NurdRage finally got Pyrimethamine from household chemicals

[DrDu]

I wanted to bring to your attention what I think this is one of the most ambitious chemistry projects to be found on youtube:

A guy with the pseudonym of NurdRage or Dr. Butyllithium tried to synthesise a medication called Pyrimethamine or Daraprim which is effective against Toxoplasmosis from household products.
Although it has been known since the fifties and cost only some cents in many parts of the world, in the US the price was risen from 13 to 750 Dollars per pill in 2015, see
https://en.wikipedia.org/wiki/Pyrimethamine

This project took about two years and all the videos are highly worth watching.
I think it is a wonderful example as how even with very limited means, partly amateur equipment and resources, great science can be done.

 

[Ygggdrasil]

High school students in Australia also showed they could synthesize pyrimethamine for about $2 per pill:

Last fall, the biotech executive Martin Shkreli became widely reviled for hiking the price of a life-saving drug by more than 4,000 percent overnight, to $750 per pill.

Public outrage at Shkreli has apparently reverberated all the way to a high school science lab in Australia, where a group of 11th grade students claim to have proven a point: the drug can be made for much, much cheaper.

The group of 11 high school students, ages 16 and 17, successfully recreated the drug, Daraprim, for a mere $2 a pill, according to scientists from the University of Sydney.

https://www.washingtonpost.com/news...rice-hiked-pill-for-2/?utm_term=.d30d8616503d

Still, very impressive to synthesize the drug from household materials. Is there any summary of the entire synthetic scheme available?

 

[DrDu]

Yes, I know of the high school students. It is not difficult to synthesize the substance from commercially available precursors. What I found amazing was more the fact that you can do it in principle form household materials. This includes the synthesis of metallic sodium, chloroform, dioxane etc. At the end of the video I linked to, he shows a scheme of all the reactions.

 

[berkeman]

So I get that the company that owns the patent did a really bad thing by jacking the price so high like that in the US. But does posting a video about how to get around the patent have any legal issues? Just thinking of PF liability here...

 

[DrDu]

I understood that the patent expired long ago.

 

[berkeman]

I understood that the patent expired long ago.

Then how could the company jack up the price so high? If the patent protection had expired, their competition from generics would prevent that, no?

http://www.daraprimdirect.com/

https://en.wikipedia.org/wiki/Pyrimethamine

From Wikipedia:

Nobel Prize-winning American scientist Gertrude Elion developed the drug at Burroughs-Wellcome (now part of GlaxoSmithKline) to combat malaria.[20] Pyrimethamine has been available since 1953.[21] In 2010, GlaxoSmithKline sold the marketing rights for Daraprim to CorePharma. Impax Laboratories sought to buy CorePharma in 2014, and completed the acquisition, including Daraprim, in March 2015.[22] In August 2015, the rights were bought by Turing Pharmaceuticals.[23] Turing subsequently became known for a price hike controversy when it raised the price of a dose of the drug in the U.S. market from US$13.50 to US$750, a 5,500% increase.[24]

 

[TeethWhitener]

Then how could the company jack up the price so high? If the patent protection had expired, their competition from generics would prevent that, no?

From my understanding, in the US, in order to get FDA approval for a generic, it has to be tested and shown to be as effective as the name brand (even if it's the exact same molecule). But the companies selling the name brand can refuse to cooperate with companies wishing to get FDA approval for a competing generic. From the same wikipedia article:

...a closed distribution system could prevent generic competitors from legally obtaining the drugs for the bioequivalence studies required for FDA approval of a generic drug.

 

[Ygggdrasil]

So I get that the company that owns the patent did a really bad thing by jacking the price so high like that in the US. But does posting a video about how to get around the patent have any legal issues? Just thinking of PF liability here...

When a company patents a drug, it publicly discloses the methods for its synthesis (the whole point of the patent) in exchange for a limited period of market exclusivity. During that period, companies cannot use or sell the drug for the applications covered under the patent, but use of the compound in research and development is permitted (e.g. so that generic manufacturers can begin setting up processes to manufacture the drug so that the processes are ready for when the patent expires). Even if the drug were under patent, what NurdRage is doing is completely legal.

Then how could the company jack up the price so high? If the patent protection had expired, their competition from generics would prevent that, no?

The FDA has a variety of programs available for companies to take old drugs (like Daraprim) and bring them under modern regulatory frameworks. In exchange for doing this, the FDA will grant these companies a limited period of market exclusivity. Companies have taken advantage of these regulatory frameworks many times in the past (see http://blogs.sciencemag.org/pipeline/archives/2015/04/27/market_exclusivity_is_sometimes_too_much and http://blogs.sciencemag.org/pipelin...martin-shkreli-has-one-idea-and-its-a-bad-one).

in recent years, another strategy has emerged, and Retrophin/Turing are just the most dramatic examples of it. Entire companies have sprung up to take advantage of this sort of leverage – not by discovering their own drugs (too expensive, too risky!) but by buying up existing ones. And the most egregious examples have come in the generic sector. By various means, old generic compounds have ended up as protected species, and several companies have made it their business to take advantage of these situations to the maximum extent possible. The FDA grants market exclusivity to companies that are willing to take “grandfathered” compounds into compliance with their current regulatory framework, and that’s led to some ridiculous situations with drugs like colchicine and progesterone. (Perhaps the worst example is a company that’s using this technique to get ahold of a drug that’s currently being provided at no charge whatsoever). There are also loopholes that companies are trying to exploit when competitors try to prove generic equivalence: whatever it takes to keep competition away and get unlimited pricing power.

Companies have also taken advantage of orphan drug laws at the FDA to extend patents on their drugs and similarly prevent competition from generics (http://www.npr.org/sections/health-...seases-have-become-uncommonly-rich-monopolies).

a Kaiser Health News investigation shows that the system intended to help desperate patients is being manipulated by drugmakers to maximize profits and to protect niche markets for medicines already being taken by millions. The companies aren't breaking the law but they are using the Orphan Drug Act to their advantage in ways that its architects say they didn't foresee or intend. Today, many orphan medicines, originally developed to treat diseases affecting fewer than 200,000 people, come with astronomical price tags.

And many drugs that now have orphan status aren't entirely new. More than 70 were drugs first approved by the Food and Drug Administration for mass market use. These medicines, some with familiar brand names, were later approved as orphans. In each case, their manufacturers received millions of dollars in government incentives plus seven years of exclusive rights to treat that rare disease, or a monopoly.

What Shkreli did with Daraprim was just so egregious, people actually noticed, but it is by no means an outlier in pharma.