When I spoke Arrow head before and I asked "what function will it serve and the goal of ARC520"? they said
"The theory is that if you can directly reduce s-antigen, you can prompt the body’s adaptive immune system to come back up and clear the virus."
So if this is the case it could be a game changer. I guess all we can do is just see whats in the trials I guess
Thanks for the answer Studyforhope. So in essence ARC520 just another anti viral med like the rest on the market which is disappointing to say the least considering Arrow Heads resources. The only REAL game changer is REP9AC'?
If ARC520 proves itself, even a lifetime of therapy is better than the alternative. I'd be curious to know what sort of timeframe we're looking at for FDA approval/market release. If I understand correctly, there's still a phase 3 to complete. I'd bet it'll be several more years before we see ARC520 on the market. unfortunately, some folks don't have years.
It will depend on how low the hbsag can be driven and other considerations regarding epitope and antigen presentation that could be diminished by reduction of transcription are likely to be relevant. Look at the lengthy discussion in the old thread.
Basically, the most important aspect will be the side effects. If they are minimal, then the dose could be increased and long term treatment is not such a problem. It could be used instead of nucs or to help in cases of resistance.
The interfering RNA itself might be less a problem for side effects, since it should be highly target specific, than the bee venom peptide that is injected independently to break the RNA uptake endosomes membranes for delivery into the cytosol.
Wouldn't the Peg help to clear the DNA at that point?
I am new to this so bear with me please
That is correct. The production of surface antigen and virions will be reduced as long as the interfering RNA remains in the liver cells, which is surprisingly long, but fades after a few weeks by molecular decay.Thus the injections need to be repeated, to keep the effect. A complete elimination is not possible, since the cccDNA is not affected. The hope, that an immune mediated elimination will be triggered by surface antigen reduction, like in the replicor treatment, is unfortunately not realistic, unless repeated. Injections drive the hbsag to much lower levels.
Studyforhope. So technically what your saying is there will be a life time treatment really for ARC520 not a "cure" at all in reality because the patient would have to repeatedly keep taking it. Instead of just antibodies remaining. Is that right?
Great summary! Many thanks.
Do you mind pasting here the link to the long discussion you referred to?
Thank you.
85% knockdown is less than a log, since a log is a tenfold reduction. If you achieve 90% knockdown, then you have a 10 fold reduction or one log. It is just a matter of using simple mathematical terms.
Note than a one log reduction would be way too little to achieve fundamental changes in immunological control. This is artificially induced, not the result of inherent virus restrictive processes of the immune system, that the patient generates of his own powers
.
Maybe upon repeated administration they will be able to go lower.
Note that the functional cure means, than the hepatitis as a liver disease gets better since less antigen is present.Constant therapy will be necessary to maintain this status. But that is quite similar to what the antivirals achieve, a lessening of destructive and profibrotic inflammation. We have discussed the details, pros and cons, of the interfering RNA therapy in a long previous post.