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ARO-HBV progressing in phase 1/2 trial, active against cccDNA and integrated DNA

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
DNA.

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.
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Avatar universal
Good information but the trial is going so slow. Just I2 phase!
Helpful - 0
2 Comments
ARC 520 was abandoned a few years ago but they have kept track of the 8 people who were dosed and 3 may seroclear. ARO-HBV is the 2nd generation that targets both cccDNA (Like ARC-520) and integrated DNA (ARC-520 had no activity here) Real data is expected by the liver conference in Nov, but the safety profile and activity observed thus far look promising. If all goes as planned (Which usually doesn't happen), the drug could be ready for commercial use by late 2020.
I should clarify by saying that 1 of the 8 people has already serocleared and 2 others are looking as if they will soon. Its important to note that no one has been dosed with ARC 520 in years but still seeing benefit. ARO_HBV is better targeted in so many ways to ARC-520, I am very encouraged by these recent developments and I have been following HBV drug development since I was mis-diagnosed with HBV in 2013. Good luck to all who are effected by HBV, I hope this is finally the answer many have been looking for
Avatar universal
Ya certainly u,ve posted a very vivid post. Things like this is the biggest anticipation of hbvers and the big question when will "it" come. It's nice to know u r not affected with hbv but still showing this level of interest. Applauding! Good info about aro.
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