SATURDAY, OCTOBER 1, 2016

Arrowhead reduces 90 percent of hepatitis B antigens in chimpanzee study

Arrowhead Research Corporation, a Pasadena, California-based targeted therapeutics company, recently announced a preclinical chimpanzee study that demonstrated the success of its RNA interference-based hepatitis B virus therapeutic.

ARC-520 is a hepatitis B antiviral candidate that works using a gene silencing RNAi mechanism. The study, which was conducted at the Texas Biomedical Research Institute, found that a low dose of ARC-520 induced deep and rapid reductions in hepatitis B viral particles and key viral antigens. The well-tolerated, low dose of ARC-520 resulted in a 95 percent reduction of circulating viral DNA and approximately 90 percent reductions in hepatitis e-antigen (HBeAg) and s-antigen (HBsAg).

"This is the first time I have tested an siRNA therapy that was efficiently delivered to the liver and suppressed HBV infection including serum levels of HBsAg, a marker that is not suppressed effectively using current therapies," Robert Lanford, a scientist with the Texas Biomedical Research Institute, said. "This was a proof-of-concept study with a novel approach for curing HBV infection and this therapy provided highly promising results in a very short trial."

The data support previous findings in rodent models and could be predictive of a therapeutic dose range that will be determined in upcoming clinical trials expected to start in mid-2013.

"Treating this animal represented a very difficult challenge," Chris Anzalone, the president and CEO of Arrowhead, said. "It was the first large primate to be treated with ARC-520, and its viral and s-antigen loads were many orders of magnitude higher than what we expect to see in humans. Even with this high bar, we showed that a low dose was effective and extremely well tolerated. There is currently no way to reliably knock down key HBV antigens, thought to be critical to achieving a functional cure of the disease. Our data in multiple rodent models and now in a chimpanzee with chronic HBV infection suggest that ARC-520 may be able to provide this. We believe this is very important and positions us well for our planned clinical trials this year."

Arrowhead hosted an event on Monday to discuss ARC-520 in more detail.

Hepatitis B has been a chronic infection for more than 30 years and has endured despite prior therapy with anti-viral drugs and exposure to therapeutic vaccines.