The Disturbing Truth About New Medicines: Are They Really Better? (Pharmaceutical Chemistry)
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- Опубліковано 1 чер 2024
- 🤑 Are newly approved drugs indeed therapeutically superior to already existing medicines? Does their pricing reflect their benefit? Are drugs with breakthrough designations and accelerated approvals actually more impactful than normal therapeutics? Watch this video to learn about these elements and more!
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00:00 Expensive, useless drugs, bankruptcy and chemistry
00:49 Rising healthcare and drug costs
01:58 "Me-too drugs" vs. therapeutically high-value drugs
02:41 Study #1: Are new drugs better? First versus supplementary indications
05:48 Study #2: Are accelerated drugs more valuable? Breakthroughs, fast track, priority review and accelerated approvals
07:43 Study #3: Are low benefit drugs cheaper than high benefit medicines?
08:44 "Useless" drug #1: Avastin in metastatic breast cancer (overall survival, progression free survival)
12:02 "Useless" drug #2: Rucaparib in ovarian cancer
13:37 Chemistry A: Large-scale process route (nitration, Leimgruber-Batcho)
15:04 Chemistry B: Streamlined organic synthesis (Heck, imino-Stetter Umpolung)
16:52 THANK YOU for your support!
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 UA-cam.
Key sources:
- Study #1: Therapeutic value of first versus supplemental indications of drugs in US and Europe (2011-20): retrospective cohort study: BMJ 2023, 382, e074166
- Study #2: Association between FDA and EMA expedited approval programs and therapeutic value of new medicines: retrospective cohort study: BMJ 2020, 371, m3434
- Study #3: Prices and clinical benefit of cancer drugs in the USA and Europe: a cost-benefit analysis: Lancet Oncology 2020, 21, 664
- The US FDAs withdrawal of the breast cancer indication for Avastin (bevacizumab): Saudi Pharm J 2012, 20, 381
- Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: Results from AVADO: Eur J Cancer 2011, 47, 2387
- Paclitaxel plus Bevacizumab versus Paclitaxel Alone for Metastatic Breast Cancer: N Engl J Med 2007, 357, 2666
- Multikilogram Scale-Up of a Reductive Alkylation Route to a Novel PARP Inhibitor: OPRD 2012, 16, 1897
- Total Synthesis of Rucaparib: JOC 2022, 87, 4813
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) - Наука та технологія
Let me know your thoughts and questions on the video. Are the pharmaceutical-focused ones interesting at all? I'm working on more organic chemistry-focused, as well as psychedelic science videos - so hopefully we keep a good mix going forward.
💘 Massive thank you to all channel supporters!
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I'm concerned about the jak inhibitors - immunomodulatory drugs that are very new, being used for moderate skin conditions? And they come up with a new one every year.
Thank you for informing people about the financial factors that go into making and pricing pharmaceutical drugs. It's a very important issue that society needs to actively engage with. So many people have an intuition about what "feels fair" when it comes to drug prices but it's not based on anything grounded in reality, unfortunately. And the pharma companies do themselves no favours by obscuring their processes and only answering to share holders. The more we know about the costs and risks that span the entire drug R & D lifecycle the better because then we can start to form a realistic picture of the massive task that it is, and contrast this with what governments are capable of. In some ways it makes sense that private industry are the only ones capable of developing drugs because the research effort and risk is huge, gov simply don't have it in their budget. I could go on and on but I'll leave it to more capable and engaging individuals such as yourself :) I appreciate everything you're doing here on this chan and would love to see more videos like this one.
@@vr7861 hey man, thanks so much for the comment! It's nice to see some people are interested in these topics as well - I'm actually surprised this video has attracted so few viewers, maybe the algo played some tricks on me given the topic...
To me, the hepatitis c cures are impressive. The old method of treatment for that disease was chemo lite, at least based off the side effects, and mostly didn't lead to a cure, just a remission
I saw a lecture by Nobel Laureate (she was awarded for click chem), she was presenting some stuff that sialic acid on surface glycoproteins is the other pathway for tumor immune suppression. So they are working on attaching sialidazes to some antibodies to strip off sialic acid from tumors. Maybe this will be a nee big thing (although there is a big question of targeting those sialidases to the right place, right now they are testing it with herceptin)
Yeah, the old treatmemt was interferon.. which is a drug with torturous side-effects and treatment-wise was a total gamble, with a very low cure rate (like 20-30% at best I think, those may be generous numbers still).
The new Hep C drugs are one dose a day of one or two pills for about 5 weeks, with almost no side effects and a 95%+ cure rate. Basically the new Hep C cure is a miracle drug, what more could you ask for? One pill a day, almost no side effects (any suffered are usually mild), and an almost guaranteed cure.
And although after being cured you will have Hep C antibodies in your blood forever, it actually doesnt make you immune so you can be re-infected.
Literally the only problem arose from pharma greed when they first made it, it became the most expensive drug in the world, no exagerration, at $80,000-$100,000 USD for your one bottle of pills (~35 cheaply manufactured pills). Pretty disgusting. Thankfully my gov. negotiated the price and offered it 100% covered if you were signed up for a certain program.
For a while getting cured had nothing to do with treatment but trying to find a way to have this exorbitant price tag covered, it was a real mess for a few years. Idk wtf uninsured americans did to get treated.
Either way I forever salute the thousands of doctors and nurses who did the research to make this incredible breakthrough possible❤❤
(There's an incresibls TED talk about the journey to curing Hep C including the pharma greed.
Very based content sir
Thank you!
Me too drugs are not always a bad thing. Despite having the same mechanism of action, "me toos" can offer unexpected or even unexplained benefits. Examples include statins and SSRIs. They also offer the benefit to patients in terms of drug cost - with more options on the market, companies are not able to command such high prices compared to monopoly markets.
Edit - also the benzodiazepines - incredibly similar drugs structurally but they span a range of half lives which gives wider utility for a wider range conditions i.e. acute anxiety vs severe epilepsy / seizures. Z-drugs then followed which also act on a very similar pathways but with different binding to the GABA receptor, resulting in decreased abuse potential.
Agree
There are minor genetic differences in population that makes people respond a bit differently to each drug compound. I think it’s good to have pharmacokinetic options out there just in case 😊
awesome video and a great mix of content. keep it up man
Thank you!
Thank you for this.
I have treatment resistant Crohn's and it seems every 5 years a new drug comes out that does nothing for me. I always wondered why and this video gives me an idea.
I've just finished a module on drug discovery and this video beat the shit out of the way it was presented in my course. Nice work! 👍
😂😂 thank you!
@@totalsynthesis Nope, thank _you!_
That's literally what's expected outcome. It's surprising that actual breakthroughs are actually this common.
I think e.g. 13% of all non-accelerated drugs (from the second analysis) so 1 out of 8 being better than existing therapies is low! But you are correct that we should not expect the majority to be high value
@@totalsynthesis Majority? I wasn't expecting even 12%.
It's basically gambling for a breakthrough.
@@lloydgush Probably we just have different expectations - but I would expect if a drug successfully gets carried through the entire development process - with already ~10% cumulative success chance in the clinic only - it would be more than 13% ultimately. Simply also because development costs are high and the commercial return of a e.g., undifferentiated third-to-market drug is quite low as well. In any case, we should get better at this in future but as we reach the limit of what we can treat with our science, this will get more and more challenging.
New cancer drugs are meh but there are interesting new drugs that are great , orexin based drugs for sleep and narcolepsy are a great example
Definitely - there are many exciting areas (in basically every disease) but also some areas with lower degree of innovation!
Buuuut, look how we already have 3 or 4 different ones, like allvtheir all copycats. Like how prozac led to Zoloft, luvox, paxil, Lexapro and celexa, I'm sure I'm missing some, all SSRI drugs with only 2 having unique modes of action (prozac, serotonin 2c agonist and luvox being a sigma agonist)
@@90klhif we ignore the MOA there are still some positives , some people seem to get really bad side effects of one ssri but non with another ssri because of how some people metabolize some drugs . But I do agree with you
Thats a good point