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Newest Repac Abstract

HBsAg and HDV RNA reduction with REP 2139-Ca and peg-INF alpha 2a in chronic HBV/HDV infection.

Nucleic acid polymers (NAPs) inhibit the release of HBsAg and the NAP REP 2139 can efficiently clear HBsAg from the blood of patients with HBV mono-infection. REP 2139-Ca therapy combined with pegylated interferon alpha-2a is being evaluated in Caucasian patients with HBV/HDV co-infection (NCT02233075).
Patients received REP 2139-Ca once weekly for 15 weeks (500 mg) by 2 h IV infusion, followed by combined therapy for 15 weeks with pegylated interferon alpha-2a (180ug SC qW) with 250 mg REP 2139-Ca. Patients then transition to 33 weeks of pegylated interferon alpha-2a monotherapy. HDV RNA, HBV DNA, HBsAg and anti-HBs are followed every two weeks using standard assays (Robogene RT- PCR, Abbott RealTime HBV, Abbott Architect).
On treatment, observed HBsAg reductions are currently *5 logs in 6 patients (all \1 IU / ml), *3 logs in three patients and *0.5 to 1.5 logs in three patients. HDV RNA is currently undetectable in ten patients (*5 to 8 log reduction from baseline) with *3 and *5 log reductions observed in the other two patients. Substantial elevation (389–15,408 mIU/ml) of serum anti-HBs and the development of liver flares were only observed with the onset of exposure to pegy- lated interferon alpha-2a and was only evident in patients with serum HBsAg \1 IU / ml at the start of immunotherapy.
REP 2139-Ca is able to achieve rapid reductions in serum HBsAg and HDV RNA in Caucasian patients with HBV/HDV infection. REP 2139-Ca may become an important new therapeutic option for patients with chronic HBV/HDV infection.
46 Responses
Avatar universal
There should be another abstract dealing with HbeAg positive HBV patients only. I believe this will be an oral Plenary presentation, hopefully questions can be asked and answered.
1 Comments
yes, bellow...
Avatar universal
Serum HBV-RNA levels decline significantly in chronic hepatitis B patients dosed with REP2139-CA

Background and aims: The HBsAg release inhibitor REP2139-Ca may be a promising new treatment option for chronic hepatitis B (CHB) patients, however its effect on hepatitis B pregenomic RNA (HBV-RNA) is unknown. HBV-RNA levels during treatment with REP2139-Ca were determined and compared with HBV-DNA and HBsAg levels.
Methods: 12 Patients with HBeAg positive CHB participating in a phase 2 study were dosed with the nucleic-acid based amphipathic polymer REP2139-Ca for 20–38 weeks. Responders to REP2139 (defined as clearance of serum HBsAg) were subsequently treated with an add-on immunomodulatory agent (peginterferon alpha-2a and/or thymosin alpha-1). HBsAg, HBV-DNA, and HBV-RNA levels were determined at baseline, after 20–24 weeks of REP2139-Ca monotherapy, and either during a treatment-free follow-up (for responders) or during entecavir treatment (for non-responders). HBV- RNA was quantified by RT-qPCR using HBV-specific primers. Results: HBV-RNA levels were detectable in all 12 HBeAg-positive patients before treatment [mean 6.70 (SD 0.83) logC/mL], and were significantly associated with HBsAg (r2 0.33, p = 0.049) and HBV- DNA levels (r2 0.74, p \ 0.001). After 20–24 weeks of REP2139-Ca treatment, mean HBV-RNA, HBV-DNA, and HBsAg levels had declined significantly compared to baseline (all p \ 0.001). At week 20–24, HBV-RNA was undetectable in 8/12 patients. In 7 of these 8 patients, HBV-RNA remained undetectable during the treatment-free follow-up period (mean 21.9 weeks, range 7–27). HBsAg sero-con- version was achieved in 4/8 patients during follow-up (anti-HBs range 200–766 U/L).
Conclusions: In patients treated with REP2139-Ca, serum HBV-RNA levels declined significantly compared to baseline. REP2139-Ca may be a promising new treatment option for CHB patients.
Avatar universal
I am waiting for their presentation-slides...they are much more informative...probably in few days on their website.
Avatar universal
The third and last one:

Antiviral effect of therapy with REP 2139-Ca and nucleos(t)ide analogues against HBV in vivo

Treatment of human patients with chronic HBV infection with the nucleic acid polymer (NAP) REP 2139 results in the elimination of circulating HBsAg. In this preclinical study we evaluated a novel combination therapy associating REP 2139-Ca with tenofovir diso- proxil fumarate (TDF) and entecavir (ETV), in vivo, in the DHBV infection model.
DHBV-carrier ducks were treated for 4 weeks with normal saline (IP), REP 2139-Ca (10 mg/kg IP QD), TDF (15 mg PO QD), REP 2139-Ca + TDF or REP 2139-Ca + TDF + ETV (1 mg PO QD). Serum DHBsAg was monitored by ELISA and DHBV DNA by qPCR. After therapy cessation all animals were followed during additional 8 weeks. Total DHBV DNA and cccDNA were analyzed in autopsy liver samples by qPCR.
On-treatment antiviral responses were more marked when REP 2139 was combined with TDF or TDF and ETV. Sustained virologic responses (SVR) during 2 months off-therapy were only observed in the groups receiving REP 2139 alone or in combination with TDF or TDF and ETV but not in TDF-monotherapy. SVR consisted of stably suppressed serum DHBsAg and DHBV DNA and significant decrease in liver DHBV DNA and cccDNA that were more marked in com- bination-therapy groups. Importantly, SVR animals had undetectable liver DHBsAg as assessed by immunostaining analysis.
Antiviral performance of REP 2139 was sustained and enhanced by combination with TDF or ETV. Thus an interferon-free regimen of REP 2139 with TDF or ETV could improve antiviral response and shorten treatment regimens in HBV infected patients.
1 Comments
Thanks. Can you please cite the authors. In 2010 APASL in Beijing, Replicor had a poster about REP9AC.........
Avatar universal
Thanks for the abstracts :)
I wonder how much time we need to define those patients who achieved seroconversion as "functionally cured" ? 6m, 12m after finishing peginf ?
Avatar universal
what about starting a petition online to get this drug approved in europe?

medhelp is too small but maybe avaz or similar websites might help.i dotn think we can get it approved this way but we spread the word among hbvers about this drug
1 Comments
That's great idea ! Maybe some collecting money online for research ? There is over 200m of people chronically infected so if everyone give 1$...
Avatar universal
I know there is a Facebook group its Admin most of the time in here with us, i believe about 5000 HBV members in that group so this ppl they 'll definitely do a difference in the petition. Good luck!
Avatar universal
But stef2011 isn't moldovia in Europe where the clinical trial is on session?
Avatar universal
Yes it is and the difference between germany/italy or moldavia was only to save money while blood tests are made in labs in germany and us thats why i was thinking petition to get it approved

If you add hdv has no cure at all (hbv actually has a cure to block it) we may push all the public to join us.
For hbv they can say there are drugs to block it but this cannot be said about hdv, plus there are laws in some european countries that allows use of experimental drugs when there s no cure
Avatar universal
Avaz and thise websites may easily push all their members to join the petition if you put it like this: hdv has no cure and people die from this (this cannot be said about hbv of course),this drug has shown it can cure hdv and mild sides effects, this drug must be approved!

the small private drug company needs orphan drug approval for hdv

Off label use then is allowed for hbv too
1 Comments
Im in, and will find donations from many non hbv people as well.  
Avatar universal
Let's consider the Hep C community as well to help us for the petition though they got their own cure.
5 Comments
yes, lets try to organise it. The very reason why Replicor did testing on HBV + HDV should be to increase chances of being approved as there is nothing really useful for HDV people...
We can start with formulating a nice petition text which would include both HDV and HBV...then work on the best way for it to be signed by people
We may focus on hbv cuz if Repac will be approved one can us it off-label since "side effect" ;) may be functional cure of hbv as well.
Sorry, I mean "we may focus on HDV"
when you open Replicor's main website you'll see their main marketing slogan:

"350 million people have chronic hepatitis B. We’re developing the cure."

The reason their own marketing focuses on Hep B is because 300 milions of people have Hep B, whereas "only" 15 millions have Hep D (and in addition to that many of these 15 don't know they have it since Hep D is not a routine test in many countries). Advertisement is a numbers game, if we are about to collect more signatures than we should aim for both Hep B and Hep D.
Hi Aduiski,
Hep D comes either as a co-infection with hepb or as a superinfection in people with hbv infection. This is because hdv is incomplete virus and depends on hbv for replication. This means that those who're diagnosed as hdv positive are also hbv positive.
Avatar universal
is anyone expert on these websites to start it?

1 Comments
maybe we don't have comp engineer here, but we have to ask any of them that we know to built such a website. We must accelerate the exit of rep
Avatar universal
no we must not build a website we need support of online petition communities and jsut choose which ones are best for our purpouse, i know avaz as good one
3 Comments
Avazz is ok but for petitions only, not for collecting money
What about gofundme for collecting money, we could also have multiple avenues.  Nothing like a good old PayPal donate button on your community support website.  Could be as easy as a Facebook group.  But I agree that having a small webpage would be beneficial as a hub to tigh it all together, doesn't have to be fancy could be a one pager.  Just my opinion at the moment.  I wonder if medhelp would agree to help?
I do agree though that online petition community should be the first priority as I believe it will get the most exposure.  I think it's the most important for sure.
Avatar universal
Replicor to present pre-clinical and updated clinical data on REP 2139-Ca based combination therapy in chronic HBV and HBV / HDV co-infection at APASL 2016
NEW YORK, February 16, 2016 – Replicor Inc., a privately held biopharmaceutical company targeting a cure for patients with chronic hepatitis B virus (HBV) and chronic HBV and hepatitis delta virus (HDV) co-infection, will present preclinical and updated clinical data on REP 2139-Ca based combination therapies in HBV infection and HBV / HDV co-infection at the 25th Annual Meeting of the Asia Pacific Association for the Study of the Liver to be held from February 20 -24, 2016 in Toyko, Japan. Three presentations on Replicor technology will be made during the meeting:
HBV RNA is emerging as a potential new marker of viremia in patients with HBV infection.  In patients with HBeAg positive HBV infection, treatment with REP 2139-Ca and immunotherapy (in the REP 102 protcol), not only leads to reduction /clearance of HBsAg and HBV DNA and the appearance of anti-HBs but also to reduction of HBV RNA as well.  The characterization of the HBV RNA response in the REP 102 protocol was done in collaboration with the lab of Dr. Hendrik Reesink at the Amsterdam Medical Center, and will be presented by Dr. Reesink in the Presidential Plenary Session on February 22nd.
An update on the clinical response data from HBV /HDV co-infected patients completing REP 2139-Ca / peg-interferon combination therapy and transitioning to peg-interferon monotherapy in the REP 301 protocol will be presented in an oral presentation on Feb 22nd (O-130).
A poster presentation on the effects of combined treatment with REP 2139-Ca and tenofovir disoproxil fumarate and entecavir on serum and liver virema in vivo will be presented on Feb 22nd (P-0329).
These pre-clinical and clinical studies continue to advance Replicor’s understanding of the antiviral effects of REP 2139-Ca based combination therapies and how these can be used to benefit patients with HBV infection or HBV / HDV co-infection.
For the APASL 2016 meeting and preliminary program:
http://www.apasl2016.org/prg_overview.html
1 Comments
just to remind, Replicor still recruits in Moldova and requirements are:

HBsAg> 1000 IU / ml at screening
HBV DNA > 10000 copies / ml at screening and HBe- so like 90% of us here.

https://clinicaltrials.gov/ct2/show/NCT02565719?term=Replicor&rank=3

Avatar universal
once we spread the word about hbv cure among few millions  hbvers we gain so much power that it is very difficult for regulators not to approve it
6359077 tn?1441486304
I am excited..  how to start?
1 Comments
"GoFundMe's fee is 5% from each donation you receive. WePay's fee is 2.9% + $0.30 per donation. You are agreeing with all terms." :/
Avatar universal
Mer971 we do have  some computer experts like Ram1982 & others in this group, he is a good man & 'll definitely get a help from him. Good luck Ram!
Avatar universal
& for sure there are some online freelance sites where they can build websites for profit.
Avatar universal
Like upwork.com
Avatar universal
First of all we need to summary, less or more, what will be the content and the target of the petition.
So what is the current state of Replicor registration process for HDV and when it may be approved when using regular track in comparison with fast track procedure, which I guess is a target of this petition ?
To whom we target that petition ? FDA ?
Avatar universal
we have to check who approves drugs in europe or the countries where approval is easier in europe

once a drug is approved in one EU country it is approved in all others automatically.not free by healthcare but approved if one can buy it or produce it
1 Comments
totally agree, we must look for a pharmaceutical company in europe. Someone got to do this, got to see how are the procedures of approval for orphan drugs. Spread the word
Avatar universal
Probably its EMA:

http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000109.jsp

"The centralised procedure is compulsory for: ... viral diseases"
Avatar universal
OK thanks Sorte at least we knew now whom to send the petition.
2 Comments
Maybe we must talk to Margaret Dudley, how she handled to get petition for accelerated approve of Hep C,
I also think this is a great idea.  
Avatar universal
That's great idea
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