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Anybody know the future of REP 9AC on HBV treatment result recently?
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Anybody know the future of REP 9AC on HBV treatment result recently?

Heard that REP 9AC is a new drug for HBV and it can remove HBsAG at a high ratio. Pls check whether there is new information.
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I only know from www.replicor.com. I pray that they succeed in producing this medicine. The will give hope to millions of people.  On this site they said they successfully brought HBsAg negative to six people.
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Avatar_m_tn
There won't be any progress in at least several years for Replicor97, the Replicor CEO said.
It is far from being available.
However you can try Alinia, maybe another hope. Just ask Stefano.
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Avatar_m_tn
REP 9AC hope it will succeed and will be available soon at a cheap price., Lets hope and pray... about alinia is it available in the Philippines?
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Avatar_m_tn
There won't be any progress in at least several years for Replicor97, the Replicor CEO said

damn it looks like they only work on drugs that dont cure, damn drug makers i read they are still developping useless uncs

let's hope soem researcher finds the right combo and timing among entecavir, tenofovir, interferon, nitazoxanide and simvastatin, to me it looks that drug makers are working to make resistance and gain new clients only

the other hope is myracludex b but they should have started by 2008....
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Thank you all. I am clear on the REP 9AC. Damn, why no people keep researching on this since so many people are anxiously hoping this drug!!

Here is a summery for the latest therapy. Hope you all like it:

http://www.natap.org/2010/HBV/HBVdtherapy.pdf

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Avatar_m_tn
It is because the drug makers want to earn more money from the useless nucls, which can only decrease the viral productions in our serum and leave the real virus in our liver alive. Then all patients have to buy their expensive but limit-effective drugs constantly and permanently to try to control the development of the disease.
If you are the boss, say for example, of one drug maker, and you have developed a very effective drug, which can clear HBV completely in a very short period, what would you do?
To make the most profit, you would probably reduce the performance of the drug and make it to be a long-term therapy. Until the emergence of another effective drug. Then you will be pushed to increase the performance of the current drug.
That is the reality. How pathetic we HBVers are.
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Avatar_m_tn
The conclusion is, the more competition drugs in market, the faster the development of the therapy on HBV will be. Every drug maker has to make its therapy the best, and occupy the market. The profit is unfortunately the only inspiration of the research in drug makers but not the healthy of our patients.

Another possibility is accidentally a HBVer is cured during a therapy for other diseases, and then some mechanism is discovered to deal with HBV. This may happen tomorrow, or 100 years later.
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Avatar_m_tn

i do hope we will be able to find something ourslves from nitazoaxanide and simvastatin, one thing is certain these are more effective on hbsag than all other.
i have seen tenofovir kinetics on hbsag, it is about 0.2-0.5iu/ml lowering per year, almost nothing, we have seen nitazoxanide to be by far more potent on hbsag in hbe negative

cherrynancy has started tenofovir combo.she says she is having a very potent response from tnf since she has been 3 months on nitazoxanide so she is using tnf at 150mg (half dose), unfortunately we have no hbsag quantity tests from her but i am sure we will see good results from 1 year combos of ntz+tenofovir or ntz+etv
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I forwarded the following message from Lei Chou, someone who knows a lot about HBV treatment:
  Lei Chou
  Hepatitis/HIV Project Coordinator
  Treatment Action Group
  611 Broadway, Suite 308
  New York, NY 10012
  Mobile: +1 917.355.3684
  Tel: +1 212.253.7922 x. 215
  Fax: +1 212.253.7923
  Lei.***@****
  Www.treatmentactiongroup.org

  ”We¹ve just published our annual experimental drug pipeline report, my
  chapter on HBV starts on page 70. Sorry the news is not more exciting. You
  can download the report here:
  

You will not find REP9AC and Alinia mentioned in the report. I asked Lei the question:

In your research, did you come across REP 9AC by Replicor  and Alinia from Romark?  REP 9AC had a very small clinical trial involving only  6 patients, but all were reported cured. The Canadian company behind it seems to have no money for any further work. Alinia is FDA approved for another medical condition but has been reported to be effective against HBV and HCV. A few people (in Medhelp) are trying the drug for their HBV condition. The Chief medical officer of Romark is Dr Emmet Keeffer, a well known HBV researcher. Again, there is no ongoing trial involving Alinia. Can you shed any light on why no big pharma seems to interested in these two drugs or  any other?

This is the reply:

I tried to dig up some more information on REP 9AC, to no
avail. Since it's in such an early phase, combined with the small trial done[reported]
in China, I didn't feel there are sufficient data to include it here. I may
be proven wrong, but in general when something sounds too good yet is
lacking financing, I wait to hear more. I contacted Dr. Keeffer two years
ago, who said they were moving forward with Alinia in the states, but have
not heard about any trials to date. I believe they are focusing on the hep C
side. There are other compounds out there that are in similar fates.

I think the difficulty right now is that the two first line drugs on the
market are setting very high bars on efficacy and resistance barrier. For a
new drug to get developed, they'll have to show potential for shorter
duration of treatment, or eradication, not just another "me too" drug. I'm
hopeful that some of the therapeutic vaccines might eventually pan out, but
it's going to be a few years before we can get some definitive answers.


I believe it is time for all of us to organize to urge the Government to fund and initiate a national 5-year project to find a cure for HBV. Chinese scientists, together with colleagues from Taiwan, Hong Kong, Korea, Singapore, Japan, and others can find a cure with the help of governments. If not, we can all donate to start our own research institute.
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Avatar_m_tn

that's to say no money or investors for effective drugs since there is no huge continuous pay back
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Avatar_f_tn
i have seen the articles on the replicor and have browsed the net regarding the nature and mechanism of this drug. it is made by sulfurization of the oligonucleotide adenine and cytosine DNA sequence using sulfating agent like the Beaucage reagent or TEDT.

i was just wondering maybe we can synthesize this modified variant of DNA by finding a sulfurizing agent. for example any drugs which contain sulfur may do the trick. this was just one of my absurd idea on making this med available. are there any biochemist here? one fairly obvious thing that i have observed among the drugs use as antiviral is the sulfur content in their chemical structure like in nitazoxanide.
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Avatar_m_tn
HI,

    WHAT IS THE LATEST NEWS ABOUT THIS MEDICATION,
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Avatar_f_tn
Hi stef what is the latest news about this medication?Is there any development?Thanks
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Avatar_n_tn
Dr.mamun-al-mahtab is the concerned person for REP 9AC
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Avatar_m_tn
WHAT IS THE LEATEST NEWS ABOUT THIS MEDUCATION?? (i.e. NUMBER OF PEOPLU USING THIS MEDICINE? AND % OF CURE?...etc.
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Avatar_m_tn
Please see the following thread for the latest information on REP9AC:

"Entry inhibitors show promise as drugs "
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Avatar_m_tn
Still I can not under stand!!!!  because I am not a doctor..!! please till me what is the latest result about % cure and what is the exepected date for this medicine to be in market??

Thanks a lot....
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Avatar_m_tn
Most of us here are also not doctors or experts. There are various definitions of "cure", so we cannot give you a %. Also, REP9AC had been tested on 14 patients, it is a very small sample. All that I can say, is that REP9AC seems to be more effective in clearing HbsAg than existing drugs.

We don't know when REP9Ac will be available. It will need to go through clinical trials Phase 2 and 3, and to do these trials costs a lot of money and take time.
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Avatar_m_tn
we are all volunteers ..

i know it is so difficult to get some pills of REP9AC ..

what is the effective material they are using?

Stephen .. as i remember in the other thread it was tested for 7 patients, now u said for 14 patients, also i remeber thw all 7 are cured ..

what happened for the new 7 patients?
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Avatar_m_tn
REP9AC is not in a pill form, at the moment. It is given by infusion. The form of REP9Ac is known, but not the exact composition. According to our friend and expert, studyforhope, it is quite complicated to make.

The first human trial for REP9AC had 8 patients. However, only 7 had been followed. A few months ago, another trial was started, this time with REP9AC', an improved formulation of REP9AC, on a new batch of 7 patients. These patients have to be followed longer, but indications are that REPAC' is just as effective.
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ABSTRACT 59
Nucleic acid polymers (REP 9AC / REP
9AC’) elicit sustained immunological
control of chronic HBV infection
M Al-Mahtab1, M Bazinet2, and A Vaillant2
1 Bangabandhu Sheikh Mujib Medical University, Dhaka,
Bangladesh; 2 REPLICor Inc., Montreal, Canada
BACKGROUND: Secreted HBsAg plays a critical role
in suppressing host immunity which permits chronic
maintenance of HBV infection. REP 9AC / REP 9AC’
are nucleic acid-based amphipathic polymers (NAPs)
which inhibit the release of subviral particles from
infected hepatocytes. Previous interim clinical data
has shown that REP 9AC rapidly clears serum HBsAg
in infected patients and allows patients to regain
immunological control over their HBV infection. The
current clinical experience with REP 9AC and a 4th
generation NAP (REP 9AC’) will be presented.
METHODS: All patients were, HBsAg+ with pretreatment
HBV DNA titers between 106 and 1012
copies/ml. REP 9AC or REP 9AC’ was administered by
IV infusion. Safety and virologic response (HBV DNA
[Roche Cobas], HBsAg anti-HBs (Abbott Architect)]
were assessed weekly during treatment.
RESULTS:
(REP 9AC) Treatment achieved > 99.5% reduction of
serum HBsAg in seven out of eight patients. Effective
clearance of HBsAg and development of anti-HBs
were observed as early as 7 days and no later than 32
weeks. All patients responding to REP 9AC achieved
a 3 - 7 log reduction in HBV DNA titers and four of
these seven patients achieved complete control of their
infection with 20-44 weeks of treatment (HBV DNA <
500cpm). Off treatment, three of these four patients
are currently experiencing a sustained immunological
control of their infection (HBV DNA < 500cpm,
and HBsAg  90% reductions in serum HBsAg and 3-7
log reductions in HBV DNA. Mild pro-inflammatory
side effects were consistently observed during drug
administration.
(REP 9AC'). REP 9AC was modified to reduce proinflammatory
activity and improve compound
stability. Early interim data from seven new HBV
patients treated with REP 9AC’ show effective
clearance or substantial HBsAg reductions in all
patients in the first 10 weeks of treatment. Three
of these patients have already experienced a 3-4 log
decline in their HBV DNA. No pro-inflammatory side
effects have been observed to date with REP 9AC’
administration.
CONCLUSIONS: These results demonstrate rapid
effective clearance of serum HBsAg by NAPs which
appears to allow the restoration of host immunity.
In many cases patients experience a durable
immunological control after treatment is stopped.
These results suggest that NAPs may become an
important new tool in the treatment of chronic
hepatitis B.
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Avatar_m_tn
Something went wrong inside this abstract, it is different from the one in the abstract book and the following sentence is incorrect:

Off treatment, three of these four patients
are currently experiencing a sustained immunological
control of their infection (HBV DNA < 500cpm,
and HBsAg  90% reductions in serum HBsAg and 3-7
log reductions in HBV DNA.

IT SHOULD SAY IN THE SECOND PART AFTER "HBSAG": The other four patients are experiencing partial immunological control of their infection with sustained 90% reductions in serum HBsAg and 3-7 log reductions in HBV DNA.

The artificial temporary blocking of surface antigen release unleashes a powerful immune response against previously unattacked HbSAg epitopes ( by Tcell exhaustion  (class I and II!)  by antigen overexposure and other blocking effects) and other portions of the surface antigen.
When this effect is insufficient to reduce the VL to UND - as was the case in 4 out of the seven - we must assume an adaptive response in the viral genome of the critical response elements in the surface antigen protein so as to evade some of the immunological mechanisms now present

or

an inherent incapacity of a particular patient to mount a suffcient strength response reardless of resistance adaptations in the surface antigen response elements.

the first problem could be overcome by antiviral cotreatment to reduce the adaptive/mutational power. Then the HBV system will respond to the desired end -UND and SVR.

The second situation is hopefully rare. Since a substantial reduction in cccDNA during replicor therapy  is nevertheless expected to happen in most of such patients, the maintenance of that blissful state will have to come by external help, that is by continuing antivirals or hopefully with a permanent reinfection blocker  -likely Myrcludex-  that has -again hopefully- less side effects than lifelong antivirals.

Overall the surface antigen blockage should become a powerful new tool , used wisely in optimized combinations to achieve a state of permanently improved health for chronic HBV patients.


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Avatar_m_tn
Many thanks for the correction and explanation. Here is the correct paragraph:
Off treatment, three of these four patients are currently experiencing a sustained immunological control of their infection (HBV DNA < 500cpm, and HBsAg  90% reductions in serum HBsAg and 3-7 log reductions in HBV DNA.

These virus mutations are really a headache. Some research are now indicating that the eAg seroconversion is caused by virus mutations.
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Avatar_m_tn
it seams that REP9AC' had also good result like stand alone treatment, but also like a combo part.

how long in time is REP9AC treatment (or how long it is meant to be) ?
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Avatar_m_tn
REP9AC is currently used for approx. 40 weeks. But since it has only minor side effects it could be used much longer if needed, if the cleanup process of infected cells takes longer.
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Avatar_m_tn
Once more, the correct sentences from REP9AC's abstract:

Off treatment, three of these four patients are currently experiencing a sustained immunological control of their infection (HBV DNA < 500cpm, and HBsAg  90% reductions in serum HBsAg and 3-7 log reductions in HBV DNA.
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Avatar_m_tn
One more time:

Off treatment, three of these four patients are currently experiencing a sustained immunological
control of their infection
(HBV DNA < 500cpm, and HBsAg  90% reductions in serum HBsAg and 3-7 log reductions in HBV DNA
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Avatar_m_tn
Off treatment, three of these four patients are currently experiencing a
sustained immunological control of their infection (HBV DNA less than 500 cpm, and HBsAg  less than 10 IU/mL) for 24, 12 and 12 months respectively. The other four patients are experiencing partial immunological control of their infection with sustained greater than 90% reductions in serum HBsAg and 3-7 log reductions in HBV DNA.
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Avatar_m_tn

Hi,

  what is your suggestion do i proceed for the new protocol Comp(Inteferon+tenover)... or wait for this new medicine(REP9AC')??
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Avatar_m_tn
Hi,

  what is your suggestion do i proceed for the new protocol Comp(Inteferon+tenover)... or wait for this new medicine(REP9AC')?? .

please notice that I am HBe  negative..

  Thanks a lot....
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Avatar_m_tn

we dont know how many years rep9 ac will take to be available so it is definitely better to start sequential treatment by tenofovir and then interferon add on, do not start combo imeediately go for sequential

tenofovir 1-2 years
interferon+tenofovir 2years
if available add alinia too

make also sure to have vit d25oh>60ng/ml
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Avatar_m_tn

- Do you mean that I use tenofovir for maximum 2 years, and if I can not clear the virues then I go to compo?

- what do you mean by vit d25oh>60ng/ml?

-  is this protocol same as in the following clinical traile

  ( http://www.clinicaltrials.gov/ct2/show/NCT00973219?term=hepatitis+b&recr=Open&rank=1http://www.clinicaltrials.gov/ct2/show/NCT00973219?term=hepatitis+b&recr=Open&rank=1 )..

thanks a lot...
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Avatar_m_tn

yes but it is sequential because you need to rescue some immune response towards the virus, so 1-3 years of tdf mono and then interferon add on

not 48weeks, it is 96weeks and more until hbsag gets und


what do you mean by vit d25oh>60ng/ml?
to have your vitamin d serum checked and it has to be higher than 60ng/ml, dont test in other units than ng/ml because confusing and poor sensibility machines are used.vitamin d test is called vitd25oh




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Avatar_m_tn

Hi stef,

Thank you for your help, I have one last question

Is the way of treatment you have mention above published or announced? if yes please give me the link for the study or the clinical trail so that I can give it to my doctor in order to convince..

  Thanks again and again..
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Avatar_m_tn

well if he is a good doctor he must be aware already, it was presented in 2010 conference in berlin and 2011 in san francisco from two different hospitals

here is the thread about it, just look at the hbsag of those who didn t clear yet in 48weeks, it is so low that clearance is certain just  matter of time

http://www.medhelp.org/posts/Hepatitis-B/Add--on-of-peg-interferon-to-a-stable-nucleoside--hbsag-loss-40/show/1616137
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Avatar_m_tn
indirect update:

"  REP 9AC’: A second generation HBsAg release inhibitor with improved tolerability. " - this is the title for a presentation that will came in AASLD in November (no other info available at this moment)
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Avatar_m_tn
Is the program for AASLD 2012 out? Can you provide a link?

I am still waiting for the proceedings of ISVLD held two months ago to be published.
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Avatar_m_tn
http://aasld2012.abstractcentral.com/s1agxt/com.scholarone.s1agxt.s1agxt/S1A.html?&CONFIG_ID=2518&USER_ID=1593989&ROLE_ID=16365&ROLE_TYPE_ID=17&PERSON2ROLE_ID=17804403&WORKFLOW_ID=17&CURRENT_PAGE=BROWSE_THE_PROGRAM&ALLOW_EDIT_INSTRUCTIONS_FL=N&SESSION_ADMIN_PERMISSION_FL=N&REVIEWER_ADMIN_PERMISSION_FL=N&DIRECT_LOGIN_FL=Y&HASH_KEY=yrqbzS8yzVEezNSZD0XqU9xbfCw&STUB_ROLE_ID=0&TIME=1346080075691&SOURCE_URL=http://aasld2012.abstractcentral.com


or go to http://www.aasld.org/lm2012/2012/attendees/Pages/ItineraryPlanner.aspx and click on Itinerary Planner and you ca see the program (maybe not the final one but the latest one)
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Avatar_m_tn
I was not keep an eye on ISVLD. do you have any link to this ?
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Avatar_m_tn
Thanks for the AASLD links - I remember the itinerary way to see the program. I have a quick look, very exciting program, REP9Ac, Myrcludex, GS-9620, PegINTF + ETV/TDF are all there.

ISVLD proceedings are supposed to be published in Journal of Viral Hepatitis.
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Avatar_m_tn
They need to give these drugs to us now! We have to ask for it.
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Avatar_m_tn
REPLICor presents clinical efficacy and toxicology results in patients with chronic hepatitis B with short term exposure to immunotherapy after REP 9AC’ induced clearance of serum HBsAg.

14 May 2013, Boston, U.S.A.

Montreal, Quebec – Tuesday , May 14th, 2013 – REPLICor has previously undertaken a proof of concept trial to examine the efficacy of REP 9AC monotherapy in patients with chronic HBV infection.  A second proof of concept trial is currently underway in patients with chronic hepatitis B (HBV) undergoing treatment with REP 9AC’ in combination with Zadaxin™ or Pegasys™.

Efficacy and toxicology results in REPLICor’s proof of concept trials from monotherapy exposure to REP 9AC or REP 9AC’ were disclosed on Tuesday May 14th, 2013 at the 15th annual TIDES meeting held in Boston, U.S.A.

Both REP 9AC and REP 9AC’ were shown to rapidly and effectively remove HBsAg from the blood of patients with HBV infection.  While REP 9AC monotherapy led to the establishment of control of infection off treatment in 2/7 patients, the addition of immunotherapy (either Pegasys™ or Zadaxin™) after REP 9AC’ mediated HBsAg clearance led to profound increases in immune function in all patients and in 8 out of 9 patients, control their viral infection has been maintained for 12 – 24 weeks after all treatment is stopped.

Toxicology results from weekly monotherapy exposure to REP 9AC or REP 9AC’ in many cases > 1 year resulted in no observable drug related effects on liver and kidney function or in lipid or hematological function.  Major reported symptoms were shown to be related to the development of mineral deficiency likely due to the mineral chelation properties of these compounds and were controlled or prevented with proper mineral supplementation during treatment.

These results show the well tolerated nature of long term treatment with the nucleic acid polymer compounds REP 9AC and REP 9AC’ and further show the promise of achieving well tolerated control of HBV infection with combination treatments using these agents.

For the 15th annual TIDES meeting:
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Avatar_m_tn

Title Short Term Immunotherapy Following REP 9AC'-Induced HBsAg Seroclearance, Induces Durable Immunological Control of Chronic HBV Infection

Speaker: Andrew A. Vaillant

Author: Mamun Al- Mahtab1, Michel Bazinet2, Andrew Vaillant2
Affiliation: 1Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, 2REPLICor Inc., Montreal, QC, Canada

Session: Oral Session: Late Breakers

Date: Saturday - June 08, 2013 16:50-17:00

Location: Hall 9

Background: REP 9AC' is a nucleic acid-based polymer (NAP) that clears serum HBsAg by blocking HBV subviral particle formation and release. The effect of add-on immunotherapy after HBsAg clearance in chronically infected patients receiving REP 9AC' was examined.

Methods: Add-on immunotherapy to existing REP 9AC' therapy was initiated in patients who had cleared their serum HBsAg but with persistent serum HBV DNA. Immmunotherapy consisted of thymosin a1 (Zadaxin™) or pegylated interferon a-2a (Pegasys™). Virologic responses were monitored by measuring serum HBV DNA (Roche Cobas™), serum HBsAg and serum anti-HBs (Abbott Architect™).

Results: REP 9AC'-induced HBsAg seroclearance is accompanied by the appearance of anti-HBs and reductions in serum HBV DNA. However, the continued production of anti-HBs in most patients never exceeded 50 mIU/ml and serum HBV DNA levels in most patients persisted in the range of 1000-3000 cpm. Addition of either Zadaxin™ or Pegasys™ to REP 9AC' therapy resulted in dramatic increases in anti-HBs titers with as little as 5 weeks of immunotherapy to levels comparable to or greater than titers observed in healthy patients with a strong vaccine response. Combination treatment was halted in 8 patients after 12-27 weeks of immunotherapy. In these patients, anti-HBs levels are persistently between 400 and 1000 mIU (5 of 8 patients) 12-24 weeks off treatment. HBV DNA levels are also persistently below 116 CPM (Cobas™ LLOQ) in 6 of 8 patients and > 250 CPM in the other two patients.
Conclusions: REP 9AC'-induced HBsAg seroclearance appears to potentiate the immunostimulatory effects of either Zadaxin™ or Pegasys ™ in all patients. Short term exposure to immunotherapy in the absence of HBsAg may induce permanent immunological control of HBV infection in most patients.
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Avatar_m_tn
exciting news!!!
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Avatar_m_tn
cool development. this thread is a bit long now, perhaps the news needs a new one.  
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Avatar_m_tn
Exciting news!!!! we need to demand to have this drug now at any cost
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Avatar_m_tn
that is what I am telling you guys all the time here..

We need to stop talking about NUCs, and ask for this therapy..

I am mean why nobody from Replicor comes here? We wrote them many times! This medicine works with interferon so why not use it..

Everybody write them here http://www.replicor.com/debut_anglais2.htm and demand answers. We need this drug now..
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Avatar_m_tn
this is great news that there are no side effects
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Avatar_m_tn
is it really true and coming to hit the market?when any guess.
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Avatar_m_tn
Dont think of it as a market. Because they think of it as a market we still dont have cure.

Healthcare for profit is criminal. A reflection of an amoral society we all live in.
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