Remdesivir has a minor beneficial impact when delivered VERY EARLY.
No need to spread FUD when there's clinical data available.
There's still a couple of problems though:
* It has to be delivered by IV drip
* It's in short supply
* It's expensive
Which means that realistically, the only way to get a positive impact from it would be to send high-risk patients who were very likely to have just been exposed to the hospital for the injection. Even then, the risk-value proposition does not seem that great.
The bottleneck is that it's only slightly effective.
No hospital would take you in on slight symptoms. The drug alone costs $3,000+, it’s basically US-only and thus needs to be administered there, which will end up costing about as much again.
See the top 0.01% hold some remdesivir in their mansions for their private physician to administer.
I wasn't trying to spread FUD. I did state that the arrests weren't because of the drug.
So in theory it could save lives if it keeps Karen and Becky out of the ER.
https://www.gilead.com/purpose/advancing-global-health/covid...
Still if they can't keep up with demand and there are many lifes at stake, we should probably legislate a compensated invalidation of such a patent.
Sorry, my statement on legislation was ambigious. First, "we" was meant as "we the people of our respective countries," not limited to the US in any way. Secondly, it would probably create some international problems, so a combined effort would be nice. But I think companies should be compensated in such a case (hence "compensated invalidation") in a way that a company can reasonably accept.
> This process was not decided on as the most efficient by any sort of entity with an interest in public health - it's a private company performing a "goodwill" gesture.
I didn't claim that. I said it seems like an okay solution to that challenge (to me). This is independent from who came up with the idea.
As I felt it was phrased in a whay to supposedly make a reader angry, I questioned why that should be the case. Maybe that was over-interpreted by me. For the same reason I would accept this as an actual goodwill gesture. I have no trouble with the idea that richer countries have to pay more for making the development worthwhile and poorer countries benefiting from that at a cheaper price, as it seems like the humane thing to do to me.
I'm certain that the CEO knows just how fickle the patent is and wants to maintain as much control, gain as much money, favors etc while reducing risks, liability, losses etc.
The investment was made by the American people paying taxes. The profits will be privatized.
https://www.washingtonpost.com/business/2020/05/26/remdesivi...
Truly good/fair solution probably exists between nationalizing Gilead and Gileads opening bid.
[1] https://www.biopharmadive.com/news/new-drug-cost-research-de...
This section of your WaPo article hits the nail on the head:
>“Without incentivizing some of these companies to stay attached to emerging disease, I think they will walk away, even after this one,” he said. “In this situation [filing for a government patent] would have caused more harm with Gilead and not been worth it. “The government’s job is to make sure industry is successful, and if industry is successful, then we all benefit from it.” “Although USAMRIID performed extensive and critical screening and testing for Gilead, testing a compound and finding that it is indeed an effective antiviral compound does not qualify USAMRIID as a joint inventor of the compound,” Leigh Callander, chief patent counsel for the U.S. Army Medical Research and Development Command, said in an email.
https://www.nytimes.com/2001/10/24/business/a-nation-challen...
Other interesting results were:
Canada forced to honour Bayer's patent on ciprofloxacin (BMJ. 2001 Oct 27; 323(7319): 956. PMCID: PMC1172996)
> In an embarrassing mix-up, Canada's federal government will pay twice for a supply of the antibiotic ciprofloxacin (marketed as Cipro) that it ordered to protect Canadians in case they are faced with an outbreak of anthrax, as has happened in the United States.
...
> After a meeting of officials from the health department and both companies on Monday, the government announced it will still pay the generic firm the amount of its contract— $C1.3m (£580 000; $824 000)—and will buy another 900 000 tablets from Bayer. Bayer's price is said to be $C2.50 a tablet, compared with Apotex's $C1.50. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1172996/
Canadian government almost swamped by ciprofloxacin (BMJ. 2001 Nov 3; 323(7320): 1026. PMCID: PMC1173010)
> Canada's federal government has narrowly avoided having to pay for twice as much of the antibiotic ciprofloxacin (Cipro) as it thinks it needs to protect its citizens in the case of an outbreak of anthrax.
> The federal health department circumvented its own drug patent rules when it ordered about 900 000 tablets of the medication from a generic drug manufacturer, Apotex. The patent, held by Bayer AG, does not expire until 2004. Bayer reportedly threatened to sue. But after an announcement by the government that it would both pay the generic firm the amount of its contract—$C1.3m (£574 000; $825 000)—and buy another 900 000 tablets from Bayer, both drug companies let the health minister, Allan Rock, off the hook.
...
> Under the patent act, the government could have obtained authorisation to have a non-patented version of ciprofloxacin on a non-commercial basis, but it failed to ask for this.
Currently Gilead believe they can bring down their production time from 8-12 months 6-8 months, that means we won't see a large supply of this drug until 2021.
Why is something like this, with its silicon and sulphur atoms as part of the backbone, needed? Why wouldn't the same but with a more typical fully-carbon backbone work? If it's too complex a question, skip it, but thanks if you can shed light.
Certain “weird” metals like zinc, tin, and silicon (And these are the more normal ones) have been found to be able to help with this type of chemistry. The reason for why these metals are useful gets into orbital mechanics, but the core idea is that they can facilitate carbon-carbon bond formation.
The sulphur and fluorine are standard as part of the triflate functional group — it is a stable leaving group based on wanting electrons and being stable once it grabs those electrons (The sulphur can facilitate reasonable stabilisation).
> Why wouldn't the same but with a more typical fully-carbon backbone work?
Because a fully carbon backbone would not be as reactive and would not attach/detach from the intermediate as needed
https://www.statnews.com/2020/05/14/gilead-should-ditch-remd...
>The company has also developed GS-441524, another pro-drug that, as its name suggests, the body also converts into GS-441524 triphosphate, but in just in three steps. GS-441524 is easier to synthesize than remdesivir, requiring three steps instead of the seven needed for remdesivir.
>Researchers initially thought that remdesivir would be activated more quickly than GS-441524 in human cells infected with the SARS and MERS coronaviruses. Yet data from primary human airway epithelial cells — one of the most clinically relevant cell-based models of the human lung — showed no statistically significant difference in potency between the two compounds. When GS-441524 was used to treat cats with feline infectious peritonitis, a progressive and usually fatal disease caused by a coronavirus, it displayed remarkable safety and therapeutic efficacy, with 96% of cats recovering after treatment.
>Recent research in coronavirus-infected nonhuman primates demonstrated problems with remdesivir that inadvertently showed the antiviral effectiveness of GS-441524. In multiple studies testing remdesivir in coronavirus-infected mice or rhesus macaques, it was rapidly converted to GS-441524 in the bloodstream.
>Take the latest controlled study conducted in rhesus macaques infected with SARS-CoV-2: After remdesivir was administered intravenously, GS-441524 was present in serum samples at concentrations 1,000-fold greater than remdesivir. Upon completion of the study, the researchers found that only GS-441524 — not remdesivir — was detected in the macaques’ lungs, yet they exhibited no signs of respiratory disease, significantly reduced viral loads, and a distinct reduction in damage to lung tissue. Such results reinforce those obtained from a prior study, also in macaques, and data from other species that GS-441524 exhibits strong antiviral activity.
>The first step in the bioactivation of GS-441524 is the rate-limiting step, something that remdesivir was designed to avoid. But that doesn’t matter clinically because of remdesivir’s rapid transformation to GS-441524 in the bloodstream.
There is also a black market for GS-441524, which could be a reason Gilead doesnt want to promote it?
https://www.theatlantic.com/science/archive/2020/05/remdesiv...
https://www.uab.edu/news/health/item/11082-investigational-c...
Discovering (100s of)compounds in a lab (which is what the public funds pay for) is the easy and much cheaper part.
Testing it in humans and modifying it for that purpose is hard, expensive, and time consuming. Pretending like these drug companies do nothing and just take all the benefit from public research is incorrect.
If you want a lot of drug research, you probably want to ensure that successful drug research is lucrative. (Maybe less than today, maybe making unsuccessful research or negative reproduction more lucrative than today.)
In fact, I’m pretty sure the taxpayers are subsidizing investors with all the free research and knowledge they get from taxpayer funded higher educational facilities.
Developing medicines is a high risk venture. But the rewards are extremely high also, so maybe it merits the resources of all of society. This is ignoring that US taxpayers already pay for a significant portion of the R&D via universities.
There is nothing to stop that under the current model. It just isn't happening.
Reforming the FDA process could save an large amount of lives and money.
Some middle manager instructs a bunch of peons to look for places to cut costs. One of them finds that doing X costs Y when doing it another way could cost Z. This all gets packaged to a higher up who just sees it costs Y to do X, and writes a report noting that X is a result of W. This goes up the chain to someone who needs to evaluate whether to cut U,V or W and they recommend W because it ultimately costs Y. This goes up another level to someone who approves a budget that cuts W to save Y and packages this into some nice talking points. The CEO then presents these talking points to the board and is congratulated for saving Y and then move on to questioning why X isn't being done any more.
Every individual is making somewhat reasonable decisions from their myopic perspective but in aggregate they are incompetent. No one is deciding to let millions die, they simply don't take the time to understand what effects their actions have.
I plan to disagree, but first I need to know what the hell you're trying to say.
Now you have a decision to make: ignore your patent and your fiduciary duty to investors, or defend your patent in court and your right to profit from the drug you invented.
Yesterday you were a moral person, today you're faced with the chance to become one of history's greatest villains.
That's the crux of my earlier comment, with which you can now proceed to disagree.
(Note: in reality Remdesivir seems not to be an extreme life & death drug- it only shortens recovery time, so it wouldn't quite fit into the scenario I presented).
The great argument I wanted to make is that if there is a finite supply of a drug, only enough for 20% of the sick, selecting which 20% gets it doesn't cause more people to die. It might select who dies in deplorable or admirable ways, but the death count is the same.
But you're making a different and better argument.
I agree that your scenario would be terrible. But I don't think it describes what Gilead is doing. According to posts here, they're allowing generic manufacturing in poor countries, and India doesn't even respect drug patents to begin with.
This is what is done in patient outcome rankings for exotic therapies and surgeries that are a skill-based premium or are exceptionally expensive.
My perspective is, most small molecule therapeutics are already prioritized for production and trials based on synthesizability. So if some corporation really did find a viable treatment for COVID, I doubt scarcity would be the issue unless it fundamentally fails some medicinal chemistry principles for ease-of-synthesis. This is given how primed the global supply chain is to pump out a real treatment. Think of these checks as "code smell" checks, except in the early stages of drug development. Lead optimization is essentially the entire field of optimizing for desired properties, which is what would most likely be done to an extent if a molecule was prohibitively difficult to synthesize.
Btw, there's actually a LaunchHN on the frontpage that's right in the middle of tackling this kind of problem.
One would think this would be a rather large opportunity for them.
As a Canadian, I've seen our government repeatedly threaten to bypass US drug patents in the last trade war we had with the US.
And frankly, the cheaper drugs are for the consumer, generic or otherwise, the better. I'm certain that a life-saving drug won't be getting skipped because of a patent dispute.
Sorry, but if the one blessed company with the patent can't keep up with demand, and millions are going to die because there are patent restrictions, then ignore the patent laws and save some lives. It wouldn't look too good if the American government tried to stop it, essentially saying "It's against the law to save their lives, and we're going to punish you for saving them."