
Expanded access programs for Remdesivir - mudil
https://www.gilead.com/stories/articles/an-update-on-covid-19-from-our-chairman-and-ceo
======
cm2187
Stupid question in case anyone here has a medical background.

I was under the impression that covid19 was a two step process. First the
virus infects and attacks the protective layer of the lungs (causing cough and
fever). Then, the damage done to the protective layer of the lungs results in
an infection / pneumonia, and that's where people have respiratory problems
and may be in critical condition. But at this stage the viral load is low and
the virus isn't the problem anymore, the pneumonia is [1].

This is why I thought Pr Raoult was advocating for the use of chloroquine in
the early days of the disease, combined with prompt testing.

But it seems that anti-virals (like the study mentioned in this post and other
studies in the US and Europe) are tested on patients in critical phase, i.e.
with serious cases of pneumonia. Am I missing something or should we not
expect anti-virals to be of much use in those cases, as it is too late, we are
not dealing with a virus but with a pneumonia?

[1] see this useful video: [https://www.youtube.com/watch?v=BtN-
goy9VOY](https://www.youtube.com/watch?v=BtN-goy9VOY)

~~~
lbeltrame
There's a trial[1] whose objective is to determine if chloroquine is actually
useful early on in the infection.

With a target sample size of 3000 individuals it would have at least
sufficient numbers to show if it's actually viable, helps a little, or does
not help at all.

[1]
[https://clinicaltrials.gov/ct2/show/NCT04308668?term=hydroxy...](https://clinicaltrials.gov/ct2/show/NCT04308668?term=hydroxychloroquine&recrs=ab&cond=COVID-19&draw=2)

~~~
brutt
Also,in France: [https://www.mediterranee-
infection.com/covid-19/](https://www.mediterranee-infection.com/covid-19/)

~~~
tonfa
Tho they've focused mostly on care instead of the science (they don't believe
in randomized trials), and it's going to be hard to know if the treatment is
efficient from those (the EU and Michigan studies should help figuring that
out).

~~~
vanniv
In the absence of other viable treatments, the efficiency isn't really
important.

Frankly, if it is only modestly effective, it should still be given to
everyone without contraindications.

Efficiency only becomes important in a year or two when there are competing
therapies.

When the choices are Chloroquine or Hopes and Prayers, Chloroquine is the
obvious choice (for those that don't have the contraindications, of course --
for those patients, you'd need more evidence to know that the benefits
outweighed the risks)

------
aluminussoma
Remdesivir was one of the earliest promising candidates to treat covid-19
since it had promising results - in the lab - against other coronaviruses like
SARS and MERS. It did not have results in humans because those viruses went
away before in vivo testing could be performed.

Will it work? If it was a runaway success, I would have expected any of the
current clinical trials to be cut short as the difference between placebo and
non-placebo patients would have been obvious. That hadn't happened. I'm still
hoping it has some positive effect.

The drug also had to administered through an IV over several days. It is not a
pill you take. If it works, this makes treatment a little bit more difficult.
You can't just give patients a pill and send them home.

------
Tepix
_Gilead is providing the entirety of this existing supply at no cost, to treat
patients with the most severe symptoms of COVID-19. The 1.5 million individual
doses are available for compassionate use, expanded access and clinical trials
and will be donated for broader distribution following any potential future
regulatory authorizations. These doses are for treating patients with severe
symptoms, through daily intravenous infusions in a hospital setting. Having a
potential treatment in our hands comes with significant responsibility.
Providing our existing supplies at no charge is the right thing to do, to
facilitate access to patients as quickly as possible and in recognition of the
public emergency posed by this pandemic._

I'm glad to hear this!

------
daenz
>The safety and efficacy are not yet known so while we feel the greatest sense
of urgency in our work with remdesivir, we must take the responsible, ethical
approach of determining whether it is indeed a safe, effective treatment.

>we continue to provide remdesivir on an individual compassionate use basis
for children and pregnant women.

Can someone explain this logic to me? The safety and efficacy is not known, so
we're going to give it to the most vulnerable people first?

~~~
ISL
If someone is going to die anyway, a research drug that might save them sounds
pretty awesome.

~~~
Waterluvian
But children are of least concern. Or do they mean children who are going to
die? How many instances of that are there?

And pregnant women? That's hard to reconcile with common sense.

~~~
dpbriggs
Are you unaware that judgement will be used?

Compassionate uses are hail marys and are used appropriately.

------
underdeserver
As with anything pharmaceutical - they still need to make sure it doesn't have
long term side effects. As horrible as it is to prevent treatment and prolong
suffering, it would be more horrible if thousands of people suffer from
unknown side effects if they would have recovered without it.

~~~
cm2187
So you advocate to not use any new molecule until we have studied the effects
over 5-10 years?

~~~
QUFB
False dichotomy much? This is a nuanced issue, and the parent comment didn't
suggest this at all.

~~~
cm2187
Well, how do you know the long term effects if you don't study the effects
over a long period?

------
baxtr
_> Remdesivir is still an investigational medicine and has not been approved
by regulatory authorities anywhere in the world. The safety and efficacy are
not yet known so while we feel the greatest sense of urgency in our work with
remdesivir, we must take the responsible, ethical approach of determining
whether it is indeed a safe, effective treatment. This is why multiple
clinical trials for remdesivir are underway, involving thousands of patients
with COVID-19 across the world._

------
RivieraKid
It's surprising and disappointing that production takes 6 months, that's well
beyond the peak of the pandemic.

~~~
benchtobedside
See this recent article on HN that addresses how difficult it is to
synthesize: [https://www.acsh.org/news/2020/03/26/problem-remdesivir-
maki...](https://www.acsh.org/news/2020/03/26/problem-remdesivir-making-
it-14665)

------
sadfev
Didn’t the Japanese rule this drug out saying it’s totally ineffective?

------
DominikPeters
I’m not too glad. From the description, it sounds like it’s a massive expense
to produce the drug, and if public attitudes force companies to give the
results away for free, then there is no expectation of profits for pharma
companies to invest for future preparedness for pandemics. I’d like them to
charge a lot and make a killing. Governments can subsidize if they want.

~~~
basilgohar
You should be glad. Pharma companies are well-known historically to have
milked monopolies to their own financial favor at the cost of public health,
well-being, and welfare. They are not traditionally seen nor acting in
congruence with altruism. If a company has decided to do so, that is great.
But I think seeing this as some sort of a slippery slope seems completely
backwards to me. It's about time pharma companies cut a little of their
profits for the benefit of people. The cost of research is far outweighed by
their excessive profits that come after the fact.

~~~
avalys
I don't know how you can complain about "excessive profits" for entirely novel
products that a drug company brings into existence, essentially, starting from
nothingness. No amount of profit is excessive - the profit is the motivation
for them to invest in further research and we should all hope it continues to
be so. "Profit" directly represents how much value to society their drug
produced. If someone cures cancer, are you going to whine about how much money
they make from it? Are you going to claim that, because they produced
something extremely valuable, society has the right to take it from them for
less than it's worth?

This is not the same as, say, an ISP making excessive profits by manipulating
the market and building themselves a quasi-monopoly, or a bank harvesting
profits by taking huge risks with the understanding that the Federal Reserve
will bail them out if everything blows up. The ISP isn't innovating, isn't
creating anything, they're merely an engine for spending and allocating
resources. The bank isn't creating anything either, they're just moving money
around and playing social engineering games with society. Complaints about
profits in these industries are totally reasonable, since these companies are
basically just middlemen sucking money from the economy in order to maintain
the plumbing.

But to complain about excessive profits in an industry whose entire purpose is
to discover new things? That makes no sense to me. What alternative would you
prefer?

~~~
ejstronge
> The bank isn't creating anything either, they're just moving money around
> and playing social engineering games with society

How would you react to a situation in which small companies discovered new
drugs for ~$10 million, building on public research, and then were purchased
by larger pharma companies for ~$300 million, and in which the large pharma
companies aimed to earn ~$1-5 billion before the patents on the small
company's invention expire?

~~~
s1artibartfast
I would say that there is a common misunderstanding of:

A) the viability initial drug discovery and subsequent development costs, and

B) The time value of money.

For A) success rates of 5000:1 are not uncommon. Discovery is at the very
beginning of this process [1],which can take 12–15 years and cost in excess of
$1 billion [2]

B) A 1 to 5 billion dollar return on a 300 million acquisition is likely a
loosing proposition for most pharma companies due to risk and the time value
of money. If you have a 300m acquisition, 700m additional dev costs, a 50%
time discount, and a 50% chance of success, you are already up to 4 billion in
revenue needed to break even. This article [3] provides a balanced overview of
the finical aspect and is written by a scientist trying to give away a cure
for his terminal wife.

[1]
[https://en.wikipedia.org/wiki/Hit_to_lead](https://en.wikipedia.org/wiki/Hit_to_lead)
[2]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058157/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058157/)
[3] [http://www.cureffi.org/2019/04/29/financial-modeling-in-
rare...](http://www.cureffi.org/2019/04/29/financial-modeling-in-rare-
disease/)

~~~
ejstronge
I agree with your comment in general, but I would just underline that the
discovery component of a drug is often not paid for by the eventual vendor of
the drug, but is instead paid for by taxpayers, other granting agencies, and
venture capitalists. Thus the eventual vendor of a drug won't necessarily have
5000:1 odds, but instead will be able to review and purchase the most
promising candidate drugs based on data generated by other companies.

It's definitely true that companies also attempt to make new drugs in-house,
but I can't readily recall a recent blockbuster drug made in this way.

The expensive part of bringing new drugs to market is testing in humans.
Perhaps the US could bear some of these costs while, in exchange, shortening
or eliminating patent protections.

~~~
s1artibartfast
>I agree with your comment in general, but I would just underline that the
discovery component of a drug is often not paid for by the eventual vendor of
the drug, but is instead paid for by taxpayers, other granting agencies, and
venture capitalists.

In the case of the taxpayers and grants, i think it is important to keep in
mind that these are explicitly given without strings attached or rights
reserved because society decided that we want to encourage private research.
It is fair to argue that perhaps we should change the model moving forward,
but I find it fairly offensive when folk claim a retroactive ownership on this
basis.

>Thus the eventual vendor of a drug won't necessarily have 5000:1 odds, but
instead will be able to review and purchase the most promising candidate drugs
based on data generated by other companies.

I wholeheartedly agree. the long >5000:1 is at discovery, i.e. the basic
research that is often publicly funded. Once drugs have gone through enough
screening to be used, the probability of approval is up to about 10:1 [1]. A
lot of the bigger sales take place between phase 1 and 2, which probability of
approval is up to perhaps 25%. Research institutions and early developers get
paid based on the potential value and risk, and are not taken advantage of.
The fact that companies often outsource early develop doesn't invalidate the
their claim to their profits.

>The expensive part of bringing new drugs to market is testing in humans.
Perhaps the US could bear some of these costs while, in exchange, shortening
or eliminating patent protections.

This is an interesting idea. Two additional options that you may want to
consider that wouldn't stifle development are expedited approval and
government manufacture of generics. Due to the time value of money, faster
approval increases the profitability of new drug development and without
increasing prices to consumers. For generics, drug profits after loss of
exclusivity are so far out that they don't significantly weigh in on the
decision to develop a product or not.

------
ltbarcly3
There are a ton of studies ongoing, stock pumping PR campaigns like this
aren't responsible until the data is in, and there should be studies breaking
their blinds this week. It's fine to ramp up production just in case, but that
hardly justifies a press release by the CEO.

