,” Vir Biotechnology Chief Medical Officer Mark Eisner, MD, MPH, said in a statement. “These findings provide important insights into the challenges of achieving functional cure in chronic hepatitis B and will inform future development efforts in the field.” 1
The findings were announced during the European Association for the Study of the Liver (EASL) congress in Amsterdam, which were from Part B of the ongoing MARCH study evaluating tobevibart and elebsiran without or with pegylated interferon alpha (PEG-IFNα) in participants with chronic hepatitis B (CHB). 1
Study Parameters
Participants in the trial received tobevibart and elebsiran without or with PEG-IFNα. Tobevibart was administered at 300 mg every 4 weeks; elebsiran, at 200 mg every 4 weeks; and PEG-IFNα, for patients receiving it, at 180 µg weekly. Participants with HBsAg loss (seroclearance) after 48 weeks of treatment who met eligibility criteria discontinued both NRTI (nucleos(t)ide reverse transcriptase inhibitor) as well as tobevibart and elebsiran without or with PEG-IFNα treatment.
The current analysis includes data from participants in the trial who have reached Week 24 post-end of treatment: 51 participants receiving tobevibart and elebsiran without PEG-IFNα and 32 receiving tobevibart and elebsiran with PEG-IFNα. An additional 18 participants receiving tobevibart and elebsiran with PEG-IFNα are currently advancing through the trial.
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 Vir Biotechnology’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 (HDV).
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.
Hepatitis B Burden
CHB is a long-lasting, inflammatory liver disease caused by the hepatitis B virus (HBV).2 The World Health Organization estimates that 254 million people live with CHB, and an estimated 1.1 million yearly deaths are associated with the disease.3 Complications from CHB may include liver cirrhosis, liver failure and liver cancer.4Although CHB can be treated, there is currently no cure.4
