Dive Brief:
- Data from a Phase 2 open-label study of ARC-520 showed a sustained host response after finishing treatment. Arrowhead Pharmaceuticals Inc. presented the data on the discontinued hepatitis B candidate in order to help show supportive evidence for its RNA interference approach.
- The study, presented at the 22nd biennial HEP DART meeting held in Hawaii, found two of three HBV e-antigen-positive patients and two of five HBV e-antigen-negative patients showed continued reductions in key HBV markers at seven months after the last dose. It also showed an increase in circulation of liver enzyme alanine aminotransferase (ALT), which indicates a host response.
- In a separate, preclinical study of its now lead candidate ARO-HBV, levels of HBV DNA, HBsAg and HBeAg dropped below levels of quantitation. A clinical trial application filing for that candidate is planned by the second quarter of 2018.
Dive Insight:
Access to near curative therapeutics has revolutionized the treatment of chronic hepatitis C, potentially changing the life of thousands of people. However, there is still no functional cure for chronic hepatitis B infection. Around 1.2 million people across the U.S. are infected with hepatitis B, and up to a quarter of these could develop liver damage or cirrhosis, liver failure or liver cancer.
Arrowhead's ARC-520 showed promising early results in a clinical trial in 2015. However, in 2016, the Food and Drug Administration placed a clinical hold on the project after questioning deaths in an animal toxicology study. Arrowhead halted development of ARC-520 and ARC-521, both targeting HBV and another clinical program.
The company has now shifted its focus to ARO-HBV, a new-generation RNAi drug designed to silence the production of all HBV gene products. The idea behind this is that the patient's immune system can then reconstitute itself and generate a host response against the virus.
"These data represent the first clinical evidence that an RNAi-based approach can lead to the type of favorable sustained host response that we have always believed is possible," said Bruce Given, chief operating officer and head of R&D for Arrowhead, in a Dec. 6 statement.