Aa
Replicor approach, A delay Strategy?
Its true that Replicor had not applied for NDA for clinical trial but i would totally disagree with his/er view.
I think they might wish to use their drug for rich people that can afford it and operate as a special drug and will never apply for anything to any regulatory authority.
Surely, what is known about Replicor and REP 9AC out performed any known HBV medication ever, so continue delay of this drug is increasingly suspicious.
I read about Dr. Michael Weitz a Californian emergency room physician and how he overcomed cancer and his decision to enter a Phase I study - the earliest stage of human testing for a new medicine - of crizotinib currently marketed by Pfizer as Xalkori after an unusually swift development process. ( http://news.yahoo.com/insight-cancer-drugs-proving-worth-earlier-testing-064332072--finance.html) .
This is completely opposite to the response received by Dynavax from FDA on HEPLISAV (HEPLISAV is an investigational adult hepatitis B vaccine) See http://investors.dynavax.com/releasedetail.cfm?ReleaseID=742656
It appeared that all odds are against any development in HBV or rather these new developments are being delayed because the big guys are playing catch up.
Make your mind up.
I think they might wish to use their drug for rich people that can afford it and operate as a special drug and will never apply for anything to any regulatory authority.
Surely, what is known about Replicor and REP 9AC out performed any known HBV medication ever, so continue delay of this drug is increasingly suspicious.
I read about Dr. Michael Weitz a Californian emergency room physician and how he overcomed cancer and his decision to enter a Phase I study - the earliest stage of human testing for a new medicine - of crizotinib currently marketed by Pfizer as Xalkori after an unusually swift development process. ( http://news.yahoo.com/insight-cancer-drugs-proving-worth-earlier-testing-064332072--finance.html) .
This is completely opposite to the response received by Dynavax from FDA on HEPLISAV (HEPLISAV is an investigational adult hepatitis B vaccine) See http://investors.dynavax.com/releasedetail.cfm?ReleaseID=742656
It appeared that all odds are against any development in HBV or rather these new developments are being delayed because the big guys are playing catch up.
Make your mind up.
The study using the Rep9ACprime was indeed using either IFN or zadaxin in the final weeks of treatment only, which brought the HBV DNA down to Und and induced an impressive increase in surface antibody levels in all patients but one. I think in Amsterdam they will have a poster that will show the stability of this response after stopping all treatment, which is about 6 month ago.
I ll be in Amsterdam for the conference.
@Studyforhope pls correct if I am wrong about the combo claims regarding Replicor.
@Studyforhope pls correct if I am wrong about the combo claims regarding Replicor.
You have to attend tihe meetings, see they posters, see the curves, the data, the details. Websites are a lousy sorce of info compared with attending the real conferences. And poster content is never printed or shown, you have to be there, take a picture with your camera and with your mind and have real world discussions with other attendents and the presenters of the poster.
To that end they introduced a combo with PegIFN or thymosin alpha, which has already achieved an impressive spike in surface antibody production in almost all treated patients.
Could you tell me the source where you read that they started the combo INF treatement.
Could you tell me the source where you read that they started the combo INF treatement.
It is not that easy with Replicor as it may seem from first glance. Recently I have heard an opinion that the last Replicor study was very disappointing as they were not able to hold the surface antigen conversion after they discontinued therapy.
No doubt Studyforhope points are spot on,however several cases exists where drug company made application for clinical trial or marketing authorization to FDA with forward looking statement/ commitments. I guess part of. Peoples arguments is due to frustration of living with this disease. Lets hope they do the right thing else Myrcludex B has the potential of answering all this questions.
Everything you have stated is really what slows down cure development. This is the problem. Things costing to much. It is societal problem that money and interests of large corporations are placed above common sense and human life saving.
"I think they might wish to use their drug for rich people that can afford it and operate as a special drug and will never apply for anything to any regulatory authority"
You cannot sell any drug, maybe with the exceptions of a few island states in the Carribean, without the regulatory approval. Not to rich people either.
For regulatory approval like in the US and Canada or the EU, you need to perform phase I studies for safety first, then phase 2 studies to show proof of concept in a middle sized study of say 60 to 200 patients, show efficacy is likely, and then you get approval to conduct the large required phase 3 trial that will show absence of major side effects and efficacy in a larger number of carefully defined patients, like eg e antigen positive additionally in a separate trial for e antigen negative patients. After these trials you file for marketing approval, that will be granted based on the weighing of side effects, efficacy and need.
In order to get even approval for a phase I toxicity study, you need to complete preclinical studies, which will typically include animal model toxicity studies of approprate dosing and duration.
The problem with all this is the extreme cost for all these phases. A phase II study let alone a phase 3 is way beyond the capacity of a small startup company like Replicor.
But selling it to a large pharma is not easy. Those need to be reasonable convinced that they are not going to fail in the phase II or III trials,and loose all their investment. Thus even when interested, the risk is high that side effects might show up and the price that they would be willing to offer will strongly depend on their risk assessment. On the other hand, Replicor, convinced that they have a true breakthrough, is not likely to accept a low offer.
Furthermore, a treatment has to be practical for pharma to be interested. While the cost for the substance itself will be drastically lower, once mass production can be used, a weekly infusion in a hospital or clinic is in itself as a procedure very expensive and would shy away insurance carriers or self payers.
For that reason, Replicor rightfully treis to improve on the drug towards a subcutaneous application that can be given to the patient for use at home.
Their trials which have shown the convincing power of suppressing surface antigen particle formation and by subsequent immune activation a dramatic reduction in DNA or virion production, have apparantly proceeded from the first 9AC to the second 9AC' with the hope for lesser side effects and possibly a sc application. Since infusion was still needed for the second generation drug i am sure they are now working on a trial for the third and hopefully final generation that will allow sc application.
Another pressing need is the determination what is required to make the achieved reduction in cccDNA truly permanent. This is not trivial at all and is currently the biggest concern. To that end they introduced a combo with PegIFN or thymosin alpha, which has already achieved an impressive spike in surface antibody production in almost all treated patients.
But it still remains to be seen if this activation is permanent enough to prevent a slow rebound of the virus once all treatment has stopped.
All this takes time and that is unfortunately why it takes years until the problems remaing are resolved and the drug is ready for approval.
You cannot sell any drug, maybe with the exceptions of a few island states in the Carribean, without the regulatory approval. Not to rich people either.
For regulatory approval like in the US and Canada or the EU, you need to perform phase I studies for safety first, then phase 2 studies to show proof of concept in a middle sized study of say 60 to 200 patients, show efficacy is likely, and then you get approval to conduct the large required phase 3 trial that will show absence of major side effects and efficacy in a larger number of carefully defined patients, like eg e antigen positive additionally in a separate trial for e antigen negative patients. After these trials you file for marketing approval, that will be granted based on the weighing of side effects, efficacy and need.
In order to get even approval for a phase I toxicity study, you need to complete preclinical studies, which will typically include animal model toxicity studies of approprate dosing and duration.
The problem with all this is the extreme cost for all these phases. A phase II study let alone a phase 3 is way beyond the capacity of a small startup company like Replicor.
But selling it to a large pharma is not easy. Those need to be reasonable convinced that they are not going to fail in the phase II or III trials,and loose all their investment. Thus even when interested, the risk is high that side effects might show up and the price that they would be willing to offer will strongly depend on their risk assessment. On the other hand, Replicor, convinced that they have a true breakthrough, is not likely to accept a low offer.
Furthermore, a treatment has to be practical for pharma to be interested. While the cost for the substance itself will be drastically lower, once mass production can be used, a weekly infusion in a hospital or clinic is in itself as a procedure very expensive and would shy away insurance carriers or self payers.
For that reason, Replicor rightfully treis to improve on the drug towards a subcutaneous application that can be given to the patient for use at home.
Their trials which have shown the convincing power of suppressing surface antigen particle formation and by subsequent immune activation a dramatic reduction in DNA or virion production, have apparantly proceeded from the first 9AC to the second 9AC' with the hope for lesser side effects and possibly a sc application. Since infusion was still needed for the second generation drug i am sure they are now working on a trial for the third and hopefully final generation that will allow sc application.
Another pressing need is the determination what is required to make the achieved reduction in cccDNA truly permanent. This is not trivial at all and is currently the biggest concern. To that end they introduced a combo with PegIFN or thymosin alpha, which has already achieved an impressive spike in surface antibody production in almost all treated patients.
But it still remains to be seen if this activation is permanent enough to prevent a slow rebound of the virus once all treatment has stopped.
All this takes time and that is unfortunately why it takes years until the problems remaing are resolved and the drug is ready for approval.
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