ARC-520 + entecavir

ARC-520 + entecavir is a combination therapy for **chronic hepatitis B virus (HBV) infection**. ARC-520 is an RNA interference (RNAi) therapeutic designed to reduce the expression of HBV messenger RNAs, leading to decreased production of hepatitis B surface antigen (HBsAg) and other viral proteins. Entecavir is a nucleoside analogue reverse-transcriptase inhibitor that inhibits hepatitis B virus DNA polymerase, suppressing viral replication. The combination aims to achieve synergistic antiviral effects: ARC-520 reduces viral antigens at the mRNA level, while entecavir continuously suppresses viral DNA production. Clinical trials have investigated this combination in HBeAg-positive and HBeAg-negative patients, both treatment-naive and nucleos(t)ide-experienced, typically using intravenous ARC-520 and oral entecavir. ARC-520 was developed by Arrowhead and acts upstream of where nucleoside analogues like entecavir act, targeting the virus by reducing protein expression and release, and therefore enabling potentially deeper viral suppression and immune reconstitution leading to a possible functional cure.