ARO-HBV initial results incredible, up to 4log10 reduction in HBsAG after 3 doses

[Seattledude]

https://finance.yahoo.com/news/arrowhead-presents-aro-hbv-clinical-113000104.html

Arrowhead Pharmaceuticals Inc. (ARWR) will present initial clinical data for ARO-HBV, the company’s third generation subcutaneously administered RNA interference (RNAi) therapeutic being developed as a potentially curative therapy for patients with chronic hepatitis B virus (HBV) infection, at the 18th World Gastroenterologists Summit in Auckland, New Zealand. Data will be presented from the eight patients in the lowest two dose cohorts: 100mg and 200mg. The data demonstrate that three monthly doses of ARO-HBV led to a maximum reduction in circulating HBV surface antigen (HBsAg) of 4.0 log10, with mean reductions of approximately 2.0 log10 on day 85 in the 100 mg cohort and 1.4 log10 on day 71 in the 200mg cohort (currently the last complete data point available). All eight patients achieved greater than 1.0 log10 reductions in circulating HBsAg.

[studyforhope]

The hbsag reductions are more substantial now that the integrated hbsag gene is also included in the interfering action of the drug. But it is still far from the level needed to allow an antibody response to surface.
The reduction results from temporary interfering with messenger RNA processing and is not the result of the elimination of infected or integrated cells. Unless a strong and effective tell response is triggered by these reductions, that will kill those cells, the value will eventually go up again.  
The hbsag reduction achieved by the nap treatments was much stronger and still did not achieve permanent control unless immune activation by interferon or thymusin alpha was added.

[Seattledude]

This is a mid study  presentation, only the 100 and 200 mg results at 90 and 71 days were included. They also have 300 and 40 mg dosed with updates expected at AASLD in Nov. Here is the entire presentation with discussion about combo therapy
http://ir.arrowheadpharma.com/static-files/3443ff1f-71c1-457d-a5a0-0bcd5706ae0f

[Seattledude]

Our experience with two prior compounds, ARC-520 and ARC-521, provides us with confidence that ARO-HBV, which is designed to target all viral transcripts, including those produced by both cccDNA and HBV DNA integrated into host DNA, has the potential to be a backbone therapy in combinations aimed at achieving a functional cure of chronic HBV infection."

[patolino]

That is great news indeed, but just to be clear... is circulating hbsag = hbsag quantity?

[Seattledude]

yes

[Liverpatient]

This is good and encouraging news with so much reduction in hbsag after just three doses. But what I see missing is there is no mention of wether the test groups developed any anti-hbs. Probably the hope is that their own immune system is going to respond to the infection, after a considerable and sustained reduction in hbsag?
Also I've seen in the news that the stocks of Arrowhead have increased by almost 50% in value after the release of this news. Good for those who have invested in those stocks, but for us hbvers, our concern is first and foremost a drug that could help us cure from this menace.

[Seattledude]

No HBsAB yet, but its only 3 months at the lowest dose and as a standalone drug.  (Larger doses will be available for comparison by AASLD in Nov) The chart that was part of the presentation show accelerated HBsAG decline after dose 3 which seems to demonstrate we have not seen the nadir yet. They also have a cohort where they are trialing weekly dose to see if they can drive HBsAG down quicker. Phase 2b will use combinations with new drugs from JNJ and Springbank to multiple protein targets simultaneously. Previous study of 8 dosed patients with inferior ARC-520 had 1 seroconversion and 2 that are likely to seroconvert and that was last drugged 2 years ago. As for me I was mis-diagnosed with HBV 5 years ago which is what brought my attention to a cure. For 3 weeks I thought I had acute HBV so I have a little taste of what the chronic folks have to live with on a daily basis. Hope for a cure for patients is priority

[hepbcurepls]

just read goods news on this. maybe study4hope can give his experience on it.

[Seattledude]

There used to be a lot of folks posting on this site back a few years ago, now it seems very empty. Not sure what happened