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Clinical failure rates over the decades: yikes

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Re: Clinical failure rates over the decades: yikes

#141

Post by jleyank »

refurb wrote: post #98
bonsai_spool wrote: post #78

Earlier quoted context omitted.

This is very facile thinking - are there any examples of a-e in the real world (namely, a brand new drug program was spun up to exploit a-e) ? I think not, which is why I asked the question.

Look at the GLP-1s. Lilly spent tens hundreds of millions developing an oral version that was otherwise the same as the injectable’s. And the notorious inhaled insulin that Pfizer launch (and horribly failed). There are many ways to differentiate drugs, not just efficacy.

Novo Nordisk was first to market with a pill-form for GLP-1 as I recall.

Re: Clinical failure rates over the decades: yikes

#142

Post by ethbr1 »

pinkmuffinere wrote: post #138
ethbr1 wrote: post #132

Earlier quoted context omitted.

Phase I testing is ~$5M. Phase II $6-20M. Phase III is $10-50M. https://pubmed.ncbi.nlm.nih.gov/26908540/ (up to 2012 numbers, non-inflation-adjusted) Those costs are strictly for the mandatory testing, not the precursor drug design, etc. The cost and calendar time required to be sunk before 10% pay off is why you generally only have drug development done by (a) some of the largest corporations in the world or (b) fl…

tl;dr -- Boom's iterations are very similar to a phase III trial! Please prove me wrong! Just to clarify, I think our numbers are in agreement here. From your numbers, phase I + II + III would be in the range $21-75M, all told. Let's double that to account for inflation (2012 is quite stale), to get $42-150M. In California, I'm going to estimate a "normal" engineer's compensation is $150-400k, and the company actuall…

The difference is that phased safety/efficacy trial costs are sunk.

If it fails, you've produced near $0 value, aside from some more information (maybe) about how something doesn't work. Because those costs are strictly for the execution of the trial, not for the development work before/during/after it.

That's in contrast to your hardware prototyping example, where a failed prototype still usually represents >$0 development value.

The appropriate analogy would be if every time a hardware prototype failed testing, it was required by regulation to scrap it, go back to the design stage, and restart from there.

Re: Clinical failure rates over the decades: yikes

#143

Post by a_bonobo »

ip26 wrote: post #104
a_bonobo wrote: post #26

Earlier quoted context omitted.

I actually do this for a living within pharma now! There's a TON of work that goes into drug discovery before we even call it a program. The odds of success are low, so we put in months of work evaluating a candidate before even have a hunch of a program. Yes, the science advances, previously high-hanging fruits become low-hanging become high-hanging again [1], but the tooling also advances: we now have databases lik…

Is public perception the greater problem, or delivery? My outsider read has been relatively few diseases can be targeted right now due to payload delivery obstacles

Yes, getting the drug into the right cell or tissue is still largely unsolved (kidney is easier than brain, of course). But the investors we talk with have dropped all interest in gene editing, too risky. RNA-based technologies are great, though - ASOs, siRNAs etc. Investors are very happy with those :)

Re: Clinical failure rates over the decades: yikes

#144

Post by a_bonobo »

pmarreck wrote: post #115
a_bonobo wrote: post #26

Earlier quoted context omitted.

I actually do this for a living within pharma now! There's a TON of work that goes into drug discovery before we even call it a program. The odds of success are low, so we put in months of work evaluating a candidate before even have a hunch of a program. Yes, the science advances, previously high-hanging fruits become low-hanging become high-hanging again [1], but the tooling also advances: we now have databases lik…

Out of employable curiosity, is there anything that pharma might need help with in terms of coding, pattern-matching, AI assistance, reproducibility, determinism, software controls, ETL, reliable workflow design, or simple IT advice?

Depends in which country you are! IT advice is handled by your regular IT service companies. AI assistance is going gangbusters, as evidenced by Anthropic hiring biologists left and right, places like Isomorphic Labs and Xaira have huge valuations.

Re: Clinical failure rates over the decades: yikes

#145

Post by pmarreck »

a_bonobo wrote: post #144
pmarreck wrote: post #115

Earlier quoted context omitted.

Out of employable curiosity, is there anything that pharma might need help with in terms of coding, pattern-matching, AI assistance, reproducibility, determinism, software controls, ETL, reliable workflow design, or simple IT advice?

Depends in which country you are! IT advice is handled by your regular IT service companies. AI assistance is going gangbusters, as evidenced by Anthropic hiring biologists left and right, places like Isomorphic Labs and Xaira have huge valuations.

I live in the NYC vicinity (about an hour away by car, less by train, on Long Island)

Re: Clinical failure rates over the decades: yikes

#146

Post by halperter »

roenxi wrote: post #28
halperter wrote: post #23

Earlier quoted context omitted.

Rather notably, companies are profit-driven, not good-for-society driven. If 99% of your attempts which cost millions to do fail, the company either has to raise the prices of the drug insanely high or not work as a company. In addition, most drugs aren't humanity saving or crucial for humans to live. You could solve all forms of cancer tomorrow, which would be a great thing, but you aren't "saving humanity". You add…

Lowe mentions costs 0 times though, he isn't making an economic argument. If you want to make an economic argument then 90% is probably the consensus on what is optimal given that is what people are doing. > If this try or die mentality does work, why don't we try every possible amino acid chain in every configuration possible? You tell me. If someone wants to start working through the amino acids one by one I'm not…

I mean, economics is pretty important for a business, no? The issue with the idealistic "do everything we can" is that we have limits. Money is one of the most, if not _the_ most important parts. When clinical trials take tens of millions to do, it is economically infeasible to try things at random; there needs to be an informed approach. I can see why you call my argument about cancer a strawman, and I'd like to clarify that as a general concept, just because humanity could survive for a few more centuries (paraphrased), we can't just be trying randomly. The person who randomly creates protiens that have a _miniscule_ chance to cure an important disease would be much better off putting their efforts into not just guessing and checking.

TLDR: I just have an issue with their "we should try every combination with no regards to constraining factors" approach

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