16 ms·

> Pfizer’s phase 2/3 trial randomized non-hospitalized adult COVID-19 patients who were at high risk of progressing to severe illness to receive placebo or Paxl

> Pfizer’s phase 2/3 trial randomized non-hospitalized adult COVID-19 patients who were at high risk of progressing to severe illness to receive placebo or Paxlovid, a combination of the protease inhibitors PF-07321332 and ritonavir. The efficacy analysis is based on 1,219 patients. One noteworthy feature is the newness of this drug: > PF-07321332 was developed from scratch during the current pandemic. It’s a reversible covalent inhibitor that reacts with one of the main protease’s cysteine residues. Owen [director of medicinal chemistry at Pfizer] also discussed the chemistry involved in scaling up the compound. The first 7 mg of the compound were synthesized in late July 2020. Encouraged by the early biological data, the Pfizer team aimed to scale up the synthesis. By late October, they’d made 100 g of the compound. Just two weeks later, the chemists had scaled up the synthesis to more than 1 kg. Owen said 210 researchers had worked on the project. https://cen.acs.org/acs-news/acs-meeting-news/Pfizer-unveils-oral-SARS-CoV/99/i13 https://cen.acs.org/acs-news/acs-meeting-news/Pfizer-unveils... Less than two years from lab to clinic is highly unusual. If approved, I believe this would be the fastest lab-to-approval for a small molecule drug in the history of the FDA.

HWR_14 5y ago
>Less than two years from lab to clinic is highly unusual. I assume like most other COVID vaccines/treatments, the timeline is shrunk by going straight to more expensive phases of the trial instead of having preliminary ones of escalating cost and confidence. Or at least prepping for them. For instance, all the vaccines started setting up commercial production around the same time they started trials, because it's not worth the months delay of setting up a production line to determine if it worked first.
- acdha 5y ago
  Also one factor slowing some studies has been the need to wait for test cases: you can't infect people with, say, Ebola so you need to wait for enough people in your study cohort to contract it naturally to get enough data to say whether a vaccine candidate is having an impact. During a pandemic, it's sadly easy to hit a statistically-significant number of infections.
- sokoloff 5y ago
  This has interesting implications when we consider how much money drug companies “should” be paid for inventing important new life-saving medicines. I frequently hear/read complaints of "that's outrageous [that this medicine costs $X]!" Well, maybe it is; maybe it isn't, but if you make sure it costs $X/100, I can be pretty sure you'll get less drug R&D.
  - hellbannedguy 5y ago
    That's fine for new drugs. Not for generic drugs. And let us buy our meds out of country. (And buying out generic drug manufactures should other drug companies in order to decrease competition is not cool either.)
  - semi-extrinsic 5y ago
    Pharma companies in the US spend about twice as much on advertising as they do on R&D [1]. Recent data compiled by the House Oversight Committee shows the biggest pharma companies spent $56 billion more on stock buybacks and dividends than they did on R&D over the past five years [2]. Very little of the ridiculous prices that US citizens pay for medicine (directly or via insurance) actually goes towards R&D. [1] https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0050001 https://journals.plos.org/plosmedicine/article?id=10.1371/jo... [2] https://oversight.house.gov/sites/democrats.oversight.house.gov/files/COR%20Staff%20Report%20-%20Pharmaceutical%20Industry%20Buybacks%20Dividends%20Compared%20to%20Research.pdf https://oversight.house.gov/sites/democrats.oversight.house....
    - greeneggs 5y ago
      Your first link is from 2008, and analyzes data from 2004. I don't see how this proves anything, or even suggests much, about the industry today. Your second link shows that the pharma companies spend almost as much on R&D as on stock dividends and buybacks. Is there any other industry that spends as much on R&D? Apple, for instance, seems to be spending ~6x as much on stock buybacks and dividends as on R&D (approximately, based on the first Google hits). Even your own links contradict your claim that very little goes to R&D.
- azinman2 5y ago
  And that was due to the wisdom of operation warpspeed. Trump is under credited for this (whether his idea or not, he could claim it as such). What’s shocking to me is that he hasn’t been more pro-vax given we have the vaccines we do because of his administration.
  - Qub3d 5y ago
    Operation Warp Speed is, to me, an indication of the power of government "intertia". Trump changed a lot of things, and while an uncomfortable amount of the U.S. government seems to run on "tradition" that isn't actually law, after 4 years of unchecked assault it was only at the very end that it really got crazy. Warp speed is the work of career guys. Not even Fauchi -- he was important, but these ideas are put together, presented, and executed by the unknown 9-to-5ers.
    - Redoubts 5y ago
      > Operation Warp Speed is, to me, an indication of the power of government "intertia". We call this the Deep State
      - dragonwriter 5y ago
        > We call this the Deep State If by “we” you mean fans of the arbitrary, irresponsible, corrupt patronage-based governance of the spoils system who use the term to denigrate the idea of a professional civil service with loyalty that extends beyond the person of the current chief executive on whom their tenure depends, then, sure, “we” do.
      - azinman2 5y ago
        I find this whole deep state thing very strange. It's meant to sound ominous, but really it's just a bunch of career diplomates that have worked over many administrations who are the ones that make anything that works, work. We should be doing our best to preserve their knowledge and capability.
        5y ago
- Madmallard 5y ago
  The Latest article in BMJ about the failures in scientific integrity in the pfizer trials are a likely consequence of your last paragraph I would guess.
  - cblum 5y ago
    Can you provide a link to that?
    - Madmallard 5y ago
      https://www.bmj.com/content/375/bmj.n2635 https://www.bmj.com/content/375/bmj.n2635
UncleOxidant 5y ago
Development tools help accelerate software development. Better tools help you go faster. This is happening in biotech as well - they're getting some very good development tools.
ricardobayes 5y ago
Is anyone familiar how this scaling up process works? To what point can it be scaled up using lab methods, and at which point does it make sense to start making it large-scale?
- ivoras 5y ago
  There was an article specifically which explained that about remdesivir in really clear language but apparently it isn't there anymore. Here's a scholarly article on the evolution of synthesis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340098/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340098/
deanCommie 5y ago
> Less than two years from lab to clinic is highly unusual. If approved, I believe this would be the fastest lab-to-approval for a small molecule drug in the history of the FDA. It's sad that we all know people are going to use this fact to reject taking this medication while still chugging horse paste.
- a45a33s 5y ago
  "horse paste" has been approved for human use for over 30 years. not sure how expecting proper testing for new medicines became some conspiracy theory thing.
  - ceejayoz 5y ago
    As an antiparasitic. If you do a liver transplant for a congestive heart failure patient, you’ll lose your license, even if liver transplants are a neat and useful procedure.
    - a45a33s 5y ago
      ever heard of "off label use"?
snarf21 5y ago
Is the similiarity of COVID-19 to other coronaviruses also a speed up? We are not starting from complete scratch in that case.
- lrem 5y ago
  Aren't we? I thought that until SARS the scientific consensus was that coronaviruses are not interesting. And SARS died out too quickly to achieve much. But I might have not paid enough attention.
  - addicted 5y ago
    I’m pretty sure the reason Moderna was able to develop a vaccine so quickly (Feb 2020?) was because they already knew the spike protein to target from the original SARS outbreak.
osrec 5y ago
It's not uncommon for human tragedies to serve as a backdrop for significant scientific progress. Wars and pandemics seem to be the testbeds for medicine, where people are desperate enough to try anything, and legislation is relaxed accordingly. The biotech companies know this all too well, and take advantage when the opportunity arises.
catlikesshrimp 5y ago
This is something I haven't encountered before in biochemistry "reversible covalent" A chemical covalent bond. Maybe it means something else in this article?

HWR_14 5y ago

>Less than two years from lab to clinic is highly unusual. I assume like most other COVID vaccines/treatments, the timeline is shrunk by going straight to more expensive phases of the trial instead of having preliminary ones of escalating cost and confidence. Or at least prepping for them. For instance, all the vaccines started setting up commercial production around the same time they started trials, because it's not worth the months delay of setting up a production line to determine if it worked first.

acdha 5y ago
Also one factor slowing some studies has been the need to wait for test cases: you can't infect people with, say, Ebola so you need to wait for enough people in your study cohort to contract it naturally to get enough data to say whether a vaccine candidate is having an impact. During a pandemic, it's sadly easy to hit a statistically-significant number of infections.
sokoloff 5y ago
This has interesting implications when we consider how much money drug companies “should” be paid for inventing important new life-saving medicines. I frequently hear/read complaints of "that's outrageous [that this medicine costs $X]!" Well, maybe it is; maybe it isn't, but if you make sure it costs $X/100, I can be pretty sure you'll get less drug R&D.
- hellbannedguy 5y ago
  That's fine for new drugs. Not for generic drugs. And let us buy our meds out of country. (And buying out generic drug manufactures should other drug companies in order to decrease competition is not cool either.)
- semi-extrinsic 5y ago
  Pharma companies in the US spend about twice as much on advertising as they do on R&D [1]. Recent data compiled by the House Oversight Committee shows the biggest pharma companies spent $56 billion more on stock buybacks and dividends than they did on R&D over the past five years [2]. Very little of the ridiculous prices that US citizens pay for medicine (directly or via insurance) actually goes towards R&D. [1] https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0050001 https://journals.plos.org/plosmedicine/article?id=10.1371/jo... [2] https://oversight.house.gov/sites/democrats.oversight.house.gov/files/COR%20Staff%20Report%20-%20Pharmaceutical%20Industry%20Buybacks%20Dividends%20Compared%20to%20Research.pdf https://oversight.house.gov/sites/democrats.oversight.house....
  - greeneggs 5y ago
    Your first link is from 2008, and analyzes data from 2004. I don't see how this proves anything, or even suggests much, about the industry today. Your second link shows that the pharma companies spend almost as much on R&D as on stock dividends and buybacks. Is there any other industry that spends as much on R&D? Apple, for instance, seems to be spending ~6x as much on stock buybacks and dividends as on R&D (approximately, based on the first Google hits). Even your own links contradict your claim that very little goes to R&D.
azinman2 5y ago
And that was due to the wisdom of operation warpspeed. Trump is under credited for this (whether his idea or not, he could claim it as such). What’s shocking to me is that he hasn’t been more pro-vax given we have the vaccines we do because of his administration.
- Qub3d 5y ago
  Operation Warp Speed is, to me, an indication of the power of government "intertia". Trump changed a lot of things, and while an uncomfortable amount of the U.S. government seems to run on "tradition" that isn't actually law, after 4 years of unchecked assault it was only at the very end that it really got crazy. Warp speed is the work of career guys. Not even Fauchi -- he was important, but these ideas are put together, presented, and executed by the unknown 9-to-5ers.
  - Redoubts 5y ago
    > Operation Warp Speed is, to me, an indication of the power of government "intertia". We call this the Deep State
    - dragonwriter 5y ago
      > We call this the Deep State If by “we” you mean fans of the arbitrary, irresponsible, corrupt patronage-based governance of the spoils system who use the term to denigrate the idea of a professional civil service with loyalty that extends beyond the person of the current chief executive on whom their tenure depends, then, sure, “we” do.
    - azinman2 5y ago
      I find this whole deep state thing very strange. It's meant to sound ominous, but really it's just a bunch of career diplomates that have worked over many administrations who are the ones that make anything that works, work. We should be doing our best to preserve their knowledge and capability.
      - 5y ago
Madmallard 5y ago
The Latest article in BMJ about the failures in scientific integrity in the pfizer trials are a likely consequence of your last paragraph I would guess.
- cblum 5y ago
  Can you provide a link to that?
  - Madmallard 5y ago
    https://www.bmj.com/content/375/bmj.n2635 https://www.bmj.com/content/375/bmj.n2635

UncleOxidant 5y ago

Development tools help accelerate software development. Better tools help you go faster. This is happening in biotech as well - they're getting some very good development tools.

ricardobayes 5y ago

Is anyone familiar how this scaling up process works? To what point can it be scaled up using lab methods, and at which point does it make sense to start making it large-scale?

ivoras 5y ago
There was an article specifically which explained that about remdesivir in really clear language but apparently it isn't there anymore. Here's a scholarly article on the evolution of synthesis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340098/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340098/

deanCommie 5y ago

> Less than two years from lab to clinic is highly unusual. If approved, I believe this would be the fastest lab-to-approval for a small molecule drug in the history of the FDA. It's sad that we all know people are going to use this fact to reject taking this medication while still chugging horse paste.

a45a33s 5y ago
"horse paste" has been approved for human use for over 30 years. not sure how expecting proper testing for new medicines became some conspiracy theory thing.
- ceejayoz 5y ago
  As an antiparasitic. If you do a liver transplant for a congestive heart failure patient, you’ll lose your license, even if liver transplants are a neat and useful procedure.
  - a45a33s 5y ago
    ever heard of "off label use"?

snarf21 5y ago

Is the similiarity of COVID-19 to other coronaviruses also a speed up? We are not starting from complete scratch in that case.

lrem 5y ago
Aren't we? I thought that until SARS the scientific consensus was that coronaviruses are not interesting. And SARS died out too quickly to achieve much. But I might have not paid enough attention.
- addicted 5y ago
  I’m pretty sure the reason Moderna was able to develop a vaccine so quickly (Feb 2020?) was because they already knew the spike protein to target from the original SARS outbreak.

osrec 5y ago

It's not uncommon for human tragedies to serve as a backdrop for significant scientific progress. Wars and pandemics seem to be the testbeds for medicine, where people are desperate enough to try anything, and legislation is relaxed accordingly. The biotech companies know this all too well, and take advantage when the opportunity arises.

catlikesshrimp 5y ago

This is something I haven't encountered before in biochemistry "reversible covalent" A chemical covalent bond. Maybe it means something else in this article?