5 ms·

The article only mentions tests of GS-441524 on animals, but not humans, whereas remdesivir empirically seems to be reasonably safe in humans. Switching from th

The article only mentions tests of GS-441524 on animals, but not humans, whereas remdesivir empirically seems to be reasonably safe in humans. Switching from the one thing that actually possesses efficacy in humans to something that has mainly been tested on cats seems like an unnecessary gamble at this point.

icegreentea2 6y ago
Ideally we could work on both. Remdisivir is apparently nightmareish to produce - it's unlikely that that Gilead can fully capture all the value on the market with it alone, especially if another another therapeutic becomes available. That said, it makes plenty of sense why you would begin with your drug that has already passed clinical trials. I'm a bit disappointed that the article didn't emphasis this point. I'm certain the authors know about it, and even if they aren't out writing a hachet job, it can make this piece seem like one.
- refurb 6y ago
  In a world of limited resources, you have to make a call on which leads move forward in development. You can't move every program forward. And yes, remdesivir is a beast to make, but I don't think supply is an issue at all. They just packaged up and distributed 150 kg of it.
  - ggm 6y ago
    Are we in a world of limited resources in this specific sense? We're in a world of 3 trillion dollar re-ignite the economy. Whats the resource limitation here?
    - Slartie 6y ago
      Money does not magically create the personnel qualified in scaling up drug production, nor does it magically make the necessary, specialized machinery appear. Furthermore, as described in the article, the manufacturing appears to rely a lot on various businesses which each perform one specific step with a compound and hand over the result to the next, and Gilead's core work seems to be to find these businesses, provide missing know-how, and coordinate all of their work such that the timelines and amounts produced line up. Just dumping money into an economy also does not magically make such specialized businesses appear all of a sudden; self-organizing systems like modern capitalistic economies require time to adjust to big changes in demand or supply of certain goods or services.
      - ggm 6y ago
        I dislike Trump on principle and from the other side of the fence. I am a natural born 'big government' person. From my side of the fence, the one thing Trump said which made sense was: "there are 15 good candidate vaccines: we are pursuing all of them" That is exactly how the manhattan project ran: Thermal Diffusion, Gaseous Diffusion, Centrifuge and Calutron were all followed up, and it wound up that Thermal fed Calutron to increase yield but gaseous diffusion and centrifuges are what we use now. The point here is that they didn't penny-pinch "which one is better" they did them ALL
fspeech 6y ago
True but both are prodrugs and GS-441524 is downstream on the metabolic chain from Remdesivir.
- lend000 6y ago
  Interesting, do you have a source? So you're saying you get a dose of GS-441524 regardless as Remdesivir decays?
  - s1artibartfast 6y ago
    Yes, this was a central point addressed in the article
    - ggm 6y ago
      Its "upstream" in terms of being a 3 step drug not a 5 step drug and more of the active principle enters the bloodstream. So if we are in operations research linear programming mode, it may be less efficacious in some ways but its simpler to make and more of the active principle is liberated into the body. Would you rather have more drug to use on more people with more of it in the body, or a better drug but in shorter supply which needs a higher dose?
      - s1artibartfast 6y ago
        Yes, this was a central point addressed in the article
      - labawi 6y ago
        I understood the article as: most remdesivir is converted to GS, hence most of the effects should presumably be from GS. That would give a good chance of being actually upstream for most relevant purposes. > In multiple studies testing remdesivir in coronavirus-infected mice or rhesus macaques, it was rapidly converted to GS-441524 in the bloodstream.
        6y ago

icegreentea2 6y ago

Ideally we could work on both. Remdisivir is apparently nightmareish to produce - it's unlikely that that Gilead can fully capture all the value on the market with it alone, especially if another another therapeutic becomes available. That said, it makes plenty of sense why you would begin with your drug that has already passed clinical trials. I'm a bit disappointed that the article didn't emphasis this point. I'm certain the authors know about it, and even if they aren't out writing a hachet job, it can make this piece seem like one.

refurb 6y ago
In a world of limited resources, you have to make a call on which leads move forward in development. You can't move every program forward. And yes, remdesivir is a beast to make, but I don't think supply is an issue at all. They just packaged up and distributed 150 kg of it.
- ggm 6y ago
  Are we in a world of limited resources in this specific sense? We're in a world of 3 trillion dollar re-ignite the economy. Whats the resource limitation here?
  - Slartie 6y ago
    Money does not magically create the personnel qualified in scaling up drug production, nor does it magically make the necessary, specialized machinery appear. Furthermore, as described in the article, the manufacturing appears to rely a lot on various businesses which each perform one specific step with a compound and hand over the result to the next, and Gilead's core work seems to be to find these businesses, provide missing know-how, and coordinate all of their work such that the timelines and amounts produced line up. Just dumping money into an economy also does not magically make such specialized businesses appear all of a sudden; self-organizing systems like modern capitalistic economies require time to adjust to big changes in demand or supply of certain goods or services.
    - ggm 6y ago
      I dislike Trump on principle and from the other side of the fence. I am a natural born 'big government' person. From my side of the fence, the one thing Trump said which made sense was: "there are 15 good candidate vaccines: we are pursuing all of them" That is exactly how the manhattan project ran: Thermal Diffusion, Gaseous Diffusion, Centrifuge and Calutron were all followed up, and it wound up that Thermal fed Calutron to increase yield but gaseous diffusion and centrifuges are what we use now. The point here is that they didn't penny-pinch "which one is better" they did them ALL

fspeech 6y ago

True but both are prodrugs and GS-441524 is downstream on the metabolic chain from Remdesivir.

lend000 6y ago
Interesting, do you have a source? So you're saying you get a dose of GS-441524 regardless as Remdesivir decays?
- s1artibartfast 6y ago
  Yes, this was a central point addressed in the article
  - ggm 6y ago
    Its "upstream" in terms of being a 3 step drug not a 5 step drug and more of the active principle enters the bloodstream. So if we are in operations research linear programming mode, it may be less efficacious in some ways but its simpler to make and more of the active principle is liberated into the body. Would you rather have more drug to use on more people with more of it in the body, or a better drug but in shorter supply which needs a higher dose?
    - s1artibartfast 6y ago
      Yes, this was a central point addressed in the article
    - labawi 6y ago
      I understood the article as: most remdesivir is converted to GS, hence most of the effects should presumably be from GS. That would give a good chance of being actually upstream for most relevant purposes. > In multiple studies testing remdesivir in coronavirus-infected mice or rhesus macaques, it was rapidly converted to GS-441524 in the bloodstream.
      - 6y ago