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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Hi @ROP_10,
The reason it takes so long is the efficacy data is not there yet. For Nasvac, the 10% functional cure rate was something like 4 out of ~40 people, this is quite a small trial. And it’s not clear what the control arm looked like. Larger studies are needed and sometimes the effect of these drugs shrink dramatically when testing in more diverse populations (for many different reasons).
For TherVac, there may be promising data in mice, but this is not a 100% accurate model for a human chronic infection (again, for many different reasons).
This is the stringency and tough trials that all hep B drugs have to go through to make sure that these are safe and effective medicines. We are dealing with a pretty high bar at the moment; the currently available antivirals are just daily pills that can slow liver disease down with very rare side effects.
Any developing therapy that does not work as well or suddenly generates adverse effects are going to receive a lot of scrutiny to make sure it is worth it for people with Hep B.
I hope that gives you a bit of insight into why it takes so long.
Cheers,
Thomas
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Hi Helpme786,
There are many types of “cures” once you dive into the details. I’ll discuss the 2 most commonly considered types.
By “Cure”, you are probably referring to what scientists call a “sterilizing cure”. That is when all traces of HBV are eliminated from the body, drugs are no longer needed, and the risk of disease progression is no higher than for someone who never had HBV. The scientific community does not think this will be achievable due to HBV’s propensity for integrating its DNA into the patient’s DNA. However, this is not the only type of possible cure.
The goal of the scientific community now is to generate one or more “functional cures”. This is defined as having no detectable HBV DNA or HBsAg in blood six months after termination of treatment. As near as we can tell, that will provide essentially as much benefit to the patient as a sterilizing cure. However, it may be hard to identify everyone who has achieved a functional cure because the integrated HBV DNA can make HBsAg even if the “live” virus has been eliminated. That is a definition and measurement issue that we need to work out.
Personally, I really hope that people who achieve a functional cure either naturally develop anti-HBsAg antibodies, or that they can be vaccinated against HBV. That would help stop viral relapse and reinfection. However, development of antibodies is not part of the current definition for a functional cure.
I hope this helps.
John.
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Dear Dr. @john.tavis
I see you join HBV Cure Singapore last week. Is there any good news for HepB Patient from the conference?
Hope you can share the update to the community.
Thanks
Dear @senhour,
Yes, I was at the Singapore HBV Cure meeting last week. I enjoyed it very much and learned a lot. There have been no breakthroughs in HBV cure yet, but there has been steady progress in increasing the functional cure rates through combinations of novel drugs. Most of the successful combinations that I heard about are giving 25-30% functional cure rates, which is a lot better than the <10% rates we have now. Most of the curative combinations still include interferon alpha and require extended treatment (1 year or longer), so we have a long way to go to get therapies to where we want them. But I was very heartened to see that the hard work of the scientific and patient communities is beginning to pay off! I’m sure further steady improvements will continue as we learn more. New data on the next wave of clinical trials will be released at the EASL meeting in Vienna later this month. Hopefully, those studies will show continued improvements.
John.
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