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GS-4774

Has anyone heard anything about Gilead GS-4774?  This is a Tarmogen T cell immunity stimulator.  
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Hi All,

Any news on drugs to cure Hepatitis B?
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Because its all about the money!
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All the new medications we.are talking about here can help us. The big question why they are not being released.
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Yes but a flew would  be a weak virus no??

Where as with HBV it must be stronger or  there must be a weakness in our system somewhere for it not to clear the virus.

Mate you can  see some people on here have developed surface anti bodies but still have HBSAG which is rare but then what can they do?

Thats a sign there is an immune  response but there's still some forrm of weakness needs addressing.

I do agree with you in terms ultimately in the end it has to be the immune system that fights the virus off and delivers our personal freedom but its just a question of how we get this to happen my brother
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When you have a flue you have billions of its viruses in your body too. Look at viral kinetics. But our boby makes interferon and as much of antibodies to counter and win. Win HBV it is the escape mutant that establishes a chronic infection.

So viral load in itself is a greatly manipulated thing to sell medication. Or to prove its efficacy.  
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I hear what your saying and don't particularly disagree with you but the problem being if the immune system is swamped by viral DNA then that could be tricky. However if its suppressed followed by immune booster i like the 91% of people who did the NUC's + Peg  might be a good combo.

But I also have the suspicion it will  be TAF 3years + GS9620 = Immune clearance

Think it would be the most lucrative by a mile + Gilead can say we have  a "cure"  ramp up the price for GS9620 to astronomical levels give out the TAF fro free to so they can appear not be heartless and ease political pressure on thesmelf.

Just my thoughts/opinion

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What is upsetting to see is that companies like Gilead dont listen. You cant even get a responce. No one even comes here and openly engages in a dialog with patients on how can all this be done better.

How to improve clinical trials. That reguar clinical trials are really a joke given so few patients and so.few possibilities in drug combos.
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Shutting down mitochondria in the body is equivalent to power a city lights with power plant reactors turned off. In simple terms that is. But for advancedcancer and HIV that was the choice they had to make. To prolong life. But even with those diseases they admit that immune system gene therapy saves lives. Cancer can be cured better and faster with immune therapy based on  the same Ebola plantibodies treatment and so can HIV.

You design anti viral anti tumor antibodies that multiply within the host body. And nature takes care of it like a common flue or cold.

And they are being silent about this. Doctors dont like hearing about this. That the so called medical standard today when it comes to treat cancer aids and hbv is not where it should be.
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You know looking at it based on what we know it is the immune system of individual that has to do all the work. They are using this vaccine with a nuc. That causes mitochondrial toxicity  thus is immuno suppressive. So the effect that this vaccine could have with interferon or zadaxin may not be there.

Look at Repicor they use it with peg or zadaxin. GS4774 is also said to lower  hbsag. So logically would be to use it with immune system booster. But  no they still want it to be their own brand 1-2 punch.

So this trial may be a wash of nothing in end. But medication may actually work.

I cant say enough how frustrating it is to see ALL the business BS that is going around HBV treatment. Half the time medical students that are doing these clinical trials with their university proffesors have NO clue what so ever what these drugs do to the whole body. That immune system quality depends on the amount if toxins other infections - heath of teeth of a given person.    

That it is not just give the medication and cured. We are not at this Point yet. Unless of course they make antibodies against HBV for us like they did with Ebola.

Why not give GS4774 with Imiqumod. GS9620? That will give a better effect no doubt. Because NUCs really should not be used for HBV. These are really strong and toxic drugs designed to slow down HIV. AND HIV infects every living cell in the body. And so do these drugs.
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Yes but would Mono be more lucrative? I mean terms of Gileads earnings from this?
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9624973 tn?1413016130
I will ask my doctor, hopefully whe will kniw more about this. But question , is it worthing trying to get this phase 2 trial or better wait for something better
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9624973 tn?1413016130
I am from romania, what are the requirements to qualify for this studi ? I never been on meds and i have very high hbvdna and hbsag and no liver or damage i think.
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Maybe I can finally make one of these! I tried 2wise and there was always something.

I still think they need to use these vaccines with interferon to boost their effect. Maybe with TDF to hit HBV from all three angles.
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Another great post. Gilead has also begun a Phase 2 trial of GS4774:
"This study is to evaluate the safety, tolerability, and efficacy of GS-4774 in adults with chronic hepatitis B infection (CHB) and who are currently not on treatment. Participants will be randomized to receive tenofovir disoproxil fumarate (TDF) alone or GS-4774 plus TDF for 20 weeks. After Week 20, GS-4774 will be discontinued. All participants will continue on TDF and will be followed for an additional 28 weeks. Following completion of the 48 week study period, all participants will be eligible for a 3 year registry study."
The trial will take take place in the US, Italy, Canada,Korea, New Zealand, Romania, and Taiwan.
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Recent paper on GS-4774 got published in Vaccine.

http://www.sciencedirect.com/science/article/pii/S0264410X14009530
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Yes and no. The Chinese had investigated three 3 therapeutic vaccines in the last few years, two by listed companies, one by a well-known academic. The two by listed companies, both completed Phase 2 clinical trials, but results were disappointing, no or slightly better than the control groups. Being commercial companies, they disclosed the minimum information and outsiders cannot learn from their experiences. The one investigated by Prof Wen, a novel HBsAg and HBsAb complex, completed phase 3. Again the results are no better than the control(placebo is Alum) group, even though the loss of HbeAg was as high as 30%. I am sure lessons will be learned from this study, one of them being too much and too frequent injections of the vaccine, driving, as Studyforhope described, the immune system "crazy" and exhausted.

The France has also been studying several therapeutic vaccines, but progress is very slow.

Cuba has of course completed a successful Phase 3 of their NASVAC vaccine. Unfortunately, we don't know whether it will be further developed.

I am sure a lot of the concepts behind these vaccines were tested on animals. Prof Wen when she began her work, spent a million US dollars to purchase a genetically modified mice from overseas.
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As always, THANKS very much for the kind explanation.

Is this therapeutic vaccine the first such attempt by the pharma industry?  Any idea if this has been tested in primates or mice?

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I wish I can give you a good explanation, but it is a bit beyond me because immunology is so complex. I will try, but others can correct me.

The current HBV vaccine consists of the HBsAg antigen, a protein. It is very effective in inducing the production of HBsAb, antibodies to the surfact(envelope) antigen. These circulating antibodies will attach to the surface of circulating HBV viral particles and prevent the viral particle from entering a liver cell - therefore no infection.
However, in order to cure patients with liver cells infected already by the virus, we need to induce production of cytotoxic T cells, so called cd8+ T cells that specifically recognise HBV infected liver cells, thus killing or controlling these infected cells. Because HBV viral proteins are produced inside infected liver cells, the surface of these cells express epitopes of these viral proteins in MHC class I complexes. So a therapeutic vaccine has to induce the production of these HBV specific cd8+ T cells.  
In order to induce the production of these T cells, special immune cells must present HBV viral antigens in MHC class 1 and 2 complexes. GlobeImmune scientists believes they can achieve this. GS4774 consists of heat killed yeast cells. These yeast cells have inserted into them, DNA that codes for the production of HBV surface, core, and x proteins. So I presume these cells, before they were heat killed, produce these HBV viral proteins inside the cell. When these cells , heat killed and then injected into a patient. The patient's APC (antigen presenting cell) such as the dendritic cells, will engulf these heated killed yeast cells, process and present various HBV viral epitopes in both MHC class 1 and 2 complexes to the immune system. So HBV specific Cd8+ T cells will be produced. Also antibodies to the yeast cells are also produced, the scientists say.

So this is the first half of the story. But a chronic HepB person already has these HBV specific cd8+ T cells, but they are not "effective" due to various factors caused by the immune braking system and HBV evasive mechanism. Whether these freshly produced T cells will meet the same fate or not is what we have to wait and see.

Just my own understanding..

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Hi Stephen

Just curious, how is a 'vaccine' GS-4774 different from a standard hbv vaccine that is used to immunise a person?

Thanks.
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Thank you for posting and hope that you will qualify for the clinical trial. It is a pity that quantitative HBsAg assay is not yet commercially available in the State, together with hbvdna, it can lead to a better stopping rule for taking oral antivirals.
Please keep us posted.
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I went for the screening phase today and await for test results. Hopefully everything is good to go so I can qualify for the study. Been on adefovir and entecavir since 2005 and wonder if I'll ever be off antiviral medication.
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Dont worry about it. This is a vaccine. I dont think anything bad can happen.
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Thank you for posting. GS-4774 had undergone a phase 1 trial and the results were presented at the recent AASLD meeting:

http://www.natap.org/2013/AASLD/AASLD_74.htm

Please keep us posted if you do decide to join the trial.
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Ive been asked to be part of this study for Phase 2. I am scared about the side effects of this. I have been on Barraclude for 4 years and dont know when I will be take off of it. Thank you.
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