Chloramphenicol as intervention in heart attacks

post by G Gordon Worley III (gworley3) · 2020-02-17T18:47:44.328Z · EA · GW · 5 comments

This is a link post for

If the claims of this post are true, this could be an interesting target of EA effort and funding. Assuming the $25 million figure for approval is true, guessing at a $5 million cost for additional overhead for the life of the project, and estimating an average of 20 counterfactual additional QALYs generated per application of the therapy, that's $30 mm / (400k * 20) = $3.75 per QALY (assuming only applied for one year; cheaper per each year the intervention is used). Valuing a QALY at $50,000, that's a discount of 99.9925% per QALY and a payback period of approximately 600 patients.

Chloramphenicol is an antibiotic used mainly to treat eye infections, though it was originally developed 70 years ago to treat bubonic plague. Chloramphenicol is an ancient medicine, its patent long ago expired. Any generic drug company can make it in any country. Overseas it costs under $2 per dose ($40+ in America — why is that?).

When administered in a large intravenous dose within a couple hours of a heart attack, Chloramphenicol seems to prevent the heart muscle from being damaged. The mechanism by which Chloramphenicol works still isn’t well understood, but it seems to bump the heart into autophagy, which is a condition where the heart muscle cells eat their own cellular garbage for energy, thus avoiding damage. Autophagy is the direct physical benefit of fasting, in this case, imposed on the heart, thus saving it.

Every hospital, every emergency room, every EMT and ambulance should have a big dose of Chloramphenicol ready for those 800,000 heart attack victims per year. Doing so would not only save 400,000 lives per year, it would send 400,000 people back to whatever it was they were doing before their heart attack.

Emergency treatment is not a substitute for treating coronary artery disease, but it would save lives and allow second chances.

Published a decade ago, these facts have saved no lives. Four million Americans have died who didn’t have to die.

Four million Americans died because Chloramphenicol is off-patent so no drug company will touch it.

Chloramphenicol is an approved drug, but not approved for this purpose. Approving Chloramphenicol as a coronary treatment requires human trials that will probably cost $25 million.

That’s $25 million spent once to save 400,000 lives per year in the U.S. alone.

Such an expense would be a no-brainer for Big Pharma if they could somehow re-patent Chloramphenicol for this new purpose and charge $1000 per dose ($800 million per year) for a medicine that costs essentially nothing to produce.

But that’s not how patents work, so no company or government has been willing to fund human trials.


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comment by AviNorowitz (AviN) · 2020-02-18T05:07:08.700Z · EA(p) · GW(p)

This seems to be based on one study of 21 pigs.

Replies from: aarongertler
comment by Aaron Gertler (aarongertler) · 2020-02-20T02:27:58.788Z · EA(p) · GW(p)

I wish that the post had been more clear about this. It could still be promising to put together a human trial, of course, but success is far from certain.

comment by Aaron Gertler (aarongertler) · 2020-02-20T02:31:30.455Z · EA(p) · GW(p)

On the "20 QALY per application" figure, I have some questions:

  • What fraction of heart attack patients, if saved in this way, will not have another lethal heart attack within the next few years? 
  • What fraction of such patients are already very old and suffering from other health problems? 
  • To what extent might a nonlethal heart attack still lead to vulnerability and muscle weakness later on, making someone more susceptible to death?

I wouldn't be surprised if the true number were more like 2 QALY/application rather than 20 (still not a bad thing to try at that point if you think the other numbers fit; just wanted to call out this particular issue).

Replies from: gworley3
comment by G Gordon Worley III (gworley3) · 2020-02-20T22:26:47.447Z · EA(p) · GW(p)

Sure, this was just me taking a guess because I needed a figure to work out the numbers. I expect better analysis, if this is of interest to someone, might produce a different figure and different conclusion about cost effectiveness.

comment by cole_haus · 2020-02-19T01:28:18.846Z · EA(p) · GW(p)

Chloramphenicol is an approved drug, but not approved for this purpose. Approving Chloramphenicol as a coronary treatment requires human trials that will probably cost $25 million.

I am extremely far from an expert here so there may be some subtlety, but off-label uses are generally possible. From Wikipedia:

However, once a drug has been approved for sale for one purpose, physicians are free to prescribe it for any other purpose that in their professional judgment is both safe and effective, and are not limited to official, FDA-approved indications. This off-label prescribing is most commonly done with older, generic medications that have found new uses but have not had the formal (and often costly) applications and studies required by the FDA to formally approve the drug for these new indications.

Edit: The full post at the link acknowledges this:

As an approved drug (though for another purpose) any doctor can prescribe Chloramphenicol for any purpose. Of course, they don’t know to do this. And — perhaps more importantly — such bold action can get American doctors sued for malpractice.