From Arrowhead CC yesterday: We have not presented any data from the ARO-HBV study, but to date 63 subjects have received at least 1 dose. 30 healthy volunteers and 33 patients with chronic
HBV infection have received a total of 104 injections of ARO-HBV. It has been
generally well tolerated at all dose levels studied, with no serious or severe adverse
events. In addition, early data in patients indicate that the drug is clearly active.
Importantly, we believe these data suggest that ARO-HBV is active in silencing s-antigen
production from both HBV cccDNA and viral DNA that has integrated into host DNA. This would represent a large step forward from our first generation candidate, ARC-520, which did not address s-antigen transcripts from integrated
During the last quarter we presented some clinical data on our prior generation
HBV compound, ARC-520, at the EASL International Liver Congress. These data
included follow up for 8 patients that received up to 9 monthly doses of 4 mg/kg
ARC-520 with daily entecavir in the Heparc-2001 multi-dose extension study. As
I mentioned, a key limitation of this candidate was that it only targeted HBV
cccDNA and did not address s-antigen transcribed from integrated DNA. We
discovered that this can be a substantial source, and sometimes the primary source,
of circulating s-antigen. Even so, half of these patients experienced a sustained
host response, where it appears that ARC-520 triggered something that enabled the
body to fight the virus. This was the intended mode of action for ARC-520 and is
the intended mode of action for ARO-HBV. It has been our theory that if an RNAi
therapeutic can reduce viral antigens sufficiently and decrease immunosuppressive
forces, the immune system may “re-awaken” to control the virus and enable a
durable functional cure. One e-antigen negative patient that received ARC-520
treatment, while remaining on entecavir, serocleared for all measurable viral
markers including s-antigen, core-related antigen, HBV RNA, and HBV DNA.
We believe this will represent a functional cure. Two additional patients that
experienced sustained host responses but had not yet serocleared, appeared poised
to potentially seroclear if the trends in the decrease of viral markers continues.
We, and many key opinion leaders in HBV, see these data as the first proof-ofconcept
that an RNAi compound can potentially lead to an awakening of the
immune system in HBV patients and eventual functional cure.