6 ms·

New drug 'functionally cures' many hepatitis B virus infections

287 points by gmays 5mo ago

TZubiri 5mo ago
Are treated patients still contagious? If so, if a treated patient spreads the virus, will that new patient carry an innoculated virus? Or will they suffer a standard infection?
- Perenti 5mo ago
  I'm pretty sure that if the virus and its DNA are undetectable then you can't spread it. I believe that's how it works with HIV anyway.
  - deadmutex 5mo ago
    > if the virus and its DNA are undetectable then you can't spread it The devil may be in the details. E.g. if a COVID test shows negative, it doesn't mean that you can't spread it. This is partly because different tests have different sensitivities. > I'm pretty sure FYI, without citations, it is hard to distinguish credible experts vs people on the internet saying "trust me bro".
    - halapro 5mo ago
      Isn't half the selling point of antiretroviral therapy that you're no longer contagious? https://i-base.info/u-equals-u/ https://i-base.info/u-equals-u/ U=U probably does not apply to all diseases for the reasons you mentioned though.
  - abc123abc123 5mo ago
    Ahh, the classic corona fallacy. If you have something, X, which you cannot detect. Then you can count it as zero, since all you can do, is speculation not backed by any empirical evidence. If there is something you can detect and measure, then, we can start the great a mighty process of science.
    - OneDeuxTriSeiGo 5mo ago
      It's not really the same thing. If we exclusively tested coronavirus with PCR tests it'd be a lot more similar but the presence of kit tests and "30 minute covid testing" really muddied the water. And of course Covid tests are primarily mucous membrane based which is going to be inherently harder to evenly test compared to a blood sample where viral load is pretty evenly distributed. At least for blood based diseases, detecting viral load via PCR testing is to such a sensitivity that if there's essentially any active viruses out and about or any active viral RNA floating around in cells then the tests come back positive. And with sustained antiviral use testing is less about "do I have it/will I become contagious in the near future" (like coronavirus) and rather "is my antiviral regimen still killing the virus faster than it can wake up from latent genetic material sleeping in DNA". The former is a timing problem from one shot testing the latter is monitoring a steady state to track that the treatment remains effective and when it ceases being effective there's a lag time between viral load being detectable and sufficient viral load to be meaningfully contagious.
    - throwway120385 5mo ago
      It depends on why you're testing. You never just test to gather data without purpose. So when we were doing PCR testing, it was partly about gathering population statistics to build dashboards, because a surge in positive PCR test results would correlate to a subsequent surge in the hospitalization rate. The hospitalization rate and the percentage of empty versus full beds were what needed to be managed, as an increase in severe Covid patients would overwhelm hospitals making it impossible to treat people with otherwise routine emergencies like arterial wounds. There were a lot of videos out of India in late 2020 which showed the result of uncontrolled Covid surges, and it was mostly Hospital Full -> No treatment for anyone -> Lots of deaths. Or a lot of sick and injured people waiting outside or taking welding gas because the hospital grade oxygen was used up. By contrast, testing with rapid tests is mostly about seeing why you're sick before you go somewhere, and those tests probably don't need to be as sensitive. The hospital has capacity to treat people because of the PCR tests and so we can manage if some of the PCR tests are false-negative. Most people are vaccinated so we can tolerate some Covid-positive people mingling in public places now. Tests aren't magical, and there are different tests with different capabilities. I'd suggest you learn about sensitivity versus specificity and learn how to compute the false positive, false negative, true positive, and true negative rates. It might be eye opening for you.
- sleepyguy 5mo ago
  A patient that is functionally cured shouldn't pass on the disease. Since it is cleared from the blood and the viral DNA is undetectable, it is not replicating anymore, so it can't be transmitted. They risk is not absolute since the dormant virus is still genetically encoded in the liver.
- rustyhancock 5mo ago
  For now all one can say is transmission is assumed to be dramatically reduced. The bigger risk is likely that in some the suppression is temporary or transient flares of replication under some circumstances. The other question is, does this avoid all the sequela of HBV. It seems to reduce risk of cirrhosis atleast. For hiv, it took many decades to be able to make the clam undetectable = untransmittable using serodiscordant couple studies.
- altairprime 5mo ago
  (Meta note: This exposure scenario hinges on whether the second party has previously completed the HepB vaccine schedule. So, for those evaluating this risk equation, duly noted that a vaccine exists that the yet-uninfected party above could have received.)
- mariaerica 5mo ago
  [dead]
madanparas 5mo ago
[flagged]
- skissane 5mo ago
  > The 19% result is real and independently replicated in over 1,800 patients, but whether bepirovirsen reduces the 1.1 million HBV deaths per year depends on trials in populations that weren't enrolled here. Do we know, how many of those deaths are due to limitations of existing treatments, versus how many are due to health care access issues?
- cbg0 5mo ago
  This comment smells like Claude.
  - hackeman300 5mo ago
    Agreed. >AI Engineer @Varnan Labs Bingo. A glance at their comment history shows this is a pattern for them
amwet 5mo ago
Pretty sure the cover image is a Strokes album cover.
- burner420042 5mo ago
  Is This It My sister, who is two years younger, was in 8th or 9th grade when this album came out. She's also a Weezer and Radio Head fan. Only a few years difference but I feel this genre came after me.
- efields 5mo ago
  > For the American market and the October 2001 release, the cover art of Is This It was changed to a psychedelic photograph of subatomic particle tracks in a bubble chamber. https://en.wikipedia.org/wiki/Is_This_It https://en.wikipedia.org/wiki/Is_This_It
halapro 5mo ago
I'm surprised that they're working on HB cures since there's been an HB vaccine for 40 years. I'd love to see more work done towards other incurable viruses like HSV (no vaccine) and HPV (limited vaccine)
- tfourb 5mo ago
  There are > 800.000 yearly deaths due to hep b. https://en.wikipedia.org/wiki/Hepatitis_B https://en.wikipedia.org/wiki/Hepatitis_B Yes, there is an effective vaccine but not everyone has access to it for tons of reasons.
  - chimeracoder 5mo ago
    > Yes, there is an effective vaccine but not everyone has access to it for tons of reasons. Also, about 3.5% of the world's population already has it. That's about 300 million people for whom a vaccine is pointless, and who are at dramatically higher risk of liver cancer (somewhere between 15-50% lifetime risk of an extremely deadly type of cancer), and for whom a cure would literally be life-changing, if available.
- Centigonal 5mo ago
  Herpes viruses like HSV are notoriously difficult to target with medication bc they encode themselves into DNA inside the nuclei of long-lived human nerve cells. Between outbreaks, they basically exist only as rogue DNA floating inside mostly-healthy cells in the nerve ganglia. At some point, something triggers the nerve cell to transcribe the rogue DNA, producing new viruses and beginning a new outbreak.
  - mrtesthah 5mo ago
    IM-250 (Adibelivir) is a helicase-primase inhibitor that targets latent HSV so well it may actually permanently reduce the pool of viable latent HSV genomes.
    - shevy-java 5mo ago
GreenSalem 5mo ago
Indian pharmaceutical companies will produce a biosimilar in months. This will enable it to be supplied at a non-exploitative price to Africa and Asia.
- Zenst 5mo ago
  They produce drugs whose patents have expired; drugs still under patent are something they mostly avoid. The term for 3rd party versions of these drugs are often referred to as `generics`, which sees the same drug, but a different name(names also have copyrights that seem to extend longer). However, if they can tweak the drug and make it something that escapes the patent and still works then good for them and everyone else. Though mindful large pharma is rather tight and lawyer-heavy when it comes to protecting their IP. As of now it is under patent that expires in 2032, and also not FDA approved, so with how long that process takes, either way, wont see it available anytime soon in drug regulated countries. But grey imports/black market trade in pharma drugs is not to be overlooked.
  - singpolyma3 5mo ago
    > names also have copyrights Probably you're thinking of trademark. A name cannot have a copyright
- philipallstar 5mo ago
  > This will enable it to be supplied at a non-exploitative price to Africa and Asia. It's millions of times easier to copy than to discover. Discovery needs paying for, and the places that don't discover aren't owed things by places that do.
shevy-java 5mo ago
> “functionally cured” > 19% of people > naturally control that virus without any further treatments So in other words: a very minor result. 19% is not a lot. And the term "functionally cured" when they still have the virus, is not a cure, by definition. I get that for many this may be an improvement, but my gripe is with the wording here. This is inflation of feel-goodness.
- TheAceOfHearts 5mo ago
  It helps to look at some figures to bring it into perspective instead of making off hand comments about how it's not a lot. Remember these are human lives! After some searching, I found estimates ranging between 600 thousand to 1.6 million people living with Hepatitis B in the US. If we can help 20% of those people, that means significant life improvements to somewhere between 120 thousand and 320 thousand people. If we take the upper end, that's half the population of Wyoming.
  - 2muchcoffeeman 5mo ago
    Yes! Always run some numbers in your head. People will sometimes pick percentages or numbers in an attempt to bolster their arguments. Don’t buy it, work it out for yourself.
  - mlyle 5mo ago
    It is also worth noting that others were helped, too, just not to the extraordinary level of a functional cure.
- energy123 5mo ago
  19% vs 15% would be "not a lot". But this is 19% vs 0%! Quote: "233 of 1220 people who had received bepi had functional cures—both undetectable HBV DNA and surface antigen—versus zero of 614 participants in the placebo arm." This is a HUGE deal because low virality now doesn't mean low virality in the future.
hereme888 5mo ago
> "Like the nukes, bepi doesn’t eliminate the embedded cccDNA..." That's the ugly part about these rt-DNA viruses. They embed into your own DNA, causing issues for life.
- mariaerica 5mo ago
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mariaerica 5mo ago
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mariaerica 5mo ago
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mariaerica 4mo ago
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287 points by gmays 5mo ago

Are treated patients still contagious? If so, if a treated patient spreads the virus, will that new patient carry an innoculated virus? Or will they suffer a standard infection?

Perenti 5mo ago
I'm pretty sure that if the virus and its DNA are undetectable then you can't spread it. I believe that's how it works with HIV anyway.
- deadmutex 5mo ago
  > if the virus and its DNA are undetectable then you can't spread it The devil may be in the details. E.g. if a COVID test shows negative, it doesn't mean that you can't spread it. This is partly because different tests have different sensitivities. > I'm pretty sure FYI, without citations, it is hard to distinguish credible experts vs people on the internet saying "trust me bro".
  - halapro 5mo ago
    Isn't half the selling point of antiretroviral therapy that you're no longer contagious? https://i-base.info/u-equals-u/ https://i-base.info/u-equals-u/ U=U probably does not apply to all diseases for the reasons you mentioned though.
- abc123abc123 5mo ago
  Ahh, the classic corona fallacy. If you have something, X, which you cannot detect. Then you can count it as zero, since all you can do, is speculation not backed by any empirical evidence. If there is something you can detect and measure, then, we can start the great a mighty process of science.
  - OneDeuxTriSeiGo 5mo ago
    It's not really the same thing. If we exclusively tested coronavirus with PCR tests it'd be a lot more similar but the presence of kit tests and "30 minute covid testing" really muddied the water. And of course Covid tests are primarily mucous membrane based which is going to be inherently harder to evenly test compared to a blood sample where viral load is pretty evenly distributed. At least for blood based diseases, detecting viral load via PCR testing is to such a sensitivity that if there's essentially any active viruses out and about or any active viral RNA floating around in cells then the tests come back positive. And with sustained antiviral use testing is less about "do I have it/will I become contagious in the near future" (like coronavirus) and rather "is my antiviral regimen still killing the virus faster than it can wake up from latent genetic material sleeping in DNA". The former is a timing problem from one shot testing the latter is monitoring a steady state to track that the treatment remains effective and when it ceases being effective there's a lag time between viral load being detectable and sufficient viral load to be meaningfully contagious.
  - throwway120385 5mo ago
    It depends on why you're testing. You never just test to gather data without purpose. So when we were doing PCR testing, it was partly about gathering population statistics to build dashboards, because a surge in positive PCR test results would correlate to a subsequent surge in the hospitalization rate. The hospitalization rate and the percentage of empty versus full beds were what needed to be managed, as an increase in severe Covid patients would overwhelm hospitals making it impossible to treat people with otherwise routine emergencies like arterial wounds. There were a lot of videos out of India in late 2020 which showed the result of uncontrolled Covid surges, and it was mostly Hospital Full -> No treatment for anyone -> Lots of deaths. Or a lot of sick and injured people waiting outside or taking welding gas because the hospital grade oxygen was used up. By contrast, testing with rapid tests is mostly about seeing why you're sick before you go somewhere, and those tests probably don't need to be as sensitive. The hospital has capacity to treat people because of the PCR tests and so we can manage if some of the PCR tests are false-negative. Most people are vaccinated so we can tolerate some Covid-positive people mingling in public places now. Tests aren't magical, and there are different tests with different capabilities. I'd suggest you learn about sensitivity versus specificity and learn how to compute the false positive, false negative, true positive, and true negative rates. It might be eye opening for you.
sleepyguy 5mo ago
A patient that is functionally cured shouldn't pass on the disease. Since it is cleared from the blood and the viral DNA is undetectable, it is not replicating anymore, so it can't be transmitted. They risk is not absolute since the dormant virus is still genetically encoded in the liver.
rustyhancock 5mo ago
For now all one can say is transmission is assumed to be dramatically reduced. The bigger risk is likely that in some the suppression is temporary or transient flares of replication under some circumstances. The other question is, does this avoid all the sequela of HBV. It seems to reduce risk of cirrhosis atleast. For hiv, it took many decades to be able to make the clam undetectable = untransmittable using serodiscordant couple studies.
altairprime 5mo ago
(Meta note: This exposure scenario hinges on whether the second party has previously completed the HepB vaccine schedule. So, for those evaluating this risk equation, duly noted that a vaccine exists that the yet-uninfected party above could have received.)
mariaerica 5mo ago
[dead]

madanparas 5mo ago

[flagged]

skissane 5mo ago
> The 19% result is real and independently replicated in over 1,800 patients, but whether bepirovirsen reduces the 1.1 million HBV deaths per year depends on trials in populations that weren't enrolled here. Do we know, how many of those deaths are due to limitations of existing treatments, versus how many are due to health care access issues?
cbg0 5mo ago
This comment smells like Claude.
- hackeman300 5mo ago
  Agreed. >AI Engineer @Varnan Labs Bingo. A glance at their comment history shows this is a pattern for them

amwet 5mo ago

Pretty sure the cover image is a Strokes album cover.

burner420042 5mo ago
Is This It My sister, who is two years younger, was in 8th or 9th grade when this album came out. She's also a Weezer and Radio Head fan. Only a few years difference but I feel this genre came after me.
efields 5mo ago
> For the American market and the October 2001 release, the cover art of Is This It was changed to a psychedelic photograph of subatomic particle tracks in a bubble chamber. https://en.wikipedia.org/wiki/Is_This_It https://en.wikipedia.org/wiki/Is_This_It

halapro 5mo ago

I'm surprised that they're working on HB cures since there's been an HB vaccine for 40 years. I'd love to see more work done towards other incurable viruses like HSV (no vaccine) and HPV (limited vaccine)

tfourb 5mo ago
There are > 800.000 yearly deaths due to hep b. https://en.wikipedia.org/wiki/Hepatitis_B https://en.wikipedia.org/wiki/Hepatitis_B Yes, there is an effective vaccine but not everyone has access to it for tons of reasons.
- chimeracoder 5mo ago
  > Yes, there is an effective vaccine but not everyone has access to it for tons of reasons. Also, about 3.5% of the world's population already has it. That's about 300 million people for whom a vaccine is pointless, and who are at dramatically higher risk of liver cancer (somewhere between 15-50% lifetime risk of an extremely deadly type of cancer), and for whom a cure would literally be life-changing, if available.
Centigonal 5mo ago
Herpes viruses like HSV are notoriously difficult to target with medication bc they encode themselves into DNA inside the nuclei of long-lived human nerve cells. Between outbreaks, they basically exist only as rogue DNA floating inside mostly-healthy cells in the nerve ganglia. At some point, something triggers the nerve cell to transcribe the rogue DNA, producing new viruses and beginning a new outbreak.
- mrtesthah 5mo ago
  IM-250 (Adibelivir) is a helicase-primase inhibitor that targets latent HSV so well it may actually permanently reduce the pool of viable latent HSV genomes.
  - shevy-java 5mo ago

GreenSalem 5mo ago

Indian pharmaceutical companies will produce a biosimilar in months. This will enable it to be supplied at a non-exploitative price to Africa and Asia.

Zenst 5mo ago
They produce drugs whose patents have expired; drugs still under patent are something they mostly avoid. The term for 3rd party versions of these drugs are often referred to as `generics`, which sees the same drug, but a different name(names also have copyrights that seem to extend longer). However, if they can tweak the drug and make it something that escapes the patent and still works then good for them and everyone else. Though mindful large pharma is rather tight and lawyer-heavy when it comes to protecting their IP. As of now it is under patent that expires in 2032, and also not FDA approved, so with how long that process takes, either way, wont see it available anytime soon in drug regulated countries. But grey imports/black market trade in pharma drugs is not to be overlooked.
- singpolyma3 5mo ago
  > names also have copyrights Probably you're thinking of trademark. A name cannot have a copyright
philipallstar 5mo ago
> This will enable it to be supplied at a non-exploitative price to Africa and Asia. It's millions of times easier to copy than to discover. Discovery needs paying for, and the places that don't discover aren't owed things by places that do.

shevy-java 5mo ago

> “functionally cured” > 19% of people > naturally control that virus without any further treatments So in other words: a very minor result. 19% is not a lot. And the term "functionally cured" when they still have the virus, is not a cure, by definition. I get that for many this may be an improvement, but my gripe is with the wording here. This is inflation of feel-goodness.

TheAceOfHearts 5mo ago
It helps to look at some figures to bring it into perspective instead of making off hand comments about how it's not a lot. Remember these are human lives! After some searching, I found estimates ranging between 600 thousand to 1.6 million people living with Hepatitis B in the US. If we can help 20% of those people, that means significant life improvements to somewhere between 120 thousand and 320 thousand people. If we take the upper end, that's half the population of Wyoming.
- 2muchcoffeeman 5mo ago
  Yes! Always run some numbers in your head. People will sometimes pick percentages or numbers in an attempt to bolster their arguments. Don’t buy it, work it out for yourself.
- mlyle 5mo ago
  It is also worth noting that others were helped, too, just not to the extraordinary level of a functional cure.
energy123 5mo ago
19% vs 15% would be "not a lot". But this is 19% vs 0%! Quote: "233 of 1220 people who had received bepi had functional cures—both undetectable HBV DNA and surface antigen—versus zero of 614 participants in the placebo arm." This is a HUGE deal because low virality now doesn't mean low virality in the future.

hereme888 5mo ago

> "Like the nukes, bepi doesn’t eliminate the embedded cccDNA..." That's the ugly part about these rt-DNA viruses. They embed into your own DNA, causing issues for life.

mariaerica 5mo ago
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mariaerica 5mo ago

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mariaerica 5mo ago

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mariaerica 4mo ago

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