Arrowhead Research Corporation, a targeted therapeutics company, recently filed an application for approval to begin a phase I clinical trial of its RNAi-based therapeutic candidate, ARC-520, against chronic hepatitis B virus infection. Pending approval, Arrowhead intends to proceed with a phase I, randomized, double-blind, placebo-controlled, dose-escalating study to evaluate the safety, tolerability and pharmacokinetics of ARC-520 in normal adult volunteers.

The application was submitted to an ethics committee in compliance with the Clinical Trial Notification process of the Australian Department of Health and Ageing, Therapeutic Goods Administration.

“We are pleased to meet our stated goal of a regulatory submission during the second quarter. This represents an important milestone for Arrowhead as we move our HBV candidate, ARC-520, and the DPC siRNA delivery system towards first-in-man studies,” said Dr Christopher Anzalone, president and chief executive officer.

Hepatitis B virus is the world’s most common serious liver infection, with an estimated 350 million patients worldwide that are chronically infected. HBV can lead to cirrhosis of the liver and is responsible for 80 per cent of primary liver cancers globally. The annual death toll for HBV is estimated as high as one million. Arrowhead’s RNAi-based candidate ARC-520 has the potential to treat chronic hepatitis B virus infection in a fundamentally different manner than current therapies. The goal is to achieve a functional cure, which is an immune clearant state characterized by hepatitis B s-antigen negative serum with or without sero-conversion.

The siRNAs in ARC-520 intervene at the point of DNA transcription, upstream of where nucleotide and nucleoside analogues act, and can deeply knockdown all HBV gene products, including proteins and the viral intermediates necessary to produce viral DNA. In transient and transgenic mouse models of HBV infection, a single co-injection of the DPC delivery vehicle with cholesterol-conjugated siRNA targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins and viral DNA with long duration of effect. Arrowhead is on track to conduct a phase I single ascending dose study in normal volunteers in mid-2013, which the company expects will be followed by a phase IIa study in chronic HBV patients in Hong Kong.

Arrowhead Research Corporation is a clinical stage targeted therapeutics company with development programs in oncology, obesity, and chronic hepatitis B virus infection.