Emeritus Prof Christopher MayJan 5, 2025

While its not really news, warning about the antibiotic crisis continue to be voiced, while at the same time our (the world's) addiction to over-deploying them goes on.

It may be too late to halt the rise of antibiotic resistant strains of infection & it seems likely we may be about to plunge back into C19th rates of mortality from diseases & medical interventions;

yet one more aspect of our lives where we are moving backwards not forwards.

#antibiotics #health
https://www.theguardian.com/society/2025/jan/05/antibiotic-emergency-could-claim-40-million-lives-in-next-25-years

Antibiotic emergency ‘could claim 40 million lives in next 25 years’

As superbugs spread across the globe, death rates from antimicrobial resistance are set to double, says England’s former chief medical officer

The Guardian
Show threadMarjorieRJan 5, 2025

@ChrisMayLA6 as well as misuse of antibiotics there is a big problem on that there is currently no money for big pharma in developing new ones.

From the article:

"The ease with which AMR spreads means it is becoming more and more important that we do not misuse the antibiotics we possess. It also generates a need for new antibiotics to be developed - and again this raise problems, said Davies.

'We’ve had no new classes of antibiotics come into routine use since the late 80s and the market model that would promote the creation of new ones is broken. If you develop a new antibiotic, it might be used by someone for a weekly course once a year. Where’s the profit in that?'

'By contrast, blood pressure drugs that have to be taken every day, or cancer drugs that have to be administered for months, offer pharmaceuticals far greater profits. So there is no incentive for them to try to develop new antibiotics. It is a real headache.'

The problems that lie ahead in dealing with AMR are not insurmountable, Davies insists, but they must be addressed with an increased sense of urgency. The G7 forum of industrialised nations has at least recognised the crisis. However, there is still a lack of adequate action and that needs to be tackled as an imperative in the coming year, she insists."

Again Government funding needed?
And for goodness sake if we do that reserve the patent rights.

Show threadTC Won't Give In To LiesJan 5, 2025

@marjolica @ChrisMayLA6

Gosh, it's almost like allowing medicines to be developed by for-profit companies has only produced the most profitable, not most useful, drugs.

Eric PyrrhusJan 5, 2025
Show threadMike Malaska

@TCatInReality @marjolica @ChrisMayLA6 Former medicinal chemist here.

Developing drugs is really hard. We have a 96% failure rate.

Here is some math.
Assume $300K FTE rate per scientist.

Find a preclinical candidate: $15M
Tox testing: $5M

Phase 1 clinical trials (safety in healthy subjects - is it safe?): $50M

Phase 2 clinical trails (efficacy in diseased subjects - does it work?): $250M

Phase 3 clinical trials (liability): $300M

Total: $620M if everything works.

But, 96% failure rate.

Jan 5, 2025 at 5:16pmWeb
Show threadMike MalaskaJan 5, 2025

@TCatInReality @marjolica @ChrisMayLA6 (those are very old numbers, btw. Prolly double now.)

At each step, about 50% attrition.
(This is why press releases finding something active #InMice is so silly.)

So it COSTS $620 million to find a new drug if everything works.

How much do pharma companies actually SPEND to find a new drug?
(So include failure costs)

Turns out about $8B per drug.
(Reported R&D costs per new drug approval)

Show threadMike MalaskaJan 5, 2025

@TCatInReality @marjolica @ChrisMayLA6

So, if you want new antibiotics, someone's gotta:

1) pony up a several BILLION dollars of dedicated R&D effort for just this.

2) find some way to improve that 96% failure rate.

That 96% is ingrained in every pharma scientists brain. Keeps us humble. There is always a "bold new paradigm to accelerate drug discovery" that never moves the needle.

Show threadMike MalaskaJan 5, 2025

@TCatInReality @marjolica @ChrisMayLA6
...the other implication is that you gotta make up for that initial cash outlay on the back end.

So assume 16 years of exclusive patent period and average during that period of 50% market penetration you need to have a $1B per year drug to make up for your initial costs.

Big question: Is there a $1B per year driving need RIGHT NOW for a new antibiotic?

(Remember, there are other generic antibiotics, insurance companies will want to try those first.)

Show threadMike MalaskaJan 5, 2025

@TCatInReality @marjolica @ChrisMayLA6

One of my favorite quotes in the lab:
"Ya know, our job is discover new treatments insurance companies don't want to pay for."

Show threadEmeritus Prof Christopher MayJan 5, 2025

@mike_malaska @TCatInReality @marjolica

How does this relate to pubic sector research, or are your figures inclusive of that cost?

Show threadHilaryJan 5, 2025

@ChrisMayLA6 @mike_malaska @TCatInReality @marjolica

Public sector research doesn't go further than possibly suggesting a pre-clinical candidate drug. All the expertise in developing from there on is in the private sector.

Show threadEmeritus Prof Christopher MayJan 5, 2025

@regordane @mike_malaska @TCatInReality @marjolica

So the private sector expertise in development of delivery & scaling?

Show threadHilaryJan 5, 2025

@ChrisMayLA6 @mike_malaska @TCatInReality @marjolica

Um yes, no. Formulation, manufacturing, pharmokinetics, trials, regulatory compliance.

Yeah, you could call that delivery and scaling. But I think that comes across as a bit demeaning compared to what's actually involved.

Show threadEmeritus Prof Christopher MayJan 5, 2025

@regordane @mike_malaska @TCatInReality @marjolica

Apologies; it wasn't meant to be demeaning but rather a quick way for me thinking about the division of labour in development; I always assumed the patent protection demanded by Big Pharma was to cover the (and again you'll likely not like the phrase) commercialisation phase.

My Q. was always whether patent(s) was the best vehicle for that phase of the process.... in social terms (rather than profit terms)

Show threadMike MalaskaJan 5, 2025

@ChrisMayLA6 @regordane @TCatInReality @marjolica This is a really great question.

Patent protection incentivizes research and competition. There needs to be reward for the effort. Maybe some way to publicly defray clinical trial costs?

But patent system does obscure research. Limits transparency.

(You have to release some data in a patent to show utility. I once spent a full day determining what data we could release that would decoy away from our active molecule.)

Dunno. Good discussion.

Show threadHilaryJan 5, 2025

@mike_malaska @ChrisMayLA6 @TCatInReality @marjolica

Yeah. I agree. I've no expertise in patents but it's clear that they're not always a sufficient incentive to stimulate socially desirable innovation.

IAVI was a case in point (vaccines tend not to be profitable) - it operated as both a public/philanthropic/non-profit early-phase pharmco and a policy unit. In the latter role, promoting alternative incentives such as advance purchase/price guarantees.

Show threadMike MalaskaJan 5, 2025

@ChrisMayLA6 @TCatInReality @marjolica Costs for clinical trials should be the same for either private or public sector.

I honestly don't know what drives clinical costs. I've always assumed it is the personnell costs of record-keeping, administration developing protocols, dealing with Investigational Revew Boards, etc.

(I also dont have a good handle on R&D costs spent vs. drugs approved for public sector efforts. Any ideas?)

Show threadHilaryJan 5, 2025

@mike_malaska @ChrisMayLA6 @TCatInReality @marjolica

Nearly thirty years ago I was doing policy work around how to incentivise development of an HIV vaccine. No longer needed nor important because drugs work...

But while you're coming at this question from below, as a medical chemist, I'm coming at it from above as a policy person.

I'm a bit out of touch and out of date, but yeah, costs for clinical trials are much the same. But the public sector mostly doesn't sponsor trials...

Show threadHilaryJan 5, 2025

@mike_malaska @ChrisMayLA6 @TCatInReality @marjolica

As well as stuff you've said, getting from a preclinical candidate to an actual drug also requires work on formulation. From a molecule, to something that's reasonably stable and can be taken and absorbed by mouth (preferably) or injected.

And pharmacokinetics/dosing - once a day is best. More than twice is problematic beyond the short term.

Show threadHilaryJan 5, 2025

@mike_malaska @ChrisMayLA6 @TCatInReality @marjolica

On Mastodon, there's a lot of IT folks used to the IT development cycle... which is release early in beta, test in the field, improve, maybe end up with a useable product.

Pharma is not like that. It is HIGHLY regulated. You can't just release a product. Even to test a product in humans involves vast compliance and regulatory costs, to show that safety precautions have been observed. For good reasons.

Show threadHilaryJan 5, 2025

@mike_malaska @ChrisMayLA6 @TCatInReality @marjolica

There is a trope one often sees, along the lines of "Drug/vaccine X was invented by publicly funded scientists at the University of Y, so why is Pharmco Z making a profit out of it?"

Yeah, well, I am a socialist too. But the reason that Z is making a profit is that at least 95% of the development cost of getting from the thing invented at Y to something that's useable in real life was borne by Z's shareholders.

Show threadHilaryJan 5, 2025

@mike_malaska @ChrisMayLA6 @TCatInReality @marjolica

New antibiotics will not be profitable. There are different possible ways in which for-profit pharmaceutical companies could be incentivised to support their development.

But without such incentives, there will be no new antibiotics.

Show threadMike MalaskaJan 5, 2025

@regordane @ChrisMayLA6 @TCatInReality @marjolica
Hilarious! One of the projects I worked on as an intern was developing haptens for an HIV vaccine. If it had worked, timing would have taken advantage of your policies.

(This was in mid-80's. It did not work and project abandoned.)

Show threadHilaryJan 5, 2025

@mike_malaska @ChrisMayLA6 @TCatInReality @marjolica

I was the UK policy officer for the International AIDS Vaccine Alliance in 2005 (the year matters because the UK held both the G7 and EU presidencies). That's how I learnt most of this stuff.

And one of the things I learnt was that IAVI's PROUDEST boast at the time was that it had STOPPED a line of research. This being evidence that it was working as it should, acting like a pharmco, except publicly/philanthropically financed.

Show threadHilaryJan 5, 2025

@mike_malaska @ChrisMayLA6 @TCatInReality @marjolica

The public sector mostly doesn't sponsor clinical trials.

Just to add, a brilliant exception is the MRC Clinical Trials Unit at UCL. They do trials that pharmcos won't, often because the drugs are already licensed, eg: Is there a better way to use this? Does it work for prevention as well as treatment? How should it be combined with other drugs?

Before I retired, I worked a lot with these folks. They're great.

https://www.mrcctu.ucl.ac.uk/

Home | MRC Clinical Trials Unit at UCL

MRC Clinical Trials Unit at UCL
Show threadKee HinckleyJan 6, 2025
@mike_malaska @TCatInReality @marjolica @ChrisMayLA6 Are there things the government could do to reduce the testing costs?
Show threadMike MalaskaJan 6, 2025

@nazgul @TCatInReality @marjolica @ChrisMayLA6

Great question! I'm wondering if limiting liability could be a part of it. Requiring all clinical data to become publicly accessible, even for failed trials. (Means a competitor could datamine and scoop out a use.)

Show threadMike MalaskaJan 6, 2025

@nazgul @TCatInReality @marjolica @ChrisMayLA6

One thing that would REALLY help would be limiting liability on combination therapies. (especially in cancer) Suppose Company A has a great blocker for pathway Y and Company B has a great blocker for pathway Z, the combo might work great!

But suppose a combo is tried and a patient dies, who is responsible? Company A? Or Company B? Neither company wants to take on the liability for another. So some potentially useful combinations are not tested.

Show threadCyJan 5, 2025
That's why private research is stupid. You can't make a profit on it. There's just no way. Your boss can't ask "When are you going to be finished discovering?" Research can only be funded by the public, for the common good. It's madness to do otherwise. To make a profit on private research you'd have to oh, I dunno, plunge us into a totalitarian police state so your cop thugs can shake us down and steal our money for you, to make up for the fact that you were dumb enough to expect a profit from research.

Er, if "you" were a pharmaceutical company, that is.

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