
Scientists Discover a Cure for the Deadliest Strain of Tuberculosis - rafaelc
https://www.nytimes.com/2019/08/14/health/tuberculosis-xdr-tb-cure.html
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nimz
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
Why do they want extended hospital stays? Is it to boost their success
statistics or something?

~~~
nimz
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.

~~~
refurb
Considering QT prolongation has resulted in several drugs being pulled off the
market, I’m not sure I blame the Pharma company for being cautious.

They are putting the use of the drug entirely in the hands of people who might
not have the resources or training needed. If the use of the drug resulted in
several deaths, it could significantly delay approval or kill the program
entirely.

~~~
nimz
True that they're being cautious to protect their investment in the drug. In
the case of TB, it's taken seriously enough that the drugs used to treat
MDR/XDR TB are taken under close medical supervision, especially brand new
drugs like Bedaquiline and Delamanid. They are usually administered under DOT
(directly observed therapy) where a patient is required by law to take the
drugs daily in front of a witness, or with lower-risk patients they use VDOT
(Video Directly Observed Therapy) where patients can use an app to video
record themselves taking the medicine daily and submit the evidence to the
local Department of Health. In cases where patients don't comply to treatment,
they can be arrested and isolated due to the public health risk.

~~~
refurb
Protecting their investment sure, but it can extend beyond that to impact
clinical perceptions of the drug such that it limits use unnecessarily
(regardless of whether Otsuka markets it).

I was tangentially involved in a clinical development program that offered
access through compassionate use. The folks who received the drug were truly
out of options. As a result several died. Investigation determine the drug was
not the cause. That didn’t stop the rumors from swirling and several
physicians pulling out of the clinical trials and actively discouraging
patients from taking part. Probably extended the development by at least 2
years (it was eventually approved) and as a result many people who could of
benefited from it had to wait, which likely resulted in a number of deaths
that could have been avoided.

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sajan45
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
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.

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throwaway5752
[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-
appr...](https://www.fda.gov/news-events/press-announcements/fda-approves-new-
drug-treatment-resistant-forms-tuberculosis-affects-lungs)

~~~
whiddershins
Hold on, before we get in to a confusing argument of terms, does this strain
of tuberculosis have one of highest mortality rates per infection or not?

If so, the headline is more or less accurate.

If not, please explain.

~~~
classichasclass
Apologies for the Elsevier link, but
[https://www.thelancet.com/journals/lanres/article/PIIS2213-2...](https://www.thelancet.com/journals/lanres/article/PIIS2213-2600\(17\)30079-6/fulltext)

The report estimates around 40% mortality for MDR-TB and 60% mortality for
XDR-TB.

This compares with
[https://www.who.int/gho/tb/epidemic/cases_deaths/en/](https://www.who.int/gho/tb/epidemic/cases_deaths/en/)
which gives about ~13% mortality for all TB cases world wide.

So, I think the headline is accurate about that. However, we could cure (at
least for some definition of "cure") XDR-TB before; it just took an incredible
amount of time with some terrible drugs and some individuals still relapsed.
Pa could be a game changer, though. I'll give it a "somewhat justifiably
clickbaity" rating. ;)

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zaroth
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-a...](https://www.tballiance.org/news/public-private-partnership-
attacks-tuberculosis-aim-spur-development-new-drugs)

[2] -
[http://www.treatmentactiongroup.org/sites/default/files/real...](http://www.treatmentactiongroup.org/sites/default/files/reality_check_bedaquiline_10_16_18.pdf)

[3] - [http://www.treatmentactiongroup.org/tb/linezolid-
factsheet](http://www.treatmentactiongroup.org/tb/linezolid-factsheet)

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

~~~
acrossthepond10
There was also a Chlamydia breakthrough. Good week indeed!

~~~
toomuchtodo
Was this separate from the Chlamydia vaccination passing a safety trial?

[https://www.theguardian.com/society/2019/aug/12/chlamydia-
va...](https://www.theguardian.com/society/2019/aug/12/chlamydia-vaccine-
clinical-trial-cure-sexually-transmitted-infection)

~~~
acrossthepond10
Nope. Thats the one. I guess less of a breakthrough and more of a promising
step towards a treatment!

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

~~~
_asummers
What would be the ramifications of switching from current treatment to the new
one midway through the current treatment?

~~~
classichasclass
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.

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nyasssh
What about epimerox? Where is it?
[https://en.wikipedia.org/wiki/Epimerox](https://en.wikipedia.org/wiki/Epimerox)

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hi41
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.

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neonate
[http://archive.is/hOvd7](http://archive.is/hOvd7)

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ivanstame
Scientists are on fire :)

