Over 90% Viral Knockdown in HBV-Infected Chimpanzee with DPC Delivery

Arrowhead Research today provided a little appetizer ahead of its analyst event for ARC520, its candidate for the treatment of chronic hepatitis B (profiled here).  The press release stated that with a single injection of the DPC formulation, serum HBV DNA levels in a chronically infected chimpanzee were reduced by ‘greater than 90%’.  This suggests that the knockdown of the direct target, HBV mRNAs (incl. for the critical HBsAg), was on the same order.  Although the knockdown number here refers to a replicating virus, they are consistent with the high potency of DPC seen in other monkey studies.

The obvious limitation of the present study is that only one animal was treated.  Infected chimpanzee studies are almost impossible to conduct these days, and I am curious how the company got access to the animal in the first place.  The study is being conducted at the Texas Biomedical Research Institute and was led by Robert Lanford.  Dr. Lanford is well known for his chimpanzee work for viral infections, including proof-of-concept for miR-122 inhibition for the treatment ofHepatitis C (Santaris program) and, more recently, chronic HBV studies for Gilead’sTLR7-agonist GS-9620.

Nevertheless, as the animal served as its own control and HBV DNA levels do not fluctuate much from day-to-day, obtaining a credible >90% knockdown without being able to rely on a proper dose-finding study, is remarkable and suggests that more potent results would have been obtained with higher and more frequent dosing.

More about the clinical dosing plans and additional data on the chimpanzee, esp. the HBsAg knockdown data that are so critical to the immune reconstitution hypothesis central to ARC520 (read here for why), should be forthcoming at the March 25 analyst meeting.  Mark your calendars.