Is Cure coming in future?

Hi doctor @ThomasTu ,

I saw you on YouTube that you are participating in clinical trails for cure hepatitis b.

I saw some trails going to made for hepatitis b cure.
When is nasvac therapeutic vaccine is going to be released?
How many phases of clinical trails will be there?
Why is thervacb show so much promising on curing hepatitis b?
Is that mouse model is successful in any previous trails of other therapeutic vaccines?

I’m like the most people who live with hope…

Dear Helpme786,

I’m a senior HBV virologist and director of a local drug discovery institute. Your questions about a cure coming are very good. The good news is that there are an enormous number of drug and vaccine strategies being tried in Universities, small biotechnology companies, and major pharmaceutical companies. I am personally confident that major improvements in therapy for HBV will arrive within 5 years, or perhaps a bit longer. However, please remember that this is just my personal opinion, and that it is impossible to predict the pace of scientific and medical advances. We are working at the edge of the unknown, and the complexity of the problem is truly daunting.

As to your specific questions:

  1. The international standard for clinical study design is in 3 phases. Phase I is in small numbers of healthy folks and tests safety and potential dose ranges for the new therapy. Phase II is a larger study to further look at safety and to identify the dose that should be used therapeutically. Phase III is a large study that looks at safety and how well the therapy works. In some cases, the phases can be integrated together, but in all cases all 3 major sets of questions need to be studied.

  2. ThervacB is showing such promise because it takes advantage of decades of study of the immune system and understanding of HBV biology. It looks great in animals, and I really hope that plays out in the clinical trials. Pretty much all of the prior therapeutic vaccine trials in the animals were only moderately or not promising, but each one contributed more understanding that helped guide design of the next one.

  3. The nasvac vaccine also takes advantage of advances in understanding of HBV and immunology. It appears to be working in some people in the early trial data reported. Short-term drops in HBsAg were modest, but the immune response against HBV appears to be on the “slow but steady” path, with some patients achieving functional cure at later times. Note that this trial data is from a small number of people, and so larger studies are needed. However, it looks like they may be onto something!

I hope this helps.



Thank you so much for a breif explanation sir, I hope everything will be settled in future. Soany like me don’t know how they get this virus untill they went for operation or some medical blood checkups. I’m an engineering student and I never did sex or blood transfusion before. Doctors thought I may got this through RMP doctors while giving injection for normal viral fever… But now I’m an victim… I’m strong and having high spirits. I never dispointed…

My last question : under taking medications can I live my normal life and going to my job… I’m working in a small software company in night shifts.

Question 2 : can you please clearly explain how can I stop transmitting to my wife after marriage in future… Can I make a normal sex after she got vaccinated… Or still do I need to use condoms.

Thank you doctor

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Dear @Helpme786,

Thanks for your questions and thanks @john.tavis for your informative answers.

  1. You can definitely live and work normally. The only thing is remaining under monitoring (visiting a doctor and blood tests every 6 months) and taking your pill each day. Otherwise, the majority of us with hep B are living like everyone else.

  2. As long as your wife’s anti-HBs antibody levels are high enough (you can check this with a blood test, the threshold is 10mIU/mL), she will be protected.



hi @john.tavis & @ThomasTu ,

Today i came with new question :slightly_smiling_face:.

1)what is RNAi gene silencer and TLR-8 agonist mechanisms?
2)could you please tell me about the results of VIR-2218 & Selgantolimod (GS9688) in phase 2?
3) please comment on these combinations 1)VIR-2218 and VIR-3434, 2)VIR-2218 and Selgantolimod

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Dear Helpmegod,

An RNA silencer is a drug made from a small piece of RNA (kind of like a DNA) that has been modified to make it more stable and be able to get into cells. They bind to a bigger type of RNA in cells called mRNAs and block mRNA function. That stops production of the viral proteins from the mRNA, blocking viral function.

TLR8 is a “pathogen associated molecular pattern” detector that detects foreign RNA once it gets into the cells (in a part of the uptake pathway called “endosomes”). It normally detects RNA from a pathogen and then triggers the immune system to fight the pathogen. An “agonist” is a molecule that binds to something and turns it on (vs. an “antagonist” that binds to something and turns it off). A TLR8 agonist is therefore a drug that binds to TLR8, turns it on, and triggers the immune response to attack HBV.

In a completely irrelevant but interesting note, TLR stands for “Toll Like Receptor”. TLRs are named after a German word that can be translated as “Cool!”. This is because the first member of the class was identified in studies with mutant fruit flies that looked interesting under a dissecting microscope. The researchers were German, and the lab director looked through the ‘scope and said “Cool!”.

VIR-2218 is an siRNA drug in phase II trials.

Selgantolimod is a TLR8 agonist in Phase II trials.

Combining an siRNA and a TLR8 agonist together in a combination therapy makes sense scientifically. The TLR8 agonist would help turn on the immune system, and the siRNA would help suppress viral replication and reduce the amount of HBV proteins in cells. That is important because some of the viral proteins partially block the immune system. Overall, this strategy focuses on ramping up the immune system to kill HBV infected cells. The risks with this strategy are that if the immune response becomes too vigorous a patient may get ill from killing too many HBV+ cells too fast. However, that does not seem to be very likely to happen as the problem with most siRNAs and the TLR8 drugs when given by themselves is that they did not attack the virus as hard as we had hoped (they worked, just not spectacularly). However, only clinical trials can really find out if a combination works in people.

Note that this is only one of the very many logical drug combinations being considered now.

John Tavis


When we talk of a cure, are we talking about the potential to no longer be infectious to other people?
That is truly what I’m struggling with now, not being seen as a parasite or a danger to other people. In my country most people 33 or younger have been vaccinated so I don’t feel I am putting others in danger with my bodily fluids but it still is something I think about on the daily.
Of course when talking about myself as a patient no longer having a concern about my own liver health, I am genuinely awaiting a functional cure that will rid my body of this disease!

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Dear @Bonzai123,

Welcome to the forum and thank you for your comments. I agree completely with your points. I feel like there needs to be two different discussions:

  1. A cure to prevent transmission: this is currently termed a “partial” cure in the academic/clinical field. This means you have extremely low risk of transmitting it to other people because the circulating virus levels are very low. This can be achieved currently with continual antiviral treatment with current medications, but it would be great if this can be induced with something with a shorter course. I feel like this would change people’s lives around the world if it was accepted by society - e.g. not being considered a threat to others and being able to escape a lot of the discrimination in society.

  2. A cure to prevent disease progression: this is a different beast. You can stop virus production in the blood, but that doesn’t necessarily mean the risk of liver damage or cancer is gone. This is a much tougher assignment and scientists think that it may require HBsAg-loss (a “functional” cure) or complete elimination of cccDNA (a “complete” cure). Functional cure is really what the field is focussing on.

I hope this makes it clear.


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Thank you Thomas for your response.
From your point 1 am I to understand that there are currently antivirals that would prevent transmission to a sexual partner especially if they are vaccinated?
I am waiting to meet with my specialist. I was diagnosed about 2 months ago and still trying to source a lot of information on my own.
The hope of a functional cure within 5 years or more is really what I’m clinging to but currently grappling with understanding the information out there.
Your community here has been a godsend.


Hello Thomas, I came across this article online. Can you give some input into this? Is that mean the cure is coming soon, like within couple of years? Do you know the process after phase II trial for the drug to be approved for general population and the timeline? Thank you.


Dear @Bonzai123,

Yes, lowering viral load with antivirals like tenofovir and entecavir will dramatically reduce the risk of transmission. If they are fully vaccinated, then the risk is negligible.

Hi @AlexH,

It’s too soon to say whether this will translate into a cure or not, as these are just phase 2 trials at the moment. These sort of trials take years, so it’s difficult to say when these treatments would reach the general public if they were successful. For good and safe medications, money is the key to speed: the more investment into research and development available, the faster it’ll be. We’ve seen this with COVID medications that it is possible to drive quick results as long as there is the money to do so.

@john.tavis, @rgish, @tim.block or other @ScienceExperts might know more about this and be able to comment further. I am not attending this conference because it is out of my time zone, so I have not been able to see the data.


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Hi @AlexH ,

VIR-3434 is a neutralizing monoclonal antibody that in essence artificially provides some immunity to HBV infection of cells as long as it stays at a high enough level in the body. It is a high-tech version of HBIG that has been approved for many years. It will not provide a cure on its own, but could be really useful in a combination therapy.

VIR-3434 performed well in the Phase I safety trials and is in Phase II (expanded safety/dose assessment and the start of testing efficacy). If the Phase II results are good, the normal pattern is to go into a large Phase III trial that continues to look at safety and tests efficacy. To do so, the Phase II results need to be finalized and evaluated, the Phase III trial needs to be designed based on what was learned in Phase II, and the trial needs to be done. If the Phase III trial is successful, VirBiotec needs to submit new drug applications to the various national regulatory bodies (FDA in the USA, European Medicines Agency for the EU, etc), and the regulatory agencies need to conduct extremely detailed reviews of the application before approval.

There is no guarantee that any drug candidate will survive this gauntlet. In addition to scientific barriers such as insufficient efficacy or safety problems, there are all sort of business and regulatory issues. Can the company raise the tens to hundreds of millions of dollars required to finish the trials and apply for a license? Will the regulatory agencies conclude the drug is “non-inferior” (ie, not worse than) competing licensed drugs? Will Vir Biotec be able to produce the drug at a price cheap enough to allow them to make money (to pay back the ~US$1-2 Billion spent in drug development and then make a profit)? Is the patent protection solid enough to prevent competitors from simply stealing it and selling it on their own?

In short, drug discovery/development is not for the faint or heart! However, I remain very optimistic. There are so many drug candidates for HBV in all stages of development that are looking good for the stage they are at that some of them will certainly make it through to licensure. My guess (and it is only a guess as the pace of science cannot be predicted) is that better therapies will start appearing in 3-5 years, with potential curative therapies in around a decade.

Rest assured, the scientific and medical communities are working as hard as physically possible to improve therapy and develop a cure.



Hello Experts,

What is your view on below result of Arrowhead.

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Dear Hope for Cure,

The results of this trial are difficult to fully assess without understanding the baseline HBsAg values of patients who were enrolled in this trial. This is an important consideration since only HBsAg declines from baseline are presented instead of raw HBsAg values (which is preferred). Additionally, one of the drugs used in the combination regiment in this trial (the RNAi compound) works better with low HBsAg. Unfortunately, these details were not fully disclosed but we know that patients with low HBsAg were allowed into the trial since one of the patients in the placebo control group spontaneously achieved functional cure.

No patient in the trial achieved HBsAg loss (except for the functional cure patient in the placebo control group). Although some patients achieved the trial-defined criteria for stopping all antiviral therapy, this was a HBsAg reduction threshold more than 1000x greater than the level considered to represent HBsAg loss [< 0.05 IU/mL]). Unfortunately, HBsAg began to rebound when antiviral therapy was removed, which is not a good sign. Additionally, the patients where all therapy was removed, the HBV DNA values were not disclosed in the follow-up which is puzzling.

Finally, transaminase flares are an important part of functional cure. These are events that signal the immune system removing infected cells from the liver. We know that transaminase flares accompany HBsAg loss and functional cure in approved therapies such as pegIFN and also accompany HBeAg conversation with therapies like ETV and TDF. Transaminse flares are also very common in current clinical trials with nucleic acid polymer (NAP) based combination therapy, which is accompanied by high rates of HBsAg loss and functional cure (see the posting on NAPs in the 2022 Research Showcase). Unfortunately in this trial transaminase flares were virtually absent.

We need to see more data from this trial to completely asses the performance of the combination therapies uses, including longer follow-up, HBV DNA values during follow-up when NUCs were removed and most importantly, raw HBsAg data.


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