World’s Most EXPENSIVE Medicines: Greedy or Fair? What Makes them Special? (Gene Therapy, Chemistry)
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- Опубликовано: 5 июл 2024
- To try everything Brilliant has to offer-free-for a full 30 days, visit brilliant.org/TotalSynthesis/. The first 200 of you will get 20% off Brilliant’s annual premium subscription.
🤑 Imagine a single dose of medicine priced at $3.5 MILLION. Since the approval of the gene therapy Hemgenix , this is a reality. How can this be fair? Stay tuned to better understand the costs and risks of drug development, learn about the world's most expensive gene therapy and small molecule, and learn some new things about science.
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00:00 Absurdly expensive drugs - what you will learn today
01:20 Honorary mentions (Skysona, Zynteglo, Soliris)
02:57 Pharma business basics: R&D cost, peak sales, functional cost, gross-to-net, probability of success
05:13 Most expensive small molecule: An "ultra-ultra rare disease drug" (lonafarnib, Zokinvy)
08:45 Organic chemistry and process synthesis
11:05 Most expensive gene therapy: Hemgenix, hemophilia B, how gene therapies work
14:20 The best way to learn: Brilliant.org
15:32 How many sales Hemgenix might get - Explained
18:49 Recap and closing remarks
This video was sponsored by Brilliant.
Disclaimer - This channel does not provide medical advice!
No information on this channel is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of information on RUclips.
Key references:
- Lonafarnib: First Approval | Drugs. 2021; 81(2): 283
- A Novel Iodide-Catalyzed Reduction of Nitroarenes and Aryl Ketones with H3PO2 or H3PO3: Its Application to the Synthesis of a Potential Anticancer Agent | Org. Lett. 2011; 13 (19): 5220
- Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome | Circulation 2014;130(1): 27
- Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B | N Engl J Med
. 2023; 388(8): 706
- Etranacogene dezaparvovec for hemophilia B gene therapy | Therapeutic Advances in Rare Disease. 2021;2. doi: 10.1177/26330040211058896
- Structure-activity relationship study to improve cytotoxicity and selectivity of lonafarnib against breast cancer cells | Arch Pharm (Weinheim) 2023; 356(4): e2200263
- Deloitte | Measuring return from pharmaceutical innovation 2022
- IQVIA | Global Trends in R&D 2021
Some recommended books on organic synthesis:
- Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge)
- Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis)
- Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions)
- Nicolaou; Classics in Total Synthesis 1-3 (the ultimate total synthesis trilogy)
- Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life)
- Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures)
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Pharmaceutical industry, worlds most expensive drug, chemical synthesis, ultra-rare disease, Hemgenix, gene therapies, Skysona, Zynteglo, Institute for Clinical and Economic Review, cost-effectiveness analyses, Soliris, research & development costs, pharma R&D, peak sales, market model, selling and marketing, gross-to-net , US healthcare system, probability of success 
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▶ To try everything Brilliant has to offer-free-for a full 30 days, visit brilliant.org/TotalSynthesis/. The first 200 of you will get 20% off Brilliant’s annual premium subscription.
The answer to the chemistry question from Brilliant:
Assumptions - The added iridium is the same temperature as the steam/methane mixture, and the volume of the reactor tank is kept constant.
Answer - Adding Ir while keeping the reactor size and the added gases constant will lead to an increase in pressure in the reactor (because by adding a solid, we've effectively decreased the volume of the reactor). An increase in pressure will push the equilibrium point of the steam reformation reaction towards methane and steam, since that would reduce the number of gas molecules in the reactor, partially counteracting the increase in pressure. Adding Ir will therefore decrease the total amount of HX2 produced, even though it doesn't react with any of the other chemicals present.
No effect whatsoever, the Iridium would get stolen way before it ever reaches the reactor
Is it morally acceptable to make everyone pay $10M so someone else's kid can live to the ripe old age of 15, rather than 13?
In short, not really
@@totalsynthesisNot in the USA where your citizens pay. But here our corps pay all our taxes. You might wann try it so you stop whining about macroeconomics.
For some drugs I 100% understand the price, like if you're going to spend millions to develop a drug to cure a disease only 1 in 20 million people has, the price has to be high enough to justify its cost.
The only real solution in this situation would be the government covering part or all of the cost as I doubt an insurance company would ever pay for it.
Well having the government cover the cost is risky and could end up increasing the price of the drug. It's the same idea as colleges increasing tuition because of federally backed loans.
Governments are already pouring billions into medical research but the results still get privatized🤔
@@asadburden1621yes, but much like with university, congress has the power to price cap as either the funder or buyer and could easily do so
@@asadburden1621 What nonsense are you blabbling. this drug is free to citizens around the world. You Ametricans are subsidizing us because of fools like you who buy the Fox news propoganda. Thank you for that. Very much.
@@W333L Don't bother. Where I live nobody complains about the economy cuz none of us pay 1 cent for healthcare, your right-wingers just like to be victims to they can complain. They know literally nothing about anything first-hand, its all from their talking heads.
They really should’ve chosen a different name. It sounds a bit too close to “eugenics”
There's nothing wrong with eugenics
@@warrior7038 women do this literally every time they reject a guy
what does any of what you just said have to do with eugenics?@@AnthonyBolognese710
You got yourself a new sub. Damn I missed organic chemistry. I can’t believe I’m saying that, but as someone who majored in biochem and then went into another field, it takes me back. It’s still difficult for me to follow along but I enjoy the challenge.
Thank you! Glad you enjoy it
“Small molecule.” It’s weird how drugs are considered small up to 1500 daltons cuz that molecule looks pretty damn big to me
_smol_
Get smol hahaha. Great reply.
When you start with the assumption that there must be rent-seekers paid off at every stage of this process, of course these numbers can sometimes seem reasonable. Maybe re-examine that assumption instead of rimming plutes.
Exactly, the idea that healthcare should always drive a profit is the main thing wrong with this video
@@nicov6383 I know where you are coming from - that's how the capital-based world runs (not saying that this is my personal view/ preference, I'm just explaining status quo). I hope I could at least show why - even in the ideal scenario - it's impossible to sell some medicines below hundreds of thousands of dollars.
@@totalsynthesis I totally understand don’t worry, it just makes me incredibly sad that this is the case
It is always a pleasure to watch your videos. You bring an incredible amount of insight and brilliance to a topic that has so much controversy.
Thank you for the kind words!!
Martin skreli be like: write that down 😂
The Purdue's are too at this point...
He‘s back 🔥🔥🔥 Always getting excited when I see a new video of you popping up in my feed! Keep it up please :D
Glad to see you posting again, I really missed these :)
Thanks! At least monthly vids coming again :)
my treatment is 120k a treatment that is 8 times a year plus nursing. Unfortunately especially in the USA drugs are not price regulated. But it is disgusting that health has a price tag.
Depending on what drug you are using there are labs in china that don't care about patents that will make you a life time supply of said substance . Ofc if it's a complex molecule then you can buy them from India for probably 25% the price
If you don’t mind me asking, what’s your condition and what treatments/drugs do you use?
@@zorintoto1167 You'd likely need to send off whatever they send you to a lab to have it tested to make sure its exactly what you ordered but that would still be cheaper than 120k a treatment for a lifetime supply.
@@zorintoto1167 I take specialized chemotherapy and the drugs used have to be certified by the FDA or the Infusion people would not and legally unable to administer, I will agree other country's can and will sell different drugs at a much cheaper price.
Greed 100%
cant even get adhd medicine since 6/22 of last year.
Sorry to hear!
My cousin has hemophilia, but I'm not sure if it is the B variant. He is not technically a blood relative, as my uncle adopted him when he married his mother, so the gene isn't in my family tree. I know he had to be hospitalized several times as a child. However, he is 44 now and seems to be fairly healthy
Congratulations on the excellent video. It must have taken a lot of work to create and edit it. If I may have a suggestion, I would like you to comment on Tamiflu (Oseltamivir phosphate). It seems that his effectiveness is not what it seems, could you clarify that? The synthesis routes are interesting, especially Corey's and Hayashi's. There are many other aspects around Tamiflu that can provide a good context, such as shikimic acid, the lack of the drug during flu epidemics, and so on...
Thank you very much!!
Tamiflu is indeed quite the interesting story - I will put it on my list of potential videos!!
Meanwhile the drug to cure phobias is illegal and cheap
It's a treatment not a cure , the only cure to phobias that exist today that I know of is an amygdalotomy which is a bit extreme
What's that?
@@Huey_Freeman357 presumably MDMA
Given the wide array of phobias and their etiologies, it's just irresponsible to assert this. Some things work under some circumstances for some people.
Oh, and whichever one you had in mind should be legal, not on this flimsy and dishonest pretext, but because humans have bodily autonomy, and should not be forced to go to a potentially poisoned supply in order to exercise it.
@@Taygetea awesome
Thanks again for this well researched, informative and interesting video. It is always a pleasure, to get my brain massaged by life science und chenistry terms non-stop. I'd like to watch a video from you, investigating the revenues from other high selling small molecules (e.g. pregabalin), which are actually low in production cost. ❤
Thank you for your kind comment! I will keep some related videos coming.
so i know this isnt exactly what this episode is about, but it reminded me of my amazing cousin mikey he had hemophilia a and i just was going to ask if you would do a video that involves it in anyway whether its about it or something else... thanks man i appreciate you . rest in peace mikey i love u bubba
Thanks for your comment - may Mikey rest in peace
Trihexyphenidyl synthesis would be cool. I'm prescribed it and it's literally one of the CHEAPEST drugs I've ever been prescribed.
Yea of course its a good idea to name our pharmaceutical company something that sounds suspiciously close to eugenics.
🎉🔥🔥 I love your videos
Why is that alkylation enantioselective?
due to the chiral promoter in the form of quinine. Quinine is the well known organocatalyst. Better are their thiourea or squaramide derivatives, but this depends highly on reaction.
Quinine reacts first and is thus a chiral alkyl transfer reagent
@@totalsynthesis it reacts (creats new bond with quinine) or just simply catalyze this reaction due to oxonium-ion catalysis?
@@radeksuchy123 Yes (most likely). As shared in their original paper, there were some funky observations though so the ultimate mechanism was not determined.
"We first suspected that water was detrimental to the LDA reaction. Counter-intuitively, a consistently lower range of ee values was observed when moisture was vigorously excluded from the system. To follow up on this unexpected observation, we then spiked different amounts of water to the reaction mixture prior to the addition of a second equivalent of LDA. To our delight, water had a pronounced positive effect on the ee as shown in Table 2. The higher the water contents the better the ee with an optimum being 1.0 equiv. The same trend was also true for the yield. With added water, 95% ee was consistently achieved with either 6d or quinine. The added water was compensated by an equal equivalent of LDA. Interestingly, addition of solid LiOH, B(OH)3, MeOH, and AcOH had no effect on the ee. The mechanism is under further investigation."
(From J. Org. Chem. 2003, 68, 984)
@@totalsynthesis yeah, I read about it just minutes ego before you have posted your respond :D You have right about all of this, this funky situation with water also surprised me, very good topic for investigation, but there is one key factor - they are using 1.2 eq of quinine so there must be mechanism based on creating some bond between reagents. If the quinine acted like organocatalyst, they would use only catalytic amound of it (like 10% mol). So i have mistakenly assumed that it must be some sort of oxonium-ion catalysis. Or maybe quinine reacts in both ways, because the slightly deeper knowledge of organic chemistry lead to assumptions that our reality isnt black or white, it is in fact grey... ;)
4:00 wait what? sales cost more than twice as much as R&D? the marketing people must be geniuses or the researchers dumbasses lol
Yeah dude, most big pharma companies spend like $5-10bn in R&D - much more than that and they get pretty inefficient (large organizations, slow processes, no sense of prioritization). Employing people who sell the pharmaceuticals and managing the business is a bigger cost. The system sounds f'ed (and it kinda is) but medicines dont sell themselves - for bad and good reasons
I LOVE YOU I LOVE THIS CHANNEL
Thank you brother
Thank goodness that hepatitis c medications didn't end up in that high cost profile...
Especially looking at cumulative revenues those are some real heavy hitters as well
So there is a niche pharma market for only the most wealthy of people. Shocking huh, the rest of us a expendable while Billionaire can buy life.
Just wtite off the research and equipment and adminastration as charity 🎉