ARC-520 / Arrowhead - LARVOL DELTA

Long-term hepatitis B surface antigen response after finite treatment of ARC-520 or JNJ-3989. (PubMed, Gut) - "Short-duration siRNA treatment suppressed HBsAg expression with a prolonged effect for up to 6 years in some participants."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Long-term hepatitis B surface antigen response after finite treatment with siRNAs ARC-520 or JNJ-3989 (EASL-ILC 2024) - P1/2, P2 | "siRNA treatment suppressed HBsAg expression with a prolonged effect for up to 6 years. The siRNA-100 score consisting of baseline qHBsAg and log reduction at nadir may be indicative of HBsAg level <100 IU/mL at LFU."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

RNA Interference Therapy for Chronic Hepatitis B Predicts the Importance of Addressing Viral Integration When Developing Novel Cure Strategies. (PubMed, Viruses) - "Early clinical testing with the first of these agents in the clinic, ARC-520, demonstrated that rapid and deep reductions in viral proteins, RNA and DNA could be produced with this approach, but also the surprising insight that HBsAg production from incomplete HBV DNA integrated into the host genome appears to play a heretofore unappreciated and important role in maintaining circulating HBsAg, thought to play a fundamental role in preventing host clearance of the virus. Thus, accounting for viral DNA integration in novel HBV treatment approaches may prove to be essential to achieving successful finite therapies of this difficult to treat chronic infection."

Journal • Review • Hepatitis B • Hepatology • Infectious Disease

Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment. (PubMed, Gut) - P2 | "MD ARC-520 therapy achieved sustained and profound reductions of viral antigens and HBV RNA. HBsAg seroclearance was achievable."

Clinical • Journal • Hepatitis B • Hepatology • Immunology • Infectious Disease

Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection. (PubMed, Sci Rep) - "The observed continuous HBV DNA decline is entecavir mediated, the strong but transient HBsAg and HBeAg decays are ARC-520 mediated. The modeling framework may help assess ongoing RNAi drug development for hepatitis B virus infection."

Journal • Hepatitis B • Hepatology • Infectious Disease

A Multi-dose Study of ARC-520 in Patients With Hepatitis B 'e' Antigen (HBeAg) Negative, Chronic HBV Infection (clinicaltrials.gov) - P2; N=58; Terminated; Sponsor: Arrowhead Pharmaceuticals; Recruiting ➔ Terminated

Trial termination • Biosimilar • Immunology

A phase 1 study to evaluate safety and tolerability of escalating single doses of the hepatitis B virus RNA interference drug ARC- 521 in a healthy volunteer population (ILC 2017) - "Background and Aims: Safety and antiviral activity of single, ascending doses of ARC-520, a RNA interference therapeutic for chronic Hepatitis B virus (HBV) that targets only cccDNA-derived mRNA have been reported previously... Single doses of ARC-521 appear to be safe and well tolerated up to a dose of 6 mg/kg in a healthy volunteer population. A multi-dose study of ARC-521 in HBV patients is ongoing."

Clinical • P1 data • Biosimilar • Hepatitis C Virus • Immunology • Oncology

RNA Interference Therapy with ARC-520 Results in Prolonged HBsAg Response in Patients with Chronic Hepatitis B Infection. (PubMed, Hepatology) - "ARC-520 was well tolerated, with only two SAEs of pyrexia possibly related to study drug observed. In conclusion, ARC-520 was active in both E-neg and E-pos, NUC experienced HBV patients, but absolute HBsAg reductions were moderate, possibly due to expression of HBsAg from integrated HBV DNA, indicating the need for RNAi therapeutics that can target viral transcripts regardless of origin."

Clinical • Journal