Aa
Something has been changed nowadays
Here is a researcher's opinion from the HBV Knockdown Blog about the EASL 2014 meeting.
"Having attended the EASL European Liver Meeting last week and listened to some of the clinical thought-leaders and companies involved in HBV research and treatment, it confirmed the view that there is a GREAT hunger in the field for new approaches to achieve that elusive finite treatment goal for HBV. For this, all differentiated, potentially high-impact new treatment approaches are welcome, RNAi or not. And yes, following the successes in HCV, the industry now views HBV as an opportunity as big as HCV and is shifting its resources accordingly.
There were numerous, not very imaginative studies about trying various permutations of treating HBV with the old, and tired workhorses interferon and NUCs: treat with NUCs, then come in with interferon or vice versa, trying different interferons (alpha or lambda), trying different treatment times…without much, if anything to show for it to change current standard of care.
Where there was progress in HBV was in better understanding the kinetics of this complex disease and in the development of better animal and tissue culture model systems that I expect to greatly facilitate the development of drugs for HBV. For example, following the discovery of NTCP as the viral entry receptor, it is now possible to have HBV replicate in the petri dish. Similarly, there are now mice with not only human livers, but also human immune systems. This is critical for studying immune-based treatment approaches which are viewed as most promising, including HBsAg gene knockdown.
The fact that HBsAg has emerged as a very important biomarker should aid in garnering support for knockdown approaches, although awareness of them is not great yet. This also showed from the reactions to a talk on the ISIS/GSK antisense candidate that I attended. Although multi-log knockdowns were achieved in certain model systems, I did not see great potency at doses that are clinically relevant. For example, what point is a 3 log HBsAg knockdown when you need 200mg/kg oligos in mice (or don't even show the data)? Granted, Arrowhead Research has also advertised knockdown levels with dosages that will not be used in the clinic, but with 2mg/kg they are close to or even better than something quite potent in humans.
With regard to other new treatment approaches besides HBsAg gene knockdown, there is the HBV entry inhibitor Myrcludex which is receiving more widespread attention, although the downside to that approach is that it has no apparent immune angle and would largely work the way that NUCs do…reduce viral load. Finally, there is the idea of inhibiting the PD-1 pathway as discussed in an earlier blog entry, but I’m quite skeptical about the safety of an antibody/small molecule approach here due to potential toxicity arising from the systemic inhibition of this pathway, including autoimmunity. More interesting would be an RNAi Therapeutics approach that targets thepathway specifically in the liver."
"Having attended the EASL European Liver Meeting last week and listened to some of the clinical thought-leaders and companies involved in HBV research and treatment, it confirmed the view that there is a GREAT hunger in the field for new approaches to achieve that elusive finite treatment goal for HBV. For this, all differentiated, potentially high-impact new treatment approaches are welcome, RNAi or not. And yes, following the successes in HCV, the industry now views HBV as an opportunity as big as HCV and is shifting its resources accordingly.
There were numerous, not very imaginative studies about trying various permutations of treating HBV with the old, and tired workhorses interferon and NUCs: treat with NUCs, then come in with interferon or vice versa, trying different interferons (alpha or lambda), trying different treatment times…without much, if anything to show for it to change current standard of care.
Where there was progress in HBV was in better understanding the kinetics of this complex disease and in the development of better animal and tissue culture model systems that I expect to greatly facilitate the development of drugs for HBV. For example, following the discovery of NTCP as the viral entry receptor, it is now possible to have HBV replicate in the petri dish. Similarly, there are now mice with not only human livers, but also human immune systems. This is critical for studying immune-based treatment approaches which are viewed as most promising, including HBsAg gene knockdown.
The fact that HBsAg has emerged as a very important biomarker should aid in garnering support for knockdown approaches, although awareness of them is not great yet. This also showed from the reactions to a talk on the ISIS/GSK antisense candidate that I attended. Although multi-log knockdowns were achieved in certain model systems, I did not see great potency at doses that are clinically relevant. For example, what point is a 3 log HBsAg knockdown when you need 200mg/kg oligos in mice (or don't even show the data)? Granted, Arrowhead Research has also advertised knockdown levels with dosages that will not be used in the clinic, but with 2mg/kg they are close to or even better than something quite potent in humans.
With regard to other new treatment approaches besides HBsAg gene knockdown, there is the HBV entry inhibitor Myrcludex which is receiving more widespread attention, although the downside to that approach is that it has no apparent immune angle and would largely work the way that NUCs do…reduce viral load. Finally, there is the idea of inhibiting the PD-1 pathway as discussed in an earlier blog entry, but I’m quite skeptical about the safety of an antibody/small molecule approach here due to potential toxicity arising from the systemic inhibition of this pathway, including autoimmunity. More interesting would be an RNAi Therapeutics approach that targets thepathway specifically in the liver."
Sorry to ask what sounds like a stupid question but what do you mean "proper"?
But I think in terms of REP9AC' it would only be speculation to say one way or the other if the 8 patients had any bounce back.
But I do agree its a bit disturbing how quiet Replicor are but I'm glad Seattle dude is linked closely with them and he will find out when he speaks with Michel if there was or not. (lets hope for our sake the was no bounce back)
I did speak to a gastro from Bangladesh who is closely linked to the guys involved there & he swears Replicor is the real deal
Studyforhope I know its a bit off topic but I did post a question earlier about vit d 3 whats your opinion please on the ideal amount for HBV people ?
But I think in terms of REP9AC' it would only be speculation to say one way or the other if the 8 patients had any bounce back.
But I do agree its a bit disturbing how quiet Replicor are but I'm glad Seattle dude is linked closely with them and he will find out when he speaks with Michel if there was or not. (lets hope for our sake the was no bounce back)
I did speak to a gastro from Bangladesh who is closely linked to the guys involved there & he swears Replicor is the real deal
Studyforhope I know its a bit off topic but I did post a question earlier about vit d 3 whats your opinion please on the ideal amount for HBV people ?
the surface antigen is in the cuban mix since they hope that the local superantigen effect of the core will stimulate a response against the hbsag as well. it has been shown in much detail in mouse studies by jorg reimann and reinhold schirmbeck that this works very well.
Thank you for the abstract.This is one of the most remarkable achievements with therapeutic vaccines to date. it needs to be used in combo with the NAPs.
multiple doses of arc520 will be a must, as i mentioned, possibly at higher dose levels, side effects permitting. A 90% reduction of hbsag would be way too little to achieve the desired stimulating effect on the adaptive immunity. But it will look good at the meetings and in the press releases. I do sincerely hope they can increase the dose and the frequency of administration.
Why wouldn't they just make a core vaccine as a therapeutic vaccine? Why add the surface Ag? Doesn't everyone infected have enough of that already or am I missing something?
replicor is very silent now regarding the fate of the eight patients. Not a good sign.
the cuban vaccine is a mixed particle vaccine with core particles as the key ingredient. The core particle in itself is a so called superantigen that needs no adjuvant, it is highly immunogenic.
the gs4774 is a string of tcell epitopes engineered to cover all the hbv proteins. The inherent immonogenicity of the carrier particle will need to be proper for presentation and tcell activation in the human patient. One has to wait for the results.
the cuban vaccine is a mixed particle vaccine with core particles as the key ingredient. The core particle in itself is a so called superantigen that needs no adjuvant, it is highly immunogenic.
the gs4774 is a string of tcell epitopes engineered to cover all the hbv proteins. The inherent immonogenicity of the carrier particle will need to be proper for presentation and tcell activation in the human patient. One has to wait for the results.
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