Vir Biotechnology Shares Positive Chronic Hepatitis Delta Trial Results, Launches Phase 3 Program

Vir Biotechnology, Inc. (NASDAQ:VIR) has announced promising outcomes from the SOLSTICE Phase 2 clinical trial, which evaluated the combination of tobevibart and elebsiran in individuals with chronic hepatitis delta (CHD). This trial tested the efficacy of the combination therapy, which includes an investigational human monoclonal antibody and siRNA, administered monthly. The results showed a 100% virologic response and rapid suppression of hepatitis delta virus (HDV) RNA.

The trial demonstrated that 41% of participants achieved HDV RNA levels below the lower limit of quantification by Week 24, which increased to 64% by Week 36. In a cohort that reached Week 60, 80% of participants achieved undetectable HDV RNA levels. These significant findings were presented at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting in San Diego, CA.

Given the encouraging results, Vir Biotechnology plans to initiate the Phase 3 ECLIPSE program in early 2025. This program aims to further assess the combination of tobevibart and elebsiran for CHD treatment.

CHD is a severe form of chronic viral hepatitis caused by HDV, known for its rapid progression to cirrhosis and liver failure within an average of five years. Currently, no approved treatment exists in the United States. The goal of the therapy is to eliminate the virus from the body, and combination therapy has shown potential by targeting various stages of the viral lifecycle.

Clinical trial participants were randomly assigned to receive either tobevibart 300 mg every two weeks or a combination of tobevibart 300 mg and elebsiran 200 mg every four weeks. Participants from previous monotherapy cohorts could also transition to the combination therapy. Virologic suppression rates were assessed at multiple intervals, with promising results sustained up to 60 weeks.

The data revealed that 100% of participants in the combination therapy arms experienced a significant reduction in HDV RNA levels by Week 24, with this rate maintained at subsequent time points. Furthermore, the combination therapy resulted in significant reductions in hepatitis B surface antigen (HBsAg) values, indicating effective suppression of critical biologic mechanisms required for HDV replication.

Alanine aminotransferase (ALT) normalization was observed in nearly half of the participants by Week 24, with sustained results at Week 36. The combination therapy achieved both virologic suppression and ALT normalization in a significant number of participants.

The safety profile of the combination therapy was consistent with previous studies, with most treatment-emergent adverse events being mild or moderate. No severe adverse events related to the treatment were reported, and no participants discontinued the study due to safety concerns.

Marianne De Backer, CEO of Vir Biotechnology, emphasized the urgent need for effective treatments for hepatitis delta, especially in the U.S. where approved options are lacking. She expressed confidence in the transformative potential of their regimen and highlighted plans to advance the Phase 3 ECLIPSE program based on the strong SOLSTICE data.

The ECLIPSE program will include three randomized, controlled trials to compare the combination therapy with deferred treatment or bulevirtide. These trials aim to generate the necessary efficacy and safety data for regulatory submissions globally. ECLIPSE 1 will focus on comparing the combination therapy with deferred treatment in regions where bulevirtide is not available. ECLIPSE 2 will evaluate the switch to the combination therapy in individuals who have not achieved viral suppression with bulevirtide. ECLIPSE 3 will compare the combination therapy head-to-head with bulevirtide in bulevirtide-naïve patients.

The U.S. FDA has granted fast track designation for the combination of tobevibart and elebsiran for CHD treatment, aiming to expedite the development and review process for this promising therapy. Additionally, the European Medicines Agency has issued a positive opinion on the orphan drug designation for the combination therapy, supporting its development for life-threatening conditions with significant unmet needs.

In conclusion, the Phase 2 SOLSTICE trial results support the potential of the tobevibart and elebsiran combination therapy to significantly improve outcomes for patients with chronic hepatitis delta. The upcoming Phase 3 ECLIPSE program will further evaluate this promising therapy, with the aim of providing a much-needed treatment option for this severe liver disease.