Approximately 300 million people worldwide live with chronic Hepatitis B; however, fewer than 1% of them achieve a complete cure. Current medications effectively inhibit viral replication but fail to ensure its total eradication from the organism. Against this backdrop, GSK’s Bepirovirsen offers a pathway toward a “functional cure,” a goal previously considered difficult to attain in medicine.
Data from over 1,800 patients confirm that a course lasting between 24 and 48 weeks induces a “functional cure” in a subset of patients. This implies that the virus is no longer detectable in the blood, and the immune system takes over subsequent control of the infection without the need for ongoing medication.
The persistence of the Hepatitis B virus (HBV) lies in its unique biological cycle. Upon infection, the viral genome enters the nucleus of the liver cell (hepatocyte) and transforms into covalently closed circular DNA (cccDNA). This cccDNA remains as a permanent reservoir within the cell.
Existing antiviral drugs only inhibit viral replication in the blood but cannot access this nuclear reservoir, leading to viral reactivation as soon as medication is discontinued.
The mechanism of action of Bepirovirsen is fundamentally different. It belongs to the class of antisense oligonucleotides, which directly “locate” and bind to viral messenger RNA (mRNA). This binding blocks the synthesis of viral proteins, including the surface antigen (HBsAg). Consequently, the patient’s immune system is able to recognize the virus and destroy the cells where the focus of infection is maintained.
Clinical trials conducted across 29 countries demonstrated that the treatment is particularly effective in patients who initially presented with low viral antigen levels. This group recorded the most successful outcomes. Nevertheless, hepatologist Robert Gish suggests that the primary challenge remains achieving stability of the therapeutic effect. It is necessary to determine whether the body can maintain control over the virus after the cessation of the drug.
Source: Science
