Arrowhead Research Corporation (NASDAQ: ARWR), a targeted therapeutics company, today announced the publication of data demonstrating multi-log reductions in hepatitis B viral DNA and proteins lasting over 30 days after a single injection in animal models. This suggests that Arrowhead’s RNAi-based candidate ARC-520 has the potential to treat chronic hepatitis B virus infection in a fundamentally different manner, with the goal of achieving a functional cure. The paper, entitled “Hepatocyte-targeted RNAi therapeutics for the treatment of chronic hepatitis B virus infection,” by Wooddell et al, was published online ahead of print in the journal Molecular Therapy (doi:10.1038/mt.2013.31).
In the publication, Arrowhead scientists describe the use of a novel Dynamic PolyConjugate (DPC) technology to deliver small interfering RNAs (siRNAs) designed against the hepatitis B virus (HBV). This DPC technology incorporates a biodegradable peptide composed of naturally occurring amino acids and a liver-targeted molecule that is co-injected with a cholesterol-conjugated siRNA (chol-siRNA). In proof-of-concept studies, utilization of this DPC to deliver chol-siRNA targeting Factor 7 to non-human primates results in >99% knockdown of target gene expression and >80% knockdown for over one month after a single injection. Multi-dose studies in mice showed no diminution of knockdown activity or toxicity upon repeated injection at therapeutic doses. In transient and transgenic mouse models of HBV infection, a single co-injection of DPC with chol-siRNA targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins and viral DNA with long duration of effect.
"This publication is important because it speaks to a specific product and a broader platform,” said Dr. Christopher Anzalone, President and Chief Executive Officer. “These data suggest that ARC-520 could be a powerful therapy for chronic HBV infection, a disease with 350 million infected people worldwide and no cure. We are on schedule to file with regulatory authorities next quarter to begin first-in-human studies. During phase 1 we will be able to measure the drug’s ability to knock down production of new infectious virus as well as viral proteins, including s-antigen, e-antigen, and the core protein that forms the capsid. The ability to substantially knock down these viral proteins is what is unique about ARC-520 and what many in the field believe will be necessary to revive the host immune response and potentially provide a functional cure, which no other current therapy can reliably do. More broadly, this paper reports on a delivery system capable of extremely efficient gene silencing that can be used for a variety disease targets.”