
How remdesivir works, and why it's not the ultimate coronavirus killer - chmaynard
https://scopeblog.stanford.edu/2020/06/29/how-remdesivir-works-and-why-its-not-the-ultimate-coronavirus-killer/
======
kens
There's a nice diagram from _Science_ that shows how Remdesivir and other
potential anti-coronavirus drugs work:
[https://science.sciencemag.org/content/sci/368/6493/829/F1.l...](https://science.sciencemag.org/content/sci/368/6493/829/F1.large.jpg)

~~~
acqq
The picture is from
[https://science.sciencemag.org/content/368/6493/829](https://science.sciencemag.org/content/368/6493/829)
published "22 May 2020" at the time when less was known about Chloroquine and
hydroxychloroquine than today about treating Covid-19 (1). That's the needed
perspective when watching the picture, where the rest is still relevant.

\-----

1)

E.g. June 23, 2020 "NIH: Trial Investigating Hydroxychloroquine for COVID-19
Stopped"

[https://www.empr.com/home/news/hydroxychloroquine-trial-
halt...](https://www.empr.com/home/news/hydroxychloroquine-trial-halted-
unlikely-to-benefit-covid19-patients/)

17 June 2020 "“Solidarity” clinical trial"

[https://www.who.int/emergencies/diseases/novel-
coronavirus-2...](https://www.who.int/emergencies/diseases/novel-
coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-
clinical-trial-for-covid-19-treatments)

"hydroxychloroquine does not result in the reduction of mortality of
hospitalised COVID-19 patients, when compared with standard of care."

And before, Jun. 9, 2020: "Three big studies dim hopes that hydroxychloroquine
can treat or prevent COVID-19":

[https://www.sciencemag.org/news/2020/06/three-big-studies-
di...](https://www.sciencemag.org/news/2020/06/three-big-studies-dim-hopes-
hydroxychloroquine-can-treat-or-prevent-covid-19)

~~~
jakeogh
[https://aapsonline.org/preliminary-injunction-sought-to-
rele...](https://aapsonline.org/preliminary-injunction-sought-to-release-
hydroxychloroquine-to-the-public/)

more:
[https://news.ycombinator.com/item?id=23405435](https://news.ycombinator.com/item?id=23405435)

and: [https://defyccc.com/another-junk-anti-hydroxychloroquine-
stu...](https://defyccc.com/another-junk-anti-hydroxychloroquine-study-2/)

~~~
acqq
From that link:

"AAPS files with the court a chart showing how countries that encourage HCQ
use, such as South Korea, India, Turkey, Russia, and Israel, have been far
more successful in combatting COVID-19 than countries that have banned or
discouraged early HCQ use, as the FDA has."

However: that chart is totally misleading, it's a typical "non sequitur".
"Case fatality rate" is just a ratio "death" through "cases". Where those with
weaker symptoms are recognized as "cases" the rate is lower. How they are
recognized is not the same across different countries.

~~~
jakeogh
Agreed. Excess mortality is the real measure.

Note, you seem to be posting studies that did not pair HCQ with zinc, _and_
are not using it prophylactically. Is my understanding correct?

For example: [https://www.sciencemag.org/news/2020/06/three-big-studies-
di...](https://www.sciencemag.org/news/2020/06/three-big-studies-dim-hopes-
hydroxychloroquine-can-treat-or-prevent-covid-19) links to
[https://www.recoverytrial.net/files/hcq-recovery-
statement-0...](https://www.recoverytrial.net/files/hcq-recovery-
statement-050620-final-002.pdf) which does not mention zinc, and it's patients
admitted to the hospital (not prophylactic). Digging further, to the source
given in that pdf, not a mention of zinc:
[https://www.recoverytrial.net/@@search?SearchableText=zinc](https://www.recoverytrial.net/@@search?SearchableText=zinc)
which is the whole point of using HCQ in the first place.

~~~
acqq
> you seem to be posting studies that did not pair HCQ with zinc

I'm just posting studies that were the basis for what FDA decided June 15,
2020 (1):

"FDA has _revoked the emergency use authorization (EUA)_ to use
hydroxychloroquine and chloroquine to treat COVID-19 in certain hospitalized
patients when a clinical trial is unavailable or participation is not
feasible. We made this determination based on recent results from a large,
randomized clinical trial in hospitalized patients that found these medicines
showed no benefit for decreasing the likelihood of death or speeding
recovery."

And I don't have more information than that.

1) [https://www.fda.gov/drugs/drug-safety-and-
availability/fda-c...](https://www.fda.gov/drugs/drug-safety-and-
availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-
covid-19-outside-hospital-setting-or)

------
remote_phone
The biggest problem with remdesivir is that it is administered intravenously.
That makes it very hard to administer unless the patient is in the hospital.
What would be ideal is if they had it in pill form, and then anyone with early
symptoms could get pills instead. But without that option right now it makes
it too late to administer unless the patient is already in severe condition.

They are planning on testing an inhalant version but who knows where that will
land in terms of effectiveness. It might make things worse so that is much
further out unless things are really lucky, which we haven’t had a lot of with
coronavirus.

~~~
wbl
Every heroin junkie gives themselves IV injections. It's not hard.

~~~
raverbashing
You're right but an injection is not an infusion.

An infusion is something that takes a longer time as the drug is taken slowly
into the bloodstream (might be something that takes a couple of hours).

------
SomeoneFromCA
I am wondering, Wikipedia claims that the active metabolite of this drug is a
medicine for cats sold on black market; what is the price? I am sure it is way
less than the ridiculous price they want for Remdesivir.

~~~
roywiggins
Apparently as much as $12,000 for a 12-week course.

[https://www.theatlantic.com/science/archive/2020/05/remdesiv...](https://www.theatlantic.com/science/archive/2020/05/remdesivir-
cats/611341/)

Gilead is charging less than that for Remdesivir.

[https://www.cbsnews.com/news/gilead-coronavirus-treatment-
re...](https://www.cbsnews.com/news/gilead-coronavirus-treatment-remdesivir-
private-insurance-cost/)

~~~
SomeoneFromCA
I was wrong then. So cat owners should start buying remdesivir then.

~~~
ethbro
> So cat owners should start buying remdesivir then

Yes! For many reasons.

[https://www.cdc.gov/media/releases/2020/s0422-covid-19-cats-...](https://www.cdc.gov/media/releases/2020/s0422-covid-19-cats-
NYC.html)

------
pazimzadeh
Nucleoside analogs are notorious for breeding resistance, which is why they
should ideally be used in combo with other drugs.

------
claudeganon
IIRC, Gilead has tried to pull this drug off the shelf as a cure multiple
times, for different diseases, only to have it proven to not be very
efficacious.

As soon as they announced it as a COVID treatment, I assumed it was another
cash grab while people are confused, desperate, and scared.

~~~
s1artibartfast
That seems like a pretty cynical take. My understanding is that Gilead has
been donating the drug and provided a royalty free license to other pharma
companies to manufacture it (not that they could).

~~~
claudeganon
They just announced something like a 7K per treatment price schedule for the
drug, and it was largely developed at tax payer expense through a DoD scheme,
so I’ll stick to my skepticism. The WHO also accidentally released some study
data showing that drug showed no improvement in COVID outcomes:

[https://www.statnews.com/2020/04/23/data-on-gileads-
remdesiv...](https://www.statnews.com/2020/04/23/data-on-gileads-remdesivir-
released-by-accident-show-no-benefit-for-coronavirus-patients/)

~~~
s1artibartfast
I agree that any price is too high if it simply doesn't work. I don't find the
public funding critique particularly compelling because it is exactly what the
public signed up for. The we fund private medical research and development
because we want the more products brought to market by those firms. The reward
is that the product exists at all.

I do think that there is a compelling argument for the the government trying
to do more drug development and then licensing or open-sourcing the product.

~~~
Archio
>The reward is that the product exists at all.

Why do VCs get any return from startups? Isn't the reward that the startup
exists at all?

Better yet, why does Gilead get to write a press release explaining the reason
they're asking $3k per person for the drug is so they can "invest in
scientific innovation that might help generations to come"? Isn't the reward
the money they initially got from the government?

I am getting pretty sick and tired of public money getting used – and rightly
so – to fund innovate medical research, and then any and all benefits or
profits from the results of that resesarch being privatized.

~~~
s1artibartfast
VCs get returns because they negotiate them upfront. I have never heard of a
VC that donates money and then tries to go back and negotiate terms with the
companies that IPO.

If you are tired of giving away public money, negotiate terms.

~~~
claudeganon
You’re talking about investment schemes operating several layers deep inside
government bureaucracies. We should absolutely have legislation that mandates
that public investment in drugs is returned to the public in kind, but it’s
hand-waiving to pretend that the people on the receiving end of high drug
prices should’ve negotiated better prices for themselves, or that drug
companies wouldn’t throw everything they have to stop such measures being put
in place.

~~~
s1artibartfast
>We should absolutely have legislation that mandates that public investment in
drugs is returned to the public in kind

I don't think this more of a policy problem than a legislation policy. The US
government can simply stop giving away free money at any point it wants.

>it’s hand-waiving to pretend that the people on the receiving end of high
drug prices should’ve negotiated better prices for themselves

I think you may have missed the point I was making in my last post. I am not
saying that drug consumers should negotiate better prices (although this is
how prices are controlled in every other first world country). What I was
saying that the US government intentionally gives away money with no strings
attached for R&D. The explicit purpose of this funding is to help companies
make products and profit. If the outcome you want is different, we need to
look at different terms or a different investment vehicles.

One simple option would be requiring recipients of federal research grants to
publish in open journals and open source their patents. the down side, is that
this may reduce the chances of them being developed at all.

In addition to the US government, there are similar challenges for non-profits
and charities, which often give money to large drug developers, or sell
internally developed drugs to the for profit sector. You might find this paper
interesting [1] as well as the history of ivacaftor.

[1]
[https://www.tandfonline.com/doi/full/10.1080/20016689.2018.1...](https://www.tandfonline.com/doi/full/10.1080/20016689.2018.1545514)

