ARC-521

ARC-521 is an investigational RNA interference (RNAi) therapeutic developed for the treatment of chronic hepatitis B virus (HBV) infection. It is designed to silence the production of all HBV gene products by targeting HBV mRNA transcripts derived from both covalently closed circular DNA (cccDNA) and integrated viral DNA. The drug utilizes small interfering RNAs (siRNAs) that engage the cellular RNAi machinery, leading to specific cleavage of HBV RNA transcripts, thereby reducing levels of viral proteins and the RNA template used for viral DNA synthesis. ARC-521 acts upstream of reverse transcription, complementing standard-of-care nucleotide/nucleoside analogs and Arrowhead’s earlier candidate ARC-520. It was intended primarily for patients with lower levels of cccDNA. The goal was to reduce circulating and non-circulating viral proteins and RNAs sufficiently to allow reconstitution of host immune response and achieve HBsAg seroclearance—a functional cure for hepatitis B[2][3][4]. Clinical development included a Phase 1/2 study in healthy volunteers and patients with chronic HBV[2][3]. Development was suspended due to safety concerns related to Arrowhead’s delivery platform[4].