2013年11月11日讯 /生物谷BIOON/ --致力于RNA疗法的Arrowead Research公司最近公布一组数字支持其开发的乙肝RNAi疗法ARC-520。这种疗法通过将RNA输送至细胞核而引起免疫反应从而治疗乙肝。在以往，在体内安全高效输送RNA是困扰科学家的难题之一，但最近这一问题取得突破，Arrowhead利用公司的Dynamic polyconjugate输送系统能够准确输送RNA至预定目标。目前ARC-520正处于一期研究，公司正在进行其二期研究的准备工作。（生物谷Bioon.com）
RNA delivery specialist Arrowead Research ($ARWR) heralded new data supporting its genetic treatment for hepatitis B, which makes use of the company's polymer-based method for effectively getting RNAi to the nucleus. And its immunological response offers what could be a "functional cure" for the disease.
Pasadena, CA-based Arrowhead's hepatitis B candidate ARC-520 showed in a primate study to substantially reduce the viral DNA, as well as antigens associated with the disease, for over two months. And importantly, an "immunological flare" results from an increase in serum alanine transaminase after four weeks, which the company said could lead to antigen conversion and a "functional cure," as presented this week at the American Association for the Study of Liver Diseases' annual meeting.
This is a major step for hepatitis B in particular and for RNAi capability in general. The delivery of genetic drugs has been a major hurdle in the past, but recent clinical and financing successes for Arrowhead and other companies such as Alnylam ($ALNY) and Arcturus have demonstrated a turning point. Arrowhead's Dynamic Polyconjugate delivery vehicle uses a "masking" and "unmasking" process that allows RNA to enter the cell unharmed and then "escape" once it reaches the target.
"This study would have been important if ARC-520 just demonstrated safe and effective HBsAG (antigen) reduction because this is thought to be a necessary step in achieving a functional cure," said study author Robert Lanford. "What is really exciting about these data, however, is that we appear to have seen immune de-repression, the next step toward HBsAg seroconversion and functional cure. The timing of the ALT rise and associated increases in key chemokine/cytokine mRNAs suggest that they were related to the therapy-induced reduction in circulating HBsAg and represented an immunological event."
This month, Arrowhead's CEO Christopher Anzalone spoke to FierceDrugDelivery about ARC-520's Phase I enrollment and its upcoming Phase IIa multinational study. The company, which closed a $60 million private offering on Oct. 11, is building up its preclinical pipeline, as well as two additional RNAi clinical candidates with the cash.
"This is an important addition to our data set and a milestone for the development plan of ARC-520," Anzalone said in a statement this week.