
With no prospects for profits, big pharma neglects new infectious diseases - mmoya
https://www.swissinfo.ch/eng/covid-19_with-no-prospects-for-profits--big-pharma-turns-back-on-new-infectious-diseases/45598436
======
refurb
What's needed is a new payment model for anti-infectives. This already happens
at a small scale with grants from institutions like BARDA. The DOD of also
does this for vaccines for biological weapons like anthrax where there is a
high likelihood the drug will never be used, but a vaccine is needed because
if there is an outbreak, the consequences are severe.

Basically, rather than paying for drugs on a per unit basis, you pay a lump
sum for access to the drug. This solves the issues of spending $100M to
develop a new treatment for some disease where there is never a outbreak and
you cover none of the cost of R&D.

There have been ideas to have X-Prizes for new antibiotics. Discover a new
drug for a anti-biotic resistant infection? Great, here is $500M as long as
you agree to produce as much drug as needed for free or some nominal cost.

~~~
_bxg1
> Basically, rather than paying for drugs on a per unit basis, you pay a lump
> sum for access to the drug.

Hmm... a system where uncommon but extreme spikes in the cost of care are
artificially distributed so that an entire society can bear them as a group...
that sounds oddly familiar...

~~~
hnzix
_Please put the invisible hands of the market over your ears and wait for the
drugs to trickle down._

Jokes aside - while people are justifiably pointing out the community
healthcare angle, arguably this problem is exacerbated by the American FDA
drug approval model, ie no corporation will fund clinical trials unless
they're guaranteed a profit monopoly.

~~~
cjfd
Actually, there is a market solution to this problem. I cannot claim to have
thought this up, it was discussed in an episode of econtalk. Don't remember
the person that was interviewed.

The idea is that big pharma companies have to publicly post a price for each
of their patents. If anyone is prepared to pay that price they get the patent
for that price. Next there needs to be a tax that is a percentage of the price
of the patent. The money that comes from this tax needs to be funneled back
into healthcare or even better go straight to the ones who are paying for the
particular medicine that the patent protects.

Now the level of innovation can be set by how high the percentage of the tax
is. If the tax is very low healthcare will be expensive but there can be lots
of innovation. If the tax is high healthcare costs will be low but one can
also not expect much innovation.

Of course, there also are some other things that need to be fixed. E.g.,
doctors should not get all of their schooling financed by pharma companies and
so on.

The general idea of such taxes could be applicable to any sort of non-
replacable entity, e.g., it could also apply to land. For one thing, this
would make feudalism regarding land quite impossible, which would generally be
considered a good thing.

~~~
dTal
Why would there be lots more innovation with a low tax? In the limit, that's
the system we have now (0% patent tax, companies are free to price their
patents however they want).

~~~
AmpsterMan
The assumption there is that the current system is already highly innovative
in the U.S., which is generally accepted as true.

~~~
dTal
But the premise of this entire thread is that "With no prospects for profits,
big pharma neglects new infectious diseases".

------
nostromo
Perhaps they’re behaving entirely rationally. Infectious diseases do not kill
that many people compared to cancer in America.

We may have a bad “flu” year this year, with a spike of elderly deaths, but we
have a bad cancer year every year.

~~~
JamesBarney
But we don't really develop "cancer" drugs. We develop a drug that treats
certain type of pancreatic cancer that give the individuals another 3-6 months
to live. But curing an infectious disease can give someone another 40 years.

~~~
refurb
There are several cancer (lymphomas) that were literal death sentences a
decade or two ago, but how have a very high cure rate.

It's not fair to say we don't develop cancer drugs because some, very
difficult to treat cancers, haven't seen as much progress as others.

~~~
dehrmann
Testicular cancer is now very treatable, but before Cisplatin, the prognosis
was pretty grim. I guess to grandparent's comment, we absolutely do develop
chemotherapy drugs, and many don't just buy you six months, they're life-
saving.

~~~
refurb
I unfortunately can't find it, but there was an interesting chart that showed
overall survival in metastatic colorectal cancer.

It covered the last 30 years. Each new therapy improved survival by only 6-12
months, but each new drug was more effective than the last. Over those 30
years, the median survival went from 6 months to over 5 years.

People shouldn't discount incremental improvements because that's often how
medicine progresses.

~~~
DrScump
Cell type is much more relevant to curability than location.

------
foogazi
Are there national laboratories with the capabilities to find a cure?

Is there a NASA equivalent for infectious diseases to launch a covid-19
moonshot?

~~~
cactus2093
The WHO is saying a vaccine is 18 months out, and I’m very curious what that
means. I haven’t seen any detail as to why it takes that long.

It’s short enough that clearly they expect it won’t be very hard, like no one
would say a general cure for cancer is 18 months out. So what is preventing us
from speeding it up more? Why can’t it be made in 6 months, or 3 months? Is
the majority of that 18 months a basic r&d phase of figuring out what will
work? If so, why can’t it be parallelized and sped up with more resources? Is
it time for clinical trials? To ramp up manufacturing? I can’t help thinking
that for a disease that prevents such a big risk to society, there must be
clever ways to speed up the normal process for this kind of thing, perhaps
with some government involvement in funding or coordinating efforts.

~~~
Infinitesimus
> People have been saying a vaccine is 12-18 months out, and I’m very curious
> what that means. I haven’t seen any detail as to why it takes that long.

All the things you said are factors. Clinical trials are one of the biggest
because you have multiple phases to observe to guarantee safety.

It's no use shipping a vaccine in 3 months after a small test and have
everyone die in a year because of a side effect no one waited long enough to
see.

Drug development and safety is a very complex space from what I've learned

~~~
vikramkr
Guaranteeing safety is absolutely a crucial part of it. And if you pull
something out that doesn't work, giving people a false sense of immunity would
also make things worse.

And safety shouldn't be underestimated. The story of dengue vaccine
development is a cautionary tale. The first time you get dengue is usually not
too bad, but it can be deadly if you get it again. Part of that is
hypothesized to be driven by your own immune system, which, once immunized
against one strain, produces antibodies against it in the next infection.
However, if it's a slightly different strain of dengue the second time around,
the antibodies meant to neutralize the disease are believed to make the
disease more virulent instead (antibody-dependent enhancement). The immune
system makes it worse. So when a dengue vaccine that didn't fully immunize
against all strains was developed (not deliberately, people tried to immunize
against all strains but this is a case where less efficacy than expected made
things worse), it didn't make things better. It ended up priming people to get
dengue.

Biology is super weird - even something as "simple" as vaccine development has
a lot of unknown unknowns. And as dengue showed us, it's not just a case of
"it might not work," because it could make things worse. That's why we have to
run these clinical trials and take time to do things right, especially for
something that would be as widely deployed as a coronavirus vaccine.

------
WalterBright
In the 1960s big increases in regulations on new drug development led to big
cost increases, and hence less interest in non-blockbuster treatments.

~~~
refurb
Sure, but as a result we don't have problems like thalidomide popping up every
decade or so. There are benefits (and drawbacks) to having a much more
stringent approval process.

And probably worth adding that in public health emergencies, the FDA is more
than willing to pull back on regulations in the interest of the public good.

~~~
barry-cotter
You can have a stringent safety process without having _any_ efficacy process.
The FDA has no incentive to approve drugs but plenty to deny them so delay is
the order of the day. Delay in approving new effective drugs costs lives.

The FDA has not shown any willingness to pull back on regulations during the
current COVID crisis, nor have they historically shown any such willingness.
Politicians have forced them to. They have _never_ shown any organic
willingness to relax regulations.

~~~
vikramkr
I'm not clear on whether you're arguing that the FDA should not be requiring
efficacy? The FDA makes exceptions on cases of urgent need, and not having
efficacy as a bar would reduce the reward for innovation - why would you spend
all the time and effort to development a treatment for a disease if vitamins
with no efficacy are already filling the market? False hope is dangerous, and
healthcare is uniquely suited to attracting snake oil salesmen with cure-alls
because of how serious health needs are - these regulations are written in
blood

~~~
barry-cotter
The FDA should not require efficacy testing. If it’s safe let patients and
their doctors do what they want. In practice that’s what they do anyway, see
off label prescribing which is around one fifth of all prescriptions in the
US. Removing efficacy testing would double or more the number of new drugs
available.

Fraud is already illegal. Doctors can already be sued for malpractice. Testing
for efficacy makes no sense in a world in which off label prescribing is
routine.

> Assessing the FDA via the Anomaly of Off-Label Drug Prescribing ——————
> ——————

> Once a drug has been approved for some use, the FDA has almost no control
> over how that drug is actually prescribed. The prescribing of drugs for non-
> FDA-approved uses, called “off-label prescribing,” is widespread. Drugs
> prescribed off-label have not met the FDA’s requirements for proving
> efficacy in the off-label applications. The practice of off-label
> prescribing therefore raises interesting questions. Why does the FDA, in
> effect, require that some drugs be tested for efficacy but not others? If
> there are good reasons for the FDA to have strong pre-approval powers
> regarding efficacy, shouldn’t FDA post-approval powers be commensurate?
> Alternatively, if there is good reason for widespread off-label prescribing,
> doesn’t this call into question the FDA’s pre-approval powers?

[https://www.independent.org/publications/tir/article.asp?id=...](https://www.independent.org/publications/tir/article.asp?id=240)

> There are also scientific reasons to replace Phase 3. The reasoning behind
> the Phase 3 requirement — that the average efficacy of a drug is relevant to
> an individual patient — flies in the face of what we now know about drug
> responsiveness. Very few drugs are effective in all individuals. In fact,
> most are not effective in large portions of the population, for reasons that
> we are just beginning to understand.

> It’s much easier to get approval for drugs that are marginally effective in,
> say, half the population than drugs that are very effective in a small
> fraction of patients. This statistical barrier discourages the
> pharmaceutical industry from even beginning to attack diseases, such as
> Parkinson’s, that are likely to have several subtypes, each of which may
> respond to a different drug. These drugs are the underappreciated casualties
> of the Phase 3 requirement; they will never be developed because the risk of
> failure at Phase 3 is simply too great.

[http://www.washingtonpost.com/wp-
dyn/articles/A43257-2003Nov...](http://www.washingtonpost.com/wp-
dyn/articles/A43257-2003Nov14.html)

~~~
vikramkr
Off label use is allowed. Marketing for off label use is absolutely not
allowed. Claims of off label efficacy are not remotely allowed. And the FDA
has post approval powers to revoke approval for drugs not found effective.
Doctor's autonomy leads to off label being allowed, and some of the legal
arguments for it involve freedom of speech, not medical optimality.

Phase 3s already are no longer required, it looks like the article you linked
was written in 2003? That was literally almost 17 years ago when we'd just
barely sequenced the first human genome. There are entire fields of medicine -
precision medicine - that literally address the whole subgroup question.
Companion diagnostics are routine, rare disease approvals are up, plenty of
Huntington trials in progress - that article might as well be about an alien
civilization with how different things are today. Value based pricing,
redefining cancer into separate genetically defined baubgroups and developing
drugs for each, Gene therapy, ... It's no longer easier to get approval of a
drug that's marginally successful in a large population, smaller populations
with large effects make it way easier to see responses. And the 21st century
cures act in 2016 evolved the regulatory landscape even more - it's like
comparing Sputnik with the ISS. Yeah, they're both sattelites, but the field
has come a long way in the time between the two.

------
aschatten
The article mentions the difficulties with clinical trials. It makes sense,
now China running hundreds of studies on coronovirus with thousands of people:
[http://www.chictr.org.cn/searchprojen.aspx?title=&officialna...](http://www.chictr.org.cn/searchprojen.aspx?title=&officialname=&subjectid=&secondaryid=&applier=&studyleader=&ethicalcommitteesanction=&sponsor=&studyailment=coronavirus&studyailmentcode=&studytype=0&studystage=0&studydesign=0&minstudyexecutetime=&maxstudyexecutetime=&recruitmentstatus=0&gender=0&agreetosign=&secsponsor=&regno=&regstatus=0&country=&province=&city=&institution=&institutionlevel=&measure=&intercode=&sourceofspends=&createyear=0&isuploadrf=&whetherpublic=&btngo=btn&verifycode=&page=1)
testing few drugs and their combination at a time, it's hard to do outside of
epidemic.

------
StreamBright
Why are we surprised? If the incentives are not for curing infectious diseases
than they won't do it. For big pharma, the incentives are: keep humans sick as
long as it is physically possible and charge along the way.

------
VvR-Ox
1:0 for Capitalism vs. Humanity.

Exactly this is why the motivation to do at least some things should not be
bound to earning profit.

There is common goods that we need to share, global issues that need to be
addressed together and we need to find ways to achieve this if we want to
develop further as a civilization.

Money must not be the sole reason why we do things or we will fail with this
"strategy" and we need to come up with good ideas for an alternative and try
it.

I know this will probably not make me very popular especially with people
living in the US as their minds are constantly being flooded with the idea
that everything straying from capitalism is socialism and therefor evil. I
will post it nevertheless, down-votes don't hurt and I will write my opinion
until it is censored completely.

~~~
tim333
Not sure 1:0 is accurate scoring. Most of the drugs and medical advances we
have came out of capitalist systems. Not saying that capitalism is perfect or
there shouldn't be government funded labs also.

------
jmartrican
I would imagine living customers and a workforce that is not quarantined would
be reason enough, but hindsight is 20/20\. It would be silly if the offices of
a big pharma company are closed due to an infectious disease that the big
pharma company would have been best suited to tackle but cant due to neglect
in fighting infectious diseases.

------
bionhoward
one way around this is to develop platforms which apply to a range of
diseases. why reinvent some fancy shape of atoms for each disease? it's
entirely possible to develop something which works on cancer and coronavirus.
just look at CRISPR, or RNAi ... master delivery and you can simply re-target
the therapy toward different sequences.

Here
([https://github.com/bionicles/coronavirus](https://github.com/bionicles/coronavirus))
is code to design CRISPR-Cas13 CARVER
([https://www.sciencedirect.com/science/article/pii/S109727651...](https://www.sciencedirect.com/science/article/pii/S1097276519306987?via%3Dihub))
30mer guides against regions of Coronavirus conserved between SARS, MERS,
HKU1, and SARS-nCoV-2 (Covid-19 Virus) and not found in highly expressed Lung
protein-coding RNA. Uses BioPython, Redis SADD/SISMEMBER, and tools from EMBL
(Emboss Consensus and Clustal Omega Alignment) and data from NCBI. The good
news is, it's probably possible to delete Coronavirus genome directly inside
the lungs, without vaccines; just deliver nanoparticles or adenovirus (doesn't
replicate) with an inhaler and express CRISPR-Cas13 and the gRNA using the
Surfactant promoter sequence for lung-only expression of the therapy

disclaimer: I need to work on the readme and write a blog post, but the data
is there and the general core works. There's ~30k guides possible and 226
target 13 longest conserved regions across 4 different outbreaks spanning 17
years of virus evolution (provides reasonable confidence these regions are
necessary for the virus to function)

If anyone knows some folks in the Pharma / Biotech industry I could use help
to run the tests on this, tell em to email bion at bitpharma.com

edit: readme improved. currently looking for promoter consensus sequences for
lung (surfactant protein TFs like TTF-1)

------
block_dagger
With the amount of economic upheaval from the coronavirus scare, I fail to see
how there are no prospects for profit.

~~~
alephnan
Creating value is one part, capturing it is another

~~~
csallen
Not sure why people are downvoting you. It's clearly the case that there are
lots of problems you can solve that create value and make/save people money,
yet don't result in you capturing any of that money for yourself. For-profit
companies mostly ignore those kinds of problems by definition.

------
daenz
"Neglects" implies that they're ignoring their responsibilities. How is this
the case?

------
pkaye
I think governments should take charge in this. Look at how much the
development of the ebola vaccine bounced around for years.
[https://www.statnews.com/2020/01/07/inside-story-
scientists-...](https://www.statnews.com/2020/01/07/inside-story-scientists-
produced-world-first-ebola-vaccine/)

------
crimsonalucard
If commercial incentive isn't viable then the incentive needs to change. Think
of it like the military but as a medical industrial complex.

------
magwa101
The market does not solve everything, but it does create everything. Therefore
we are evolving into pure consumerism.

------
chapium
This is the part where public corporations come in.

------
ThomPete
The opportunity is a generalized approach to solving these diseases which i
think we are getting to finally. Thats the true promise of digital technology.

Thats how incentives gets aligned.

------
zachguo
Since COVID-19 is targeting elders, I can imagine there are evil capitalists
or bureaucrats who view this pandemic as a gigantic economic stimulus for the
next decade. Sorry for my evil thought.

~~~
bocklund
The price of the Wirecutter’s #1 recommended forehead/ear thermometer on
Amazon has changed from $30 between 2016 and February 2020 to $100 since
February.

[https://camelcamelcamel.com/iProven-Thermometer-Temporal-
For...](https://camelcamelcamel.com/iProven-Thermometer-Temporal-Forehead-
Function/product/B01H3MTVE8)

------
dfsegoat
...as they develop a vaccine for Ebola.

[https://en.m.wikipedia.org/wiki/Ebola_vaccine](https://en.m.wikipedia.org/wiki/Ebola_vaccine)

------
m0zg
How can you target "new" infectious diseases if they are really "new" every
year other than by guessing the right vaccine (as they do e.g. for the flu)? I
mean, what worked for SARS won't necessarily work for COVID19, even though
it's also a subvariant of SARS. If this is the case, by the time you come up
with a drug and take it through all the (extremely costly) stages of testing
approval, it'll be too late already, and herd immunity would have obviated the
need for what you've just invested billions and countless person-years into.

~~~
RandomWorker
You can monitor existing viruses in wild animal populations and give them
treatment before it mutates and goes to humans. This would be relatively cheap
compared to solving the problem afterwards. We now know that bats are prime
suspects for carriers of these diseases because they them selves don’t get
sick much from them, live is close quarters, fly and are mammals.

~~~
Broken_Hippo
You'd be wasting money, though, and not necessarily saving money. Most animal
diseases do not cross over to humans and IIRC, most of them that have crossed
over come from farm animals. More people live in close contact with farm
animals than they do things like bats.

This effort would honestly be better spent working on things humans already
have.

------
marricks
Maybe there’s just some things that are common good and should be publicly
funded rather then gambling on capitalism to solve it

------
blackrock
So there you have it.

Late Stage Capitalism Failure.

No ability to make a bajillion dollars in rent-seeking profit. So F it! Let
the people die.

~~~
Mirioron
Well, if capitalism is the problem, then why don't the socialist/communist
countries develop the drug instead? Or alternatively, the community could come
together and they could work on coming up with the treatment as a group. But
we all know that neither of these are likely to happen. Researchers need money
to live, labs need money to run.

~~~
VvR-Ox
Because there is no such countries until someone can prove otherwise (which
will not happen because they don't exist).

Big capital put this idea inside the heads of many people living in the West
and until today they really believe there is countries who are
socialist/communist. Neither the GDR nor the UDSSR or China are examples for
countries like that and people who know about politics, economy and society
know this as a fact.

It is easy for you to criticize all alternatives at once because you have
never seen any and chose to believe what the ruling party (=capitalism) makes
you believe.

~~~
ros65536
The classic no true communist country fallacy. Have you considered that no
such country exists because it is impossible, vecause it so quickly devolves
into socialist hell like in USSR, north korea?

------
Der_Einzige
Sounds like a good time for capital N nationalization! :)

------
perl4ever
I thought the "party line" was that private industry doesn't accomplish much
if anything, so isn't "big pharma" irrelevant? It makes more sense to demand
higher taxes and more basic research.

~~~
lazyier
The problem is that regulation is so expensive there isn't any financial
motivation in researching does that are unlikely to generate massive revenue.

The reason for this is FDA is fundamentally extremely conservative. The people
that run the regulatory system are just faceless bureaucrats and are risk
adverse. Their pay is based on seniority and there isn't any financial
motivation for them to take risks or stand out. FDA is nothing more then a
collection of individuals so the motivation of the agency is a mirror image of
the motivations of the people running it.

To put it bluntly:

When diseases like cancer or influenza or <insert name of any disease> kill
people the diseases get blamed. But if a drug makes to it market and ends up
maiming people or killing them then the FDA gets blamed.

So from the FDA's perspective it's much more important that we have ultra-safe
drugs then it is to have new drugs to cure and treat diseases.

The regulators are going to take the default position that more testing and
screening and expenses are good. While allowing consumers and doctors to take
risks to treat diseases is bad. And over the decades it has just gotten more
and more and more and more expensive to get the drugs out to the public.

And since it's too expensive to make new drug companies because of the
regulators then you will never see any smaller nimble companies come in and
compete with them and force the big companies to behave themselves.

This is why you see all the generic drugs being bought up in the past couple
decades. During the Obama administration they signed regulatory changes that
rose the cost of validating generic drugs considerably. It wasn't so expensive
that it would drive generics from the market, but it's expensive enough that
you can't make new generic drug companies. So the big name brand drug
companies just buys them all up. And because of that they no longer face
competition from generics. They own both the name brands and the generics.

If it was cheaper to make generic drug companies this approach wouldn't work.
People would make new companies for the sole purpose of getting bought. It
would make buying companies up to kill competition unsustainable.

I've worked in heavily regulated industries before and it's a pretty obvious
pattern. Regulators regulate. Costs go up. Competition goes down. And then the
big companies become isolated from competition because it's just too expensive
to compete with them. Then the government has to bend over backwards to ensure
the profitability of these dominate corporations because if they were to go
out of business there would never be any replacements.

It's a form of market lock-in. Over regulation effectively becomes a license
for these big pharma companies to do pretty much whatever the fuck they want.
They love it.

~~~
perl4ever
I think people who talk about "over regulation" should be excluded from
serious discussion. "More" or "less" or "no" regulation is never the answer.

I don't think we have ultra safe drugs. I could be just paranoid, but I don't
think the FDA is that good at monitoring the manufacturing of drugs. And I
know I've read about how sometimes they approved a new dosage without actual
testing and it turned out in at least one case the delivery mechanics didn't
work properly.

Deregulation is like reform. Enough people think it's automatically good, that
it's completely meaningless, and because it's meaningless the worst people
pick it up as a slogan and run with it.

As someone that could really benefit from new drug approvals, I don't see
deregulation as my savior because if it's executed by the worst people, then
it will just lead to more snake oil and less ability to differentiate.

------
beardedman
What a pile of sensationalist rubbish.

In 2018 we had an estimated 400k people dying of Malaria [1] & around 600k
(est.) people dying of cancer in the US alone. [2] Compare that to the 3110
deaths that have happened in the last 3 or so months for COVID-19. [3]

I think a little perspective would go a long way here.

[1] [https://www.who.int/news-room/feature-
stories/detail/world-m...](https://www.who.int/news-room/feature-
stories/detail/world-malaria-report-2019)

[2] [https://www.cancer.org/research/cancer-facts-
statistics/all-...](https://www.cancer.org/research/cancer-facts-
statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html)

[3] [https://www.who.int/dg/speeches/detail/who-director-
general-...](https://www.who.int/dg/speeches/detail/who-director-general-s-
opening-remarks-at-the-media-briefing-on-covid-19---3-march-2020)

~~~
jokowueu
Covid if not put under control will effect every one everywhere (unlike
malaria) . Imagine a 1% fatality on the human population but at a repetitive
rate .

~~~
beardedman
That 1% is still to be confirmed. We don't know the mortality rate yet.

