New Drugs to cure Hep B?

Hi all,

Thanks for adding me to this group. I was diagnosed back in 2006 ( I am 40 years old now) and it’s great to see how many support groups and communities there are for HBV sufferers like myself.

I’m currently on Tenofovir and have been on this for quite a number of years now. I’m also monitored via blood tests and US every 6 months and so far results have been good.

As with my questions to my liver nurse every annual meeting, I ask ‘any news of any new drug in the pipeline that will kill off the disease’. Every year the answer is ‘no’.

What do the scientists if this group reckon? Is there a possibility or will our best defence be the drugs that suppress the virus, with the hope it does not progess to liver cancer?

TIA,

Pete A

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Hi Pete,

Welcome to the forum, really great to have you here. Great to hear that you have maintained regular monitoring and that you haven’t had any trouble with ongoing medication.

As a scientist, I think I can give a reasonable response to your query. It’s true that there are no drugs available yet that will cure a chronic infection, but it’s also true there have never been so many anti-HBV drugs in clinical trials. Hep B foundation has a list of drugs in clinical trials here and you can see there are dozens.

There is a long wait because lot of work, time, and money has to go into studies, so that we can be really sure that they’re safe and work for everyone. I really can’t predict which one of these might end up being the cure or how many will be discontinued because they are not effective enough or too toxic, but I feel confident that there will be something available in the near future. The feeling in the research community is one of hope, rather than just survival and frustration… well mostly, there still is frustration that Hep B research is not as well funded as it should be (e.g. compared to HIV and Hep C in the past), but that perhaps is another conversation.

The best thing we can do in the meantime is prevent progression of the liver disease with a healthy lifestyle and following sound medical advice as well as possible.

Cheers,
Thomas

Dear Pete,

I’m a senior HBV virologist with an active program in anti-HBV drug discovery. Over the last 5-8 years there has been a major explosion in efforts in academia and the pharmacological industry to develop new, curative therapies. The first wave of these molecules are in Phase II clinical trials and some of them are performing remarkably well. There are also a huge number of other projects at earlier stages of development. It is evident to those of us in the research community that a cure will require combinations of drugs that work well together. The outlines of which classes of drugs will be useful is becoming clear, and work is commencing on figuring out what combinations are likely to be best.

It is impossible to predict the rate of scientific advances, so I cannot say when improved therapies will be become available. However, I am extremely optimistic that this will be measured in years, not decades. Until then, Tenofovir is an outstanding drug, so I encourage you to keep following your physician’s recommendation and to keep your ears open for therapeutic advances.

John Tavis, PhD

Greetings,

Thank you for adding me to this newly Hep B Community. I am a 62 years Asian female and on the Baraclude med for more than 10 years. My ALT maintains low and undetectable DNA for many years. Should I stay with this medication for the rest of my life? Also, I am always concerned about the drug in my system; what kind of impact will do in the long term?
Is there any hope for us to see the “Cure” in my lifetime?
thanks
Jo

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Hi Jo,

I’m delighted that your therapy is keeping your ALT low and your DNA levels undetectable!

Baraclude (= Entecavir) is very well tolerated by most people. As with any powerful drug, there are some side effects. I’m a bench scientist so I am not super familiar with the specific issues, but overall Baraclude is very well tolerated by the large majority of patients for a long time. Your physician will know the details, and ongoing clinical monitoring (as you are doing) is important. Long-term side effects are possible with extended administration of any drug (I have 2 chronic conditions requiring daily medication, so I worry a bit too), but to the best of my knowledge long-term surveillance for serious issues with Baraclude is not turning up things to be concerned about. Your physician will know the details.

As to a cure in your lifetime: I am very optimistic. It is impossible to predict the rate of scientific advances, but the entire HBV drug discovery field is excited about obtaining a cure relatively soon. I anticipate retiring in <10 years, and I feel that treatments with significantly higher cure rates will be available before then.

I wish you the very best,

John Tavis, PhD

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Thank John for such a quick response. I am optimistic about your message. My specialist Doctor checks on me once a year, I do lab and Ultrasound every six months. I read some posts ask for the drug price; since I am not tolerant of generic Entecavir well, I take Baraclude name brand. It cost me $100 a month with insurance and drug coverage. If I don’t have insurance, it will cost the US $1,200 a month.(who can afford this ??) I have to call a Specialty pharmacy to get a bottle of 30 pills every month.

thank you again,
Jo

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Hi Jo, this is Joan. I’m 62 years old and Korean American. So we have a lot in common! I was diagnosed 30 years ago and have been fortunate to live a relatively healthy life without any major complications. When I was 45 my liver specialist told me that I had to start antiviral therapy because my ALT levels were going up too high and she was worried. Anyhow, I’ve been on several different drugs - lamivudine (Epivir-HBV), tenofovir (Viread) and now TAF (Vemlidy). Just wondering whether your doctor would consider putting you on Viread or Vemlidy? Neither of these drugs require the food restrictions that come with Baraclude. Just a thought.

And as Dr. Tavis says above (he is a world-leading HBV scientist so he speaks of what he knows!), the hope is that new drugs in the pipeline show a lot of promise in delivering what is being called a “functional cure” in that folks like us wouldn’t have to take a drug forever! The new drugs being researched would be taken for a limited duration (one year or less) and result in suppressing the virus and reducing our risk of progressing to liver cancer. A “complete cure” is when the entire virus (think HBV viral cccDNA if you’ve heard of that) is eliminated from the infected liver cells. With a functional cure, the cccDNA is still lurking, but viral replication is so muted that the risks are significantly reduced.

Anyhow, welcome to the forum and all of us hope to hear more from you. I’m particularly excited because most of the time I feel like the token “grandma” on the forum!! Thanks again for joining the conversation, Joan

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Hi Joan, we do have a lot of commons. I am a Chinese American. I consider myself is very healthy and fit. I started the treatment when I was 52 after a severe bronchitis infection. Before that, I was considered an “inactive” carrier. During 2 months of steroid and inhaler treatments for bronchitis, my Hep B status change from inactive to extremely active. My alt triple and DNA were in the millions count, and I was referred to a GI doctor. I expected my Hep B to change so much was because of the drug induction. I did not want to get the treatment then. However, after a 6-month monitor, the DNA went to billions, and alt stayed high; that’s why I decide to get treatment. Three months after I started the Baraclue(Entecavir) , my alt drop and DNA became underactive, and it was maintained that status for the next four years. I consulted another doctor to see if I could stop the treatment in year 4. And yes, I did stop one year without any treatment. I ate healthy food and did exercise regularly. Unfortunately, this experiment did not reach my expectation. My alt number rose inch by inch every month, and the DNA back to millions again. I was so depressed and back to the Baraclude ever since.
I am happy with the Baraclude so far and don’t want to change unless I develop drug resistance. take care,
Jo

Hi John,
I would like to ask your opinion about the trial of Johnson & Johnson and Arrowhead Pharmaceuticals/ JNJ the 3989/.
I have been involved in a clinical trial of Arrowhead in 2016 but unfortunately excipient gave a side effect and the trial was stop. Now I see again Arrowhead into the new venture with promising outcome. Do you know anything about this trial and any forecast. Any other promising trial ?
Thank you

Liliana

Hi Joan,
I know that you have profound knowledge for the Hep B infection.
I am trying to find some articles to read and understand the progression of disease after certain time. I have red somewhere/ I cannot recall the article/ that in patients around 50’s the immune response is changing and some percentage of patients who were ‘‘inactive carriers’’ turn the disease to active again. If you can help me find some articles to read or comment on this also would be very valuable.
Thank you.
Lili

Dear Lili,

The most recent JNJ3989 trial has not been formally published yet that I know of, but an abstract is available (although is is hard to find and get access to). This link has a description of the results and is much more accessible: https://www.fiercebiotech.com/biotech/j-j-s-rnai-suppresses-hepatitis-b-for-48-weeks-after-last-dose

I do not know if the formulation issue that led to your problem has been solved. I suspect it has, but I do not know this for sure.

The easiest place I know of to find overview info on the state of drug development for HBV is the HBF Drug Watch page: https://www.hepb.org/treatment-and-management/drug-watch/

They also maintain a website about clinical trials: https://www.hepb.org/treatment-and-management/clinical-trials/

Hope this helps.

John

Dear John,
Thank you very much for providing me with this articles.
They are very interesting. I will serach in the links for new information.
I see big completion now between the J&J/Arrowhead and Roche/Dicerna.
I really hope one of those 2 will show promising results.

BR

Lili

Hi Lili, thanks for your messages that ask good questions. It’s wonderful that Dr. Tavis can share his scientific knowledge (as a leader in the field) with you and the rest of us. I will have to do a bit of searching to find some articles addressing the question that you asked about aging and hep B disease progression. There are lots of medical and scientific articles I’ve read over the years, but I’m not sure where they are anymore!! But yes, you’re right, as one gets older their hep B infection can become more “active” and we are at increased risk of progressing to cirrhosis and/or liver cancer. The unfortunate thing with chronic hep B is that we don’t necessarily have to develop cirrhosis BEFORE developing liver cancer. In contrast to hepatitis C infections where patients almost always develop cirrhosis before liver cancer (so there’s more warning). With that said, we’re not all going to develop liver cancer, but it’s a reason that we all need to be monitored regularly! At least once a year; ideally, every 6 months if one has the insurance (and frankly the time). Let me get back to you and hopefully others on the forum might have some good papers to share as well (calling Dr. Thomas Tu!!). Always, Joan

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Dear Joan,
Thank you very much for your kind and prompt response. We have to find a inner peace and accept the disease and leave with it. I have also noticed that daily low grade stress it is not good for the liver. So we need to find a perfect world in order to be able to leave normal life. Keep safe:)

Cure within 10 years? Seems great news! May I ask what are the names of the most promising researching programs?

Please remember that it is impossible to predict the pace of scientific advances, so “10 years” is an informed estimate, and nothing more. It is based on my synthesis of the very broad number of novel approaches being tried, the redundant efforts within most of the different approaches, the typical rate of drug development, and the wide-spread understanding that combinations of drugs will be needed to provide the functional cure that is so badly needed. I also strongly suspect that there will be no “one-size-fits-all” functional cure regimen. HBV is too genetically diverse and its disease presentation is so varied among chronically infected people, so I think there will be many drug combinations that need to be personalized to the individual patients. A complication for developing combinations is that the drugs have to be proven safe and at least somewhat effective by themselves prior to being tested in combination, and that adds time and complexity to the clinical trials.

With that context, the classes of compounds that are performing very well in development now include:

  1. Capsid assembly modifiers. There are a large number of molecules in clinical and preclinical development that are looking pretty good. The biggest issues at this point seem to be that resistance develops fairly easily to them, but that should be readily manageable with combination therapy.
  2. siRNAs. These are looking good in the clinic and are based on very solid basic science. They can be readily “tuned” to deal with genetic differences between HBV genotypes and resistance variants.
  3. Entry inhibitors. The lead molecule is Myrcludex B (now called Bulevirtide). It has been approved against HDV in Europe and should work against HBV because HBV and HDV enter cells the same way.
  4. Immune stimulators. These hold great promise for a functional cure because the immune system can clear HBV during an accute infection. However, the current generations of them are not as promising as I’d hoped, probably because the human immune system is incredibly complex.

For details on current drug development, please see the Hepatitis B Foundation Drug Watch page: https://www.hepb.org/treatment-and-management/drug-watch/

I hope this helps.

John

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This is great information! Thank you!

Thanks for the info, very helpful !

Food restrictions? I’m on Entercavir. Can you please explain.

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Hi Caraline, my understanding about entecavir is that you must take the pill on an empty stomach to help increase absorption of the drug. That means you should take entecavir 2 hours before or 2 hours after any meal, unless your doctor tells you otherwise. So to be clear, there are no “food restrictions” associated with entecavir. The key is to take it on an empty stomach. I hope this helps. Always, Joan

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