
Biopharma has abandoned antibiotic development - refurb
https://endpts.com/biopharma-has-abandoned-antibiotic-development-heres-why-we-did-too/
======
jdkee
From the article, "Public measures designed to incentivize development of new
antibiotics are woefully inadequate."

This is the issue. Relying on private entities to provide (R&D, clinical
trials) for what are ostensibly public goods (antibiotic resistant bugs puts
every person at risk) brings the real risk of market failure.

The NIH is making some progress on this front.

[https://aspe.hhs.gov/system/files/pdf/258516/ProgressYears1a...](https://aspe.hhs.gov/system/files/pdf/258516/ProgressYears1and2CARBNationalActionPlan.pdf)

It appears that overprescribing existing antibiotics to people and livestock
is a leading cause of rising drug resistance, both of which can be addressed
by policy changes.

~~~
iambateman
It seems like overprescribing to a cow is such low hanging fruit.

I understand that if my 5-day-old child marginally needs antibiotics, that the
doctor may prescribe to appear active.

But couldn’t sensible legislation end over-prescription to livestock
overnight? Is this really an issue of beating the cow lobby?

~~~
dv_dt
The "cow lobby" is large multinational corporations... so yes it's an issue
beating their lobbyists. Also, a side effect of antibiotics is weight gain in
livestock - so even legislation that ostensibly outlaws use for the direct
purpose of directly adding to profits, language in regulation is generally
kept for medical purposes of "reducing disease" among herds. Disease that is
at a high rate because of high density feedlot practices...

~~~
killjoywashere
> a side effect of antibiotics is weight gain in livestock

Original article in Nature:
[https://www.nature.com/articles/nature11400](https://www.nature.com/articles/nature11400)

~~~
dv_dt
There have been quantitative calculations for antibiotics taught for years in
ag departments, and known among industry practitioners. Farming is a highly
quantitative industry, and any agent of growth promotion is tracked carefully
along with feed energy & cost inputs. Today you may have to go back to older
documents to see talk about it in a more open manner though.

Here's a more industrial type of analysis paper (2003)

[https://www.cambridge.org/core/journals/journal-of-
agricultu...](https://www.cambridge.org/core/journals/journal-of-agricultural-
and-applied-economics/article/productivity-and-economic-effects-of-
antibiotics-used-for-growth-promotion-in-us-pork-
production/63959BF885FCE4C2E8C55BBFF566F8F5)

------
DoreenMichele
A reminder: Poor sanitation in underdeveloped countries is part of what is
breeding antibiotic resistant infections which then get exported to more
developed countries thanks to the modern ability to get from pretty much
anywhere on the planet to pretty much anywhere else on the planet that people
typically reside in about 24 hours (or less).

The last time I said this, someone apparently thought I was being racist and
classist and saying mean things about "those people" overseas. I'm not.

I'm saying there are other ways to tackle this issue and one is by supporting
hygiene programs worldwide, including here in the US when the revival of
sometimes deadly _Medieval Diseases_ is associated with the homeless crisis we
are having.

~~~
quotemstr
> Poor sanitation in underdeveloped countries

It's not just poor sanitation. It's that in underdeveloped countries
antibiotics are completely uncontrolled, available without a prescription for
almost nothing. This availability promotes misuse.

~~~
zozbot234
Better sanitation and hygiene would help with that as well, though. People
would no longer get sick with lots of infections that can easily be prevented
in other ways, and the habit of overprescribing antibiotics would disappear.

~~~
quotemstr
People take antibiotics prophylactically all the time even here in the US.
They'll do so in the developing world too unless stopped with regulation
restricting use of antibiotics to cases where they'll be effective.

------
sithadmin
>Achaogen ($AKAO) and Paratek ($PRTK) both had NDAs approved for novel
antibiotics and saw their stock prices drop sharply in response to the news,
as investors anticipated all those pesky expenses related to
commercialization.

I was around for most of Achaogen's implosion. Some key points not mentioned
in this blog post:

1.) In the ~12 months leading up to FDA approval, Achaogen started burning
their capital at a rate that was, frankly, insane. Financial decision-makers
were definitely counting their chickens before they hatched, and this
ultimately seems to have resulted in massive cuts to opex (e.g. sales
positions) that snowballed into abysmal revenue once Zemdri hit the market.

2.) The FDA approved Achaogen's product, Zemdri, indication for complex UTIs
(cUTI), but not for bloodstream infections (BSI). The latter indication is
much more lucrative. My personal opinion is that this factor alone wasn't
responsible for the poor sales numbers, but it was certainly a huge
contributor to the problem.

------
LatteLazy
There's no guarantee that there even are further broad spectrum antibiotics
possible.

As far as I understand, what's needed here is (first) fundamental research,
then discussion of promising ideas, then maybe you can rely on private
companies to perfect and bring to market new molecules.

Thats a far cry from other drugs for other diseases where there is a futile
set of fundamentals to pick over and small research groups spinning off from
universities regulatly.

Every time I've heard of new prospects, it's either been reexamining old
methods (like plagues) or new fundamental work (sampling and sequencing new
bacteria, studies on fungi).

So instead of "incentives", we should just man up and fund some biology and
stop wasting what we have already on farm animal fattening programs and the
worried well etc.

------
xupybd
If the public knew about this problem, if it were marketed to them there might
be a solution. You'd likely need some policy changes too. But if I could
choose between an insurance that supported and supplied new antibiotics I'd
jump at that insurance over one that did not. I'd happily pay more to be
covered for something so fundamental.

Obviously there would be a lot to iron out but I think there is an opportunity
for health insurance companies to make a good amount of money off of that.

I'm guessing however that existing policy would make this impossible.

------
rshnotsecure
So much of the modern corporation has been outsourced...including nearly all
research. Most animal research today and Phase II trials are done...in
China/India.

The evidence that these studies are largely faked due to the pressure put on
the staff and management there has been piling up for years. I would recommend
“Science Mart: Privatizing American Science” by Philip Mirowski for more on
this.

------
dmix
> and that larger players would correspondingly re-enter the market, hungry to
> pick up first-in-class antibiotic programs.

Does this mean their business model is basically always going to be getting
acquired by one of the big pharma firms?

~~~
s1artibartfast
Yes, This is essentially the only model in Pharma and bio-med.

------
ggm
Public fund, public production. Take antibiotics research out of the IPR
domain, and put it back into public health funding.

------
sddfd
Tldr: privately funded research is not working.

I don't understand why antibiotics research can't be done at (publicly funded)
universities?

~~~
zozbot234
It's comparatively difficult to do applied research with _grant_ funding,
which is what most "publicly funded" universities tend to rely on. For this
sort of high-value research, what you want is _prizes_ so that success can be
rewarded after the fact, even when the usual "market" mechanism of selling
drugs is not working very well for whatever reason. Current policy approaches
provide 'development incentives' of some sort as OP mentions, but clearly
these are not enough.

~~~
dv_dt
Or crazy thought, expand the number and duration of grants to research this
area...

~~~
kryptiskt
You can't rely on researchers to make a product out of their findings (running
trials and getting approval) and that's were the big costs are.

~~~
mattkrause
Not in the current job climate, but if (say) successfully shepherding
something through FDA approval were treated like a Nature paper, I bet you'd
see a lot more researchers trying it.

The problem with the prize idea is that this stuff is _expensive._ Most
academic institutions don't have a mechanism for doing something "on credit"
and hoping to win a prize that covers the costs and then some. Some companies
can, but the optics of giving prizes to BigPharma also aren't great.

~~~
zozbot234
> Most academic institutions don't have a mechanism for doing something "on
> credit" and hoping to win a prize that covers the costs and then some.

Some do, actually. It's called an "endowment". Unless by mechanism you meant
an internal _policy_ to allow for this - but that's the sort of stuff that can
be changed with relative ease.

~~~
mattkrause
I chuckled a little at "relative ease" (nothing involving university legal
stuff is easy) but ran some numbers to see how feasible that would be.

The median Phase II trial costs about $10M and has a 30% success rate; Phase
III costs a lot more (say 2x that), but has better odds (58% advance to
approval, and 85% of those get approved). Neglecting Phase I and everything
before it, the expected cost is therefore about $16M (over ~3 years) and gets
you an approved drug 15% of the time.

There are only 11 individual universities (plus three university systems) with
endowments over $10B, but a surprising number with endowments in the $1B
range. The draw rate on endowments is usually capped at 5% so that the
principal remains intact, giving you around $50M for the entire university's
endowment income.

A single trial would therefore consume about 10% of the endowment income per
year--and with a 15% success rate, it's probably not going to win anything.
There's no way a university president is going to let a group of researchers
make a gamble like that.

------
heavyset_go
The healthcare and pharmaceutical industries sure seem to have a lot of market
failures.

------
AtlasBarfed
A typical failing of short term economic thinking:

Superbugs are virtually certain to kill a huge number of people, because
virulent resistant strains gonna Black Death.

But we can't get a payoff within a quarter or whatever the payoff window for
the seed money is? Eh, don't bother investing.

This is where the government must step in. Oh right, gubberment baaaad.

Seriously, if these have promise they should be funded for 10 years by a
multinational conglomerate.

I mean, maybe the Chinese government will step in. You know, the only forward-
thinking major government in the world? What a world.

~~~
refurb
You're missing the main point of the article.

If you invent a great new antibiotic, it won't be used unless absolutely
necessary.

~~~
ur-whale
This is a great summary of the article and should be the top comment.

------
Starkus
Ah, reminds me of investing (poorly) in Amplify Biosciences in late 2017...

Since acquired by Armata pharma, which trades around 4 a share, cap of 40M....
I lost 90% of my investment, oh darn, was a bad investment in hindsight.

Looking at that chart in the article, not too surprised the rest of the market
in big red territory.

------
tomohawk
> Un­der the Af­ford­able Care Act, hos­pi­tals must pay a penal­ty for each
> hos­pi­tal-ac­quired-in­fec­tion (HAI) oc­cur­ring with­in their in-pa­tient
> pop­u­la­tion. As a re­sult, if a pa­tient dies from a su­per­bug
> con­tract­ed dur­ing a pro­ce­dure such as surgery, the of­fi­cial cause of
> death may be in­stead list­ed as “Com­pli­ca­tions from Surgery.”
> Con­sis­tent and sys­temic un­der­count­ing of ill­ness­es and deaths from
> re­sis­tant in­fec­tions fur­ther dis­cour­ages the de­vel­op­ment of new
> an­tibi­otics as the num­ber of pa­tients who need these med­i­cines may
> ap­pear to be very small.

Sounds like the regulatory environment is overriding any market forces or
customer needs.

~~~
crooked-v
> Con­sis­tent and sys­temic un­der­count­ing of ill­ness­es and deaths from
> re­sis­tant in­fec­tions

That's not "regulatory environment goes too far", that's "regulatory
environment doesn't go far enough".

~~~
quotemstr
Pick _any_ problem that regulation causes and you'll find some people saying
that the real problem is that the regulation doesn't go far enough. You can
listen to these people and expand regulation an indefinite number of times
until you end up with a full command economy --- and we all know how well
command economies work.

~~~
xupybd
Poorly crafted regulation tends to cause more harm than good. That's why
turning to regulation as the solution must be done with care.

On the other side. Unrestrained markets tend to do more harm than good. That's
why turning away from regulation must be done with care.

