IONIS-HBVRx

IONIS-HBVRx Report

Name: IONIS-HBVRx Name (English): IONIS-HBVRx DrugBank ID: DB16202 CAS Number: 1403787-62-1 Type: Biotech Background: IONIS-HBVRx, also known as bepirovirsen (GSK3228836), is an investigational antisense oligonucleotide (ASO) being developed for the treatment of chronic hepatitis B (CHB). It was discovered and jointly developed by Ionis Pharmaceuticals and GSK. GSK licensed the program from Ionis in August 2019. IONIS-HBVRx is currently under investigation in several clinical trials, including a long-term follow-up study NCT04544956 (B-Sure) to assess the durability of efficacy in participants who previously received bepirovirsen and achieved a complete or partial response in parent studies like B-Clear (NCT04449029), B-Together (NCT04676724), and B-Fine (NCT04544956).

Mechanism of Action: Bepirovirsen is a 20-mer antisense oligonucleotide that targets all hepatitis B virus (HBV) RNA, including messenger RNA (mRNA) and pregenomic RNA (pgRNA). By binding to these RNA molecules, it promotes their degradation through an RNase H1 mechanism, thus inhibiting the synthesis of viral proteins, including hepatitis B surface antigen (HBsAg), and reducing HBV DNA levels. Additionally, bepirovirsen has been shown to stimulate toll-like receptor 8 (TLR8), which may contribute to the clearance of the virus by the immune system. This triple action – reducing viral replication, suppressing HBsAg, and stimulating the immune system – distinguishes bepirovirsen from current treatments that primarily focus on viral DNA suppression.