6 ms·

Scientists Discover a Cure for the Deadliest Strain of Tuberculosis

511 points by rafaelc 7y ago

The_rationalist 7y ago
Firstly Ebola then tuberculosis, this week has been fascinating in the medecine world!
- deleted 7y ago
  [deleted]
- acrossthepond10 7y ago
  There was also a Chlamydia breakthrough. Good week indeed!
  - toomuchtodo 7y ago
    Was this separate from the Chlamydia vaccination passing a safety trial? https://www.theguardian.com/society/2019/aug/12/chlamydia-vaccine-clinical-trial-cure-sexually-transmitted-infection https://www.theguardian.com/society/2019/aug/12/chlamydia-va...
    - acrossthepond10 7y ago
      Nope. Thats the one. I guess less of a breakthrough and more of a promising step towards a treatment!
  - JetBen 7y ago
    That's absolutely amazing. According to my GP, there is a LOT of it here in Melbourne, Australia. Many of the strains are becoming antibiotic-resistant, so this is quite big news!
classichasclass 7y ago
I'm treating an XDR-TB patient right now (fortunately doing well). Too bad this wasn't there when we started.
- _asummers 7y ago
  What would be the ramifications of switching from current treatment to the new one midway through the current treatment?
  - mc32 7y ago
    I think they mean started in terms of treating patients with TB, as a physician rather than this particular patient? But maybe you’re right in which case I’d guess they’d be out cured much sooner.
  - classichasclass 7y ago
    Well, I don't have a supplier for this medication currently, and a study size of 109 is not large. The results are very promising but with TB, only certain medications work in certain combinations and you don't get to find out if you treated it wrong until sometimes years later when they relapse. If this particular patient asks about this study, and I won't be at all surprised if they do because this is a major article in a major paper and they're pretty well informed about their condition, I would probably tell them that while it looks very compelling I don't want to do this incorrectly and right now the best evidence is the WHO guideline as currently followed. Without going into detail, this patient is already on two of the three meds as it is.
- throwaway5752 7y ago
  Great news. I have not followed this, can you tell if it looks like this be any less susceptible resistance development?
  - classichasclass 7y ago
    Couldn't say definitively, but given that the biggest risks for resistance are monotherapy and intermittent therapy, shorter, less complex courses help to reduce the effective occurrence of both. Currently my MDR and XDR patients have about an 18+ month time frame; slashing the treatment time potentially to a third is a huge win, and we have robust directly-observed therapy infrastructure to ensure doses are actually taken. Unfortunately this last is not guaranteed in the developing world.
throwaway5752 7y ago
https://www.nature.com/articles/d41586-019-02464-0 https://www.nature.com/articles/d41586-019-02464-0 is the Nature article for those that don't want to bother getting passed the NYT's registration. It's not a drug discovery, it's an FDA approval of a 3 drug combination treatment of existing molecules. It's not a more deadly strain of tuberculosis, per se (to clarify: as in "more virulent", like H5N1 is compared to normally circulating strains of influenza), but it's the "XDR" designation. This is regular tuberculosis that has developed drug resistance to the prior final lines of treatments. edit: pretomanid is the newest and most novel of the 3 drug treatment. The FDA release is useful: https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-resistant-forms-tuberculosis-affects-lungs https://www.fda.gov/news-events/press-announcements/fda-appr...
- not_a_cop75 7y ago
  True, but the article says deadliest, not deadly. If my sister is the deadliest she's ever been, that doesn't mean she's going to kill me or even that she's even going to try. She might simply be more angry than ever before, and so the likelihood of killing me while still extremely low is higher than previous. Clickbaity, yes. Accurate, hard to say.
  - nocman 7y ago
    I think it is fair to say that using the term "deadliest" in this context gives almost everyone the impression that this strain of the disease is indeed deadly (that is to say, that a fair number of people die from it). So if very few people die from this strain (and I don't know the answer to that, but the grandparent comment implies that very few do), then I'd say it is definitely not accurate.
    - UnFleshedOne 7y ago
      Tb in general is surprisingly deadly actually. [0] "The World Health Organization estimates that 1.8 billion people—close to one quarter of the world's population—are infected with Mycobacterium tuberculosis (M.tb), the bacteria that causes TB. Last year, 10 million fell ill from TB and 1.6 million died." ... "There is growing resistance to available drugs, which means the disease is becoming more deadly and difficult to treat. There were 558,000 cases of drug resistant TB last year." [0] - https://www.tballiance.org/why-new-tb-drugs/global-pandemic https://www.tballiance.org/why-new-tb-drugs/global-pandemic EDIT: I say surprisingly, because before recently I was under impression that tb, being bacterial infection, was solved long ago.
nyasssh 7y ago
What about epimerox? Where is it? https://en.wikipedia.org/wiki/Epimerox https://en.wikipedia.org/wiki/Epimerox
ivanstame 7y ago
Scientists are on fire :)
zaroth 7y ago
Approved by the FDA today, this is a 3-drug cocktail which has shown a 90% cure rate against a highly deadly strain of TB called "XDR" (eXtensively Drug Resistant) in a small trail of 109 patients. It consists of pretomanid, bedaquiline, and linezolid, dosed daily for 6 months. Pretomanid was developed by the TB Alliance, and is targeted to be offered at a cost of $1 per dose. Back in 2000, apparently they raised about ~$150 million for drug development [1], I'm curious how much more they raised/spent since then to get to this point. Bedaquiline was developed by Janssen, it's not clear at what cost. They have a tiered pricing structure for a 6-month course ($900/$3,000/$30,000) but 3rd world cost has recently come down to $360. [2] Linezolid was developed by Pfizer, off patent since 2015. Pfizer doesn't seem to limit the cost in South Africa to any reasonable extent, charging between $60 - $150 per dose depending on who is buying it. However at least generics have come online in pill form for ~$7/dose [3] It sure would be nice if the development costs from Janssen and Pfizer were public, since it makes it basically impossible to compare, but the development model for pretomanid, and the innovative funding of the trials through TB Alliance to me demonstrates -- at least for diseases which are prevalent enough to build these alliances and obtain the donations -- a truly superior approach to providing treatment options for the world at prices that the world can afford. Congratulations to everyone involved for reaching such an impressive outcome, and particularly for doing it in an ethically responsible and economical approach. XDR TB is not currently extremely prevalent (seems like < 5% of all TB, but growing), but this is the first new TB drug approved in apparently in 40 years, and changes a 60% fatal diagnosis into a 90% curable disease, with a much simpler treatment protocol. [1] - https://www.tballiance.org/news/public-private-partnership-attacks-tuberculosis-aim-spur-development-new-drugs https://www.tballiance.org/news/public-private-partnership-a... [2] - http://www.treatmentactiongroup.org/sites/default/files/reality_check_bedaquiline_10_16_18.pdf http://www.treatmentactiongroup.org/sites/default/files/real... [3] - http://www.treatmentactiongroup.org/tb/linezolid-factsheet http://www.treatmentactiongroup.org/tb/linezolid-factsheet
nimz 7y ago
This advancement is especially promising because access to Delamanid (a drug similar to Pretomanid) is very difficult for patients in many countries. The company that developed Delamanid, Otsuka Pharmaceutical, has been extremely restrictive in allowing access to it. I know someone critically ill who was petitioning Otsuka for access to Delamanid under compassionate use, but Otsuka would only agree to give access if the patient stayed in a hospital for 4-6 months. This is just a crafty way for pharma companies to refuse access since they know the cost of months of hospital stay is not affordable or practical. Luckily in this instance, TB Alliance and others fought with Otsuka to get this patient access to the drug. In many high-need countries (India/Africa/China etc), desperate doctors frequently just lie to Otsuka about the patient staying in the hospital in order to get access to the drug. Opening access to Pretomanid is a great advancement!
- mkl 7y ago
  Why do they want extended hospital stays? Is it to boost their success statistics or something?
  - gdy 7y ago
    To make sure TB is cured and avoid developing a new drug-resistant strain?
  - nimz 7y ago
    The reason is that in some trials of Delamanid, a rare but serious side effect called QT prolongation was uncovered. To monitor for this side effect, a patient needs to have regular EKGs done. Since Delamanid is not approved in many countries yet (including the US), Otsuka wants to eliminate even the smallest chance of a patient complication which could delay their approval process. So they call for full hospitalization while the patient is on the drug. For brand new drugs that cure critical illnesses, the FDA has a compassionate use program (officially called Expanded Access) which allows drugs that are not fully approved yet to be used immediately by very ill patients. Otsuka requiring months of hospitalization to monitor for a rare side effect was just wrong and against the spirit of compassionate use access IMO. This side-effect is easily and cheaply monitored by regular EKGs at a local primary care doctor or urgent care clinic.
neonate 7y ago
http://archive.is/hOvd7 http://archive.is/hOvd7
sajan45 7y ago
I had a normal TB 3 years back. I was 22 years then. I have forgotten the drug names I took but it was 6 pills per day to be taken at morning with only half glass of water. I took that for 6 months. I am from India so not sure if any advanced country treats normal TB with less number of pills. But what I can say is that taking those pills in daily in empty stomach was unbearable, many times I thought to giveup but the love for my family kept me going. I can't imagine what those people are going through who are taking 40 pills a day. If FDA approved Pretomanid then in my opinion they should take more people into the trial.
- nimz 7y ago
  You must have taken the standard RIPE therapy which consists of 4 powerful drugs: rifampin, isoniazid, pyrazinamide, and ethambutol. Plus sometimes doctors add some other pills to control specific side effects a patient may be having like nausea or dizziness. I really appreciate you adding your personal perspective. A big problem in TB today is that the “western” world sees it mostly as a “not-my-problem” kind of disease. What people forget is that TB is airborne and that the world is getting smaller. It will start impacting everyone. TB is everyone’s problem and more investment should be made by the wealthier countries toward it’s care.
hi41 7y ago
This comes as a great news to many developing countries where doctors are worried about TB strains which are difficult to cure. TB carries with it the potential for great damage to lungs. People who suffer from TB have severely diminished breathing capacity and for many the 5 year prognosis is not good.

511 points by rafaelc 7y ago

The_rationalist 7y ago

Firstly Ebola then tuberculosis, this week has been fascinating in the medecine world!

deleted 7y ago
[deleted]
acrossthepond10 7y ago
There was also a Chlamydia breakthrough. Good week indeed!
- toomuchtodo 7y ago
  Was this separate from the Chlamydia vaccination passing a safety trial? https://www.theguardian.com/society/2019/aug/12/chlamydia-vaccine-clinical-trial-cure-sexually-transmitted-infection https://www.theguardian.com/society/2019/aug/12/chlamydia-va...
  - acrossthepond10 7y ago
    Nope. Thats the one. I guess less of a breakthrough and more of a promising step towards a treatment!
- JetBen 7y ago
  That's absolutely amazing. According to my GP, there is a LOT of it here in Melbourne, Australia. Many of the strains are becoming antibiotic-resistant, so this is quite big news!

classichasclass 7y ago

I'm treating an XDR-TB patient right now (fortunately doing well). Too bad this wasn't there when we started.

_asummers 7y ago
What would be the ramifications of switching from current treatment to the new one midway through the current treatment?
- mc32 7y ago
  I think they mean started in terms of treating patients with TB, as a physician rather than this particular patient? But maybe you’re right in which case I’d guess they’d be out cured much sooner.
- classichasclass 7y ago
  Well, I don't have a supplier for this medication currently, and a study size of 109 is not large. The results are very promising but with TB, only certain medications work in certain combinations and you don't get to find out if you treated it wrong until sometimes years later when they relapse. If this particular patient asks about this study, and I won't be at all surprised if they do because this is a major article in a major paper and they're pretty well informed about their condition, I would probably tell them that while it looks very compelling I don't want to do this incorrectly and right now the best evidence is the WHO guideline as currently followed. Without going into detail, this patient is already on two of the three meds as it is.
throwaway5752 7y ago
Great news. I have not followed this, can you tell if it looks like this be any less susceptible resistance development?
- classichasclass 7y ago
  Couldn't say definitively, but given that the biggest risks for resistance are monotherapy and intermittent therapy, shorter, less complex courses help to reduce the effective occurrence of both. Currently my MDR and XDR patients have about an 18+ month time frame; slashing the treatment time potentially to a third is a huge win, and we have robust directly-observed therapy infrastructure to ensure doses are actually taken. Unfortunately this last is not guaranteed in the developing world.

throwaway5752 7y ago

https://www.nature.com/articles/d41586-019-02464-0 https://www.nature.com/articles/d41586-019-02464-0 is the Nature article for those that don't want to bother getting passed the NYT's registration. It's not a drug discovery, it's an FDA approval of a 3 drug combination treatment of existing molecules. It's not a more deadly strain of tuberculosis, per se (to clarify: as in "more virulent", like H5N1 is compared to normally circulating strains of influenza), but it's the "XDR" designation. This is regular tuberculosis that has developed drug resistance to the prior final lines of treatments. edit: pretomanid is the newest and most novel of the 3 drug treatment. The FDA release is useful: https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-resistant-forms-tuberculosis-affects-lungs https://www.fda.gov/news-events/press-announcements/fda-appr...

not_a_cop75 7y ago
True, but the article says deadliest, not deadly. If my sister is the deadliest she's ever been, that doesn't mean she's going to kill me or even that she's even going to try. She might simply be more angry than ever before, and so the likelihood of killing me while still extremely low is higher than previous. Clickbaity, yes. Accurate, hard to say.
- nocman 7y ago
  I think it is fair to say that using the term "deadliest" in this context gives almost everyone the impression that this strain of the disease is indeed deadly (that is to say, that a fair number of people die from it). So if very few people die from this strain (and I don't know the answer to that, but the grandparent comment implies that very few do), then I'd say it is definitely not accurate.
  - UnFleshedOne 7y ago
    Tb in general is surprisingly deadly actually. [0] "The World Health Organization estimates that 1.8 billion people—close to one quarter of the world's population—are infected with Mycobacterium tuberculosis (M.tb), the bacteria that causes TB. Last year, 10 million fell ill from TB and 1.6 million died." ... "There is growing resistance to available drugs, which means the disease is becoming more deadly and difficult to treat. There were 558,000 cases of drug resistant TB last year." [0] - https://www.tballiance.org/why-new-tb-drugs/global-pandemic https://www.tballiance.org/why-new-tb-drugs/global-pandemic EDIT: I say surprisingly, because before recently I was under impression that tb, being bacterial infection, was solved long ago.

nyasssh 7y ago

What about epimerox? Where is it? https://en.wikipedia.org/wiki/Epimerox https://en.wikipedia.org/wiki/Epimerox

ivanstame 7y ago

Scientists are on fire :)

zaroth 7y ago

Approved by the FDA today, this is a 3-drug cocktail which has shown a 90% cure rate against a highly deadly strain of TB called "XDR" (eXtensively Drug Resistant) in a small trail of 109 patients. It consists of pretomanid, bedaquiline, and linezolid, dosed daily for 6 months. Pretomanid was developed by the TB Alliance, and is targeted to be offered at a cost of $1 per dose. Back in 2000, apparently they raised about ~$150 million for drug development [1], I'm curious how much more they raised/spent since then to get to this point. Bedaquiline was developed by Janssen, it's not clear at what cost. They have a tiered pricing structure for a 6-month course ($900/$3,000/$30,000) but 3rd world cost has recently come down to $360. [2] Linezolid was developed by Pfizer, off patent since 2015. Pfizer doesn't seem to limit the cost in South Africa to any reasonable extent, charging between $60 - $150 per dose depending on who is buying it. However at least generics have come online in pill form for ~$7/dose [3] It sure would be nice if the development costs from Janssen and Pfizer were public, since it makes it basically impossible to compare, but the development model for pretomanid, and the innovative funding of the trials through TB Alliance to me demonstrates -- at least for diseases which are prevalent enough to build these alliances and obtain the donations -- a truly superior approach to providing treatment options for the world at prices that the world can afford. Congratulations to everyone involved for reaching such an impressive outcome, and particularly for doing it in an ethically responsible and economical approach. XDR TB is not currently extremely prevalent (seems like < 5% of all TB, but growing), but this is the first new TB drug approved in apparently in 40 years, and changes a 60% fatal diagnosis into a 90% curable disease, with a much simpler treatment protocol. [1] - https://www.tballiance.org/news/public-private-partnership-attacks-tuberculosis-aim-spur-development-new-drugs https://www.tballiance.org/news/public-private-partnership-a... [2] - http://www.treatmentactiongroup.org/sites/default/files/reality_check_bedaquiline_10_16_18.pdf http://www.treatmentactiongroup.org/sites/default/files/real... [3] - http://www.treatmentactiongroup.org/tb/linezolid-factsheet http://www.treatmentactiongroup.org/tb/linezolid-factsheet

nimz 7y ago

This advancement is especially promising because access to Delamanid (a drug similar to Pretomanid) is very difficult for patients in many countries. The company that developed Delamanid, Otsuka Pharmaceutical, has been extremely restrictive in allowing access to it. I know someone critically ill who was petitioning Otsuka for access to Delamanid under compassionate use, but Otsuka would only agree to give access if the patient stayed in a hospital for 4-6 months. This is just a crafty way for pharma companies to refuse access since they know the cost of months of hospital stay is not affordable or practical. Luckily in this instance, TB Alliance and others fought with Otsuka to get this patient access to the drug. In many high-need countries (India/Africa/China etc), desperate doctors frequently just lie to Otsuka about the patient staying in the hospital in order to get access to the drug. Opening access to Pretomanid is a great advancement!

mkl 7y ago
Why do they want extended hospital stays? Is it to boost their success statistics or something?
- gdy 7y ago
  To make sure TB is cured and avoid developing a new drug-resistant strain?
- nimz 7y ago
  The reason is that in some trials of Delamanid, a rare but serious side effect called QT prolongation was uncovered. To monitor for this side effect, a patient needs to have regular EKGs done. Since Delamanid is not approved in many countries yet (including the US), Otsuka wants to eliminate even the smallest chance of a patient complication which could delay their approval process. So they call for full hospitalization while the patient is on the drug. For brand new drugs that cure critical illnesses, the FDA has a compassionate use program (officially called Expanded Access) which allows drugs that are not fully approved yet to be used immediately by very ill patients. Otsuka requiring months of hospitalization to monitor for a rare side effect was just wrong and against the spirit of compassionate use access IMO. This side-effect is easily and cheaply monitored by regular EKGs at a local primary care doctor or urgent care clinic.

neonate 7y ago

http://archive.is/hOvd7 http://archive.is/hOvd7

sajan45 7y ago

I had a normal TB 3 years back. I was 22 years then. I have forgotten the drug names I took but it was 6 pills per day to be taken at morning with only half glass of water. I took that for 6 months. I am from India so not sure if any advanced country treats normal TB with less number of pills. But what I can say is that taking those pills in daily in empty stomach was unbearable, many times I thought to giveup but the love for my family kept me going. I can't imagine what those people are going through who are taking 40 pills a day. If FDA approved Pretomanid then in my opinion they should take more people into the trial.

nimz 7y ago
You must have taken the standard RIPE therapy which consists of 4 powerful drugs: rifampin, isoniazid, pyrazinamide, and ethambutol. Plus sometimes doctors add some other pills to control specific side effects a patient may be having like nausea or dizziness. I really appreciate you adding your personal perspective. A big problem in TB today is that the “western” world sees it mostly as a “not-my-problem” kind of disease. What people forget is that TB is airborne and that the world is getting smaller. It will start impacting everyone. TB is everyone’s problem and more investment should be made by the wealthier countries toward it’s care.

hi41 7y ago

This comes as a great news to many developing countries where doctors are worried about TB strains which are difficult to cure. TB carries with it the potential for great damage to lungs. People who suffer from TB have severely diminished breathing capacity and for many the 5 year prognosis is not good.