Upcoming HBV treatments

The Hepatitis B foundation has a fantastic up-to-date list of all the Hep B treatments currently under development here.

Use this thread to discuss any new HBV drugs in trials or under development.

Edit: As mentioned by @PuallyHBV, the FDA in conjunction with the Hep B Foundation ran a patient-focused drug development meeting (recording and report here) in June 2020 that might be of interest to forum members here.

TT

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Hi Thomas,

Couple of years ago there were publications about very promising medicine Birinapan which combined with entecavir gives very high chances to eliminate hep B completely. As I understand the research is made in Australia. Do you have any information on this? I cannot find it on Hepatitis B foundation page

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Hi Olga,

Yes, Birinipant was under research at the Walter Eliza Hall Institute and went through a phase I clinical trial: https://clinicaltrials.gov/ct2/show/NCT02288208. It looks like there were some side-effects associated with the trial and it was terminated. I am not sure if research is continuing on this line (e.g. reformulation or trying different doses/delivery methods).

Thomas

Hi Thomas,

I don’t know if this is the right posting area to put this so please move it to wherever you think best.

Just in case anyone hasn’t received the email from The Hepatitis B Foundation about the live patient focused drug development meeting from back in June, here is the link to the video and the full downloadable report:

https://www.hepb.org/news-and-events/patient-focused-drug-development-meeting-virtual/

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Thanks for finding this link, Pually.

I’ve moved it here and put the link in the OP so that others can find it easier.

Cheers,
TT

Make sure you check out the downloadable report because it’s the new final complete compiled data from survey participants and panelists, etc.

The Hepatitis B Foundation just sent me the new updated link in email today.

I went to the live meeting and got to see you as one of the professional panelists.

Yeah, sorry if i look unenthusiastic. I think it started at 4am Australian time…

Off all the drugs under trials currently, are they all intended for treatment of HBV only or cure?.
It seems the drugs under trails are more or like the same once which are used for treatment currently.

Dear @Wadani1,

The movement in the field is that any drugs that are developed are aimed at curing HBV (either functional cure or complete cure). Whether they can actually cure patients is tested in clinical trials. Scientists can’t control what actually happens in nature when we first test these therapies.

The reason behind aiming for cure is that the drugs we have at the moment for HBV treatment (entecavir and tenofovir) are really quite good at suppressing the virus already and are very safe, so it’s hard to improve on them.

Cheers,
Thomas

Hi Thomas, hope all is good.

The following article came to my attention about the goat’s rue/metformin

Any chance you are aware of any studies on how goat’s rue/metformin affects HBV decease?
It seems to be amazing medicine

Isn’t Metformin (not Goat’s Rue) for diabetes? Doesn’t it have its own set of side-effects?

Sorry if this is not relevant and it’s different than what I am thinking of.

Yes, currently it is used to treat diabetes. But according to the article it has huge overall positive impact on body and health. Thus, it reduces risk of cancer development significantly, makes the patients with diabetes who takes it live longer than even healthy people. According to the article it also suppresses viral and bacteria activity.
So, it would be interesting to study this medicine in relation to HBV, in particularly given the higher chances of HCC development. I wonder if such studies have already been made or in process

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Dear @OlgaP,

I had not actually heard of using metformin as an anti-HBV drug, so I did a little bit of research.

Looks like there is an interesting study showing that metformin does decrease HBsAg, HBeAg and HBV DNA levels in a petri dish: https://onlinelibrary.wiley.com/doi/abs/10.1111/jvh.12187. I think this has justified a clinical trial that is ongoing in China: https://clinicaltrials.gov/ct2/show/NCT04182321.

I do not think however it will have a “huge overall positive impact”. A paper looking at HCC recurrence showed no effect at all of metformin in preventing it: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247231. Also, there was a huge study of more than 700,000 people which found no effect of metformin on liver cancer rates in HBV patients: https://journals.lww.com/md-journal/Fulltext/2015/02020/Cancer_Risk_in_HBV_Patients_With_Statin_and.5.aspx (there is a slight protective effect from statins, and a little more if you combine statins with metformin).

Cheers,
Thomas

Thomas, many thanks indeed for doing this research. The results of the clinical trial will be ready in December 2021, so looking forward to it

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And what about antisense oligonucleotides? Perspectives?

Dear @m.chersich,

Welcome to the forum and thanks for your question. I think that antisense oligonucleotides (I’ll call them ASOs because it’s a long name to type) are based on good science and have a known mode of action. One of the major challenges have been to deliver them to the liver, but huge progress has been made in this area and it looks like this is pretty safe and efficient now. In pre-clinical models, ASOs have shown good effect on HBV DNA, HBsAg, and HBeAg.

The problem is it’s difficult to test the effect of ASOs on cccDNA because of the lack of proper models we have for a chronic HBV infection. The hope is that the reduction in HBsAg will restore some immune response, which will wake up and start clearing infected cells. Even if this is not achieved, ASOs may at least help achieve a functional cure (i.e. loss of HBsAg, which would mean you could stop taking antivirals).

My feeling is that there is promising data out there because a fair number of companies are investing in this strategy. Trials are currently ongoing, so we should find out soon whether they live up to these hopes!

@john.tavis might have some further things to say about this as a drug-discovery expert.

Cheers,
Thomas

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Dear M. Chersich,

Welcome to the Forum!

I am Director of the Saint Louis University Institute for Drug and Biotherapeutic Innovation, and much of my lab’s research is on anti-HBV drug discovery. Thomas is correct in his interpretation of ASOs. They are promising and a number of companies and academic labs are working on them. There is no question that they can work vs. HBV because they cause degradation of the HBV mRNAs, which suppresses both viral protein production and viral reverse transcription. The devil as always is in the details. Delivery to the liver is a major challenge for those sorts of molecules, but those problems are rapidly being surmounted. They will be sensitive to sequence variation in the HBV genome and development of resistance mutations because it typically takes only 1 or a few nucleotide variations to block binding of the ASOs to the HBV mRNAs. However, that can be managed by using mixtures of ASOs with the common variations in them. Another problem that is being worked on is that they are not always adequately powerful in suppression of HBV mRNAs, but that should be manageable with proper ASO design and use of cocktails of different ASOs. Overall, ASOs are very much worth pursuing, and some very good labs are doing so.

I hope this helps.

John.

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Hi , i have heard of a cuban drug called Nasvac or HeberNasvac… the drug is in phase 3 clinical trials and they already trying to test it with other drugs but i have not heard from them since 2020

Has anybody have any news about Nasvac? When will it end phase 3 and be available for public ? All reports seem positive for funcional cure…

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Hi @ROP_10,

Welcome to HepBCommunity and good question. I hadn’t actually heard of Nasvac before you mentioned it and looked for some information about it. It looks like a cool technology of vaccinating someone by a nasal inhaler. I then looked at the published data from a Phase 3 trial of it: Treatment of chronic hepatitis B naïve patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment controlled phase III clinical trial). In short, it did lower HBV DNA levels (~99%), but it worked about the same as interferon. You’d probably get much better effect with tenofovir or entecavir. There didn’t seem to be any effect on HBsAg levels, which is what we’re aiming for these days.

Other studies found that it did induce some antibodies in tree shrews, which is an animal model of Hep B (Intranasal vaccination with HBs and HBc protein combined with carboxyl vinyl polymer induces strong neutralizing antibody, anti-HBs IgA, and IFNG response - ScienceDirect).

A more recent pre-print suggests that it may reduce HBsAg levels (HBs Antigen Reduction and Anti-HBs Induction Through the Nasal Administration of a Therapeutic Vaccine Containing HBs and HBc Antigen in Patients with Chronic Hepatitis B Virus Infection by Osamu Yoshida, Sheikh Mohammad Fazle Akbar, Yusuke Imai, Takahiro Sanada, Kyoko Tsukiyama-Kohara, Takashi Miyzaki, Taizo Kamishita, Teruki Miyake, Yoshio Tokumoto, Hayato Hikita, Masataka Tsuge, Masahito Shimizu, Mamun Al Mahtab, Julio Cesar Aguilar, Gerardo Guillen, Michinori Kohara, Yoichi Hiasa :: SSRN), and cure ~10% of their cohorts, but I can’t access the actual paper to verify this. I guess we’ll just have to wait…

TT

Cheers,
Thomas

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Because they are adverting the NasVac as the next “functional cure”. …maybe a combination of NasVac + Entecavir could be the future’s new treatment for permanent functional cure.

I don’t understand why is taking so long for Nasvac to be approved . It’s being used in Cuba, Bangladesh… French Abivax got them marketing back in 2015… now called HeberNasVac. Common it’s 2021!!! What is going on?

In your opinion, is it possible to fast-track all phase 2 trials so it becomes available to the public? How was it possible with SARS CoV 2?

The Germans have another technique , “TherVac B”…100% cure with mice and it’s not functional cure , it is THE CURE!! But unfortunatly we have to wait 10 -20 years if , it works. Just thinking about it makes my liver hurt.

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