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Developing a cancer drug without Big Pharma: this hospital shows it can be done

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Re: Developing a cancer drug without Big Pharma: this hospital shows it can be done

#151

Post by nkrisc »

InDubioProRubio wrote: post #148
nkrisc wrote: post #132

Earlier quoted context omitted.

Step 1: Create economic conditions in which vast numbers of people can’t afford medical care Step 2: Offer them the “choice” of possibly receiving care by being medical guinea pigs for those who created the situation that deprived them of medical care in the first place. A coerced choice is a not a free choice.

A non-help, because waiting for the idealized version of help - is still less worth than a "could-help" but under coercing economic conditions. A feel-good ideological purity is less preferable outcome then a tainted Samaritan.

If it wasn't clear, my belief is that it would end up doing more harm than good, and that the status quo is the least-harm scenario between the two.

Re: Developing a cancer drug without Big Pharma: this hospital shows it can be done

#152

Post by yosame »

JPLeRouzic wrote: post #58
ramraj07 wrote: post #41

Earlier quoted context omitted.

Got my PhD from a lab that works on antibody drugs, they eventually even released one to the market. I’d argue that our current system is broken. There’s no reliable metric of drug effectiveness in any of our pre-clinical models, and thus we end up going into clinical trials quite blind indeed. And more often than not, what drug gets into trials has more to do with ego and politics than actual scientific merit. And t…

Many thanks for saying what I suspected when looking at the research publications and clinical trials on neurodegenerative diseases. I was starting to think I was an unproductive perpetual malcontent. For example, memantine has been tested 5 times in ALS. There even no pre-clinical studies that show any positive effect of memantine in animal models. This seems so bizarre to me.

Well to be fair, big pharma doesn't release preclinical results the same way that academia does. There might be no published work to support the hypothesis, but that doesn't mean they haven't done preclinical work.

Re: Developing a cancer drug without Big Pharma: this hospital shows it can be done

#153

Post by ramraj07 »

pfdietz wrote: post #61
ramraj07 wrote: post #41

Earlier quoted context omitted.

Got my PhD from a lab that works on antibody drugs, they eventually even released one to the market. I’d argue that our current system is broken. There’s no reliable metric of drug effectiveness in any of our pre-clinical models, and thus we end up going into clinical trials quite blind indeed. And more often than not, what drug gets into trials has more to do with ego and politics than actual scientific merit. And t…

The current system is like Churchill's description of democracy: the worst system, except for all the others. Biology is extremely complex. There's no substitute for actually trying things out on subjects in vivo. For many diseases we don't even know the cause (Alzheimer's for example). Drug companies have all the incentive in the world to improve the system to get better odds; it's not like they want drug discovery…

It’s ironic that you brought Alzheimer’s as an example since it exactly proves your point - drug companies pushed a therapy that targets a highly questionable _symptom_ of the disease, even though every single step of the process gave negative or inconclusive results. It was all about ego and desperate attempts to make profits using iffy drug candidates.

And “biology is complex” is the type of truism I hinted at. You can always say that whenever you fail. Biology is complex and Alzheimer’s is the most complex of them all, to be sure, but I hope you’re aware of the. Alzheimer’s cabal allegations that the entire field was mutilated by a bunch of people into believing and pursuing the wrong hypotheses for decades.

Re: Developing a cancer drug without Big Pharma: this hospital shows it can be done

#154

Post by ramraj07 »

mft_ wrote: post #92
ramraj07 wrote: post #41

Earlier quoted context omitted.

Got my PhD from a lab that works on antibody drugs, they eventually even released one to the market. I’d argue that our current system is broken. There’s no reliable metric of drug effectiveness in any of our pre-clinical models, and thus we end up going into clinical trials quite blind indeed. And more often than not, what drug gets into trials has more to do with ego and politics than actual scientific merit. And t…

It doesn’t (have to) cost billions to bring a (successful) drug to market. And if you pick a single successful example that was discovered in academia, was spun out into a small focussed biotech, and was in a disease area that didn’t require large or multiple studies to make it to market, you’ll have your anecdote to prove your point. Except… you’d be ignoring the costs of the 90% of drugs that fail in phase 1. You’d…

I am perfectly aware that this is the reason they blame for the insane costs - “we have to test so many drugs!”

Yet you seem to have assumed I’m oblivious to the reality when I’ve already pressed I’ve been in the deep end and am aware.

I’ve already given an explanation on why I don’t agree with “its still serendipitous and random” - the people working on it are not smart enough and are more interested in stoking egos and careers than doing real science, even if they’re capable of doing so.

“90% of the drugs fail in phase I” - why are you telling me that when I’ve already given an explanation on why that is so - we don’t have good preclinical models that correlate with drug effectiveness - is it that you didn’t understand what I wrote, or are also neck deep in this cultural quagmire you refuse to acknowledge it?

Re: Developing a cancer drug without Big Pharma: this hospital shows it can be done

#155

Post by mpnagle »

ALittleLight wrote: post #142
mpnagle wrote: post #136

Earlier quoted context omitted.

Hi hi. You may be interested in the VITALITY study out of China from 2022. 400+ people given FOLFOX + Avastin (standard of care, first line for colorectal cancer) vs FOLFOX + Avastin + high dose Vit C. https://pubmed.ncbi.nlm.nih.gov/35929990/ Roughly showed no change for the overall population, but a significant increase in progression free survival for folks with RAS mutations. As someone with a stage 4 colorectal…

Hey. Sorry about your diagnosis. Thanks for sharing. This is an interesting, though somewhat disappointing, paper. One thing I didn't get while reading it was the specific blood concentration achieved. I noticed they mentioned 12 rounds with 3 infusion days and 1.5g/kg. I'm assuming they injected that amount daily. I noticed they injected over a period of 3 hours. To my knowledge the half life of vitamin c in blood i…

I'd love to be in touch. I don't see your email in your profile. I'm mpnagle at gmail dot com. Thank you!

Re: Developing a cancer drug without Big Pharma: this hospital shows it can be done

#156

Post by mft_ »

ramraj07 wrote: post #154
mft_ wrote: post #92

Earlier quoted context omitted.

It doesn’t (have to) cost billions to bring a (successful) drug to market. And if you pick a single successful example that was discovered in academia, was spun out into a small focussed biotech, and was in a disease area that didn’t require large or multiple studies to make it to market, you’ll have your anecdote to prove your point. Except… you’d be ignoring the costs of the 90% of drugs that fail in phase 1. You’d…

I am perfectly aware that this is the reason they blame for the insane costs - “we have to test so many drugs!” Yet you seem to have assumed I’m oblivious to the reality when I’ve already pressed I’ve been in the deep end and am aware. I’ve already given an explanation on why I don’t agree with “its still serendipitous and random” - the people working on it are not smart enough and are more interested in stoking egos…

No need for anger - I think we're mostly in (violent) agreement here. :)

Maybe the one area we would significantly disagree is that I don't think it's simply that "the people working on it are not smart enough and are more interested in stoking egos and careers than doing real science".

Honestly, I've had discussions with so many mid-level smart trusted colleagues who always think that the higher-ups are making stupid decisions, and they'd do better. They're right that some of the decisions might be stupid (and you're probably right about "stoking egos and careers") some of the time, but people are promoted, decision-makers come and go, and the decisions (and failure rates) don't really improve. I (think I) see it for what it is, and agree that we lack meaningfully informative pre-clinical models, but I'm also comfortable to acknowledge the weaknesses of the system and be honest that I don't have all of the answers. At the moment, it's a heinously inefficient crap-shoot, but it's the best we've so far come up with.

But, prove me wrong. There are likely countless molecules that have been discarded that have therapeutic benefit waiting to be realised. (I don't mean to sound facetious here but) If you can do better, and are smarter than and will make better decisions than everyone else in the industry, you'll be a billionaire in short order, as this is literally the golden ticket in this industry that everyone else is missing.

Re: Developing a cancer drug without Big Pharma: this hospital shows it can be done

#157

Post by mft_ »

JPLeRouzic wrote: post #144
mft_ wrote: post #92

Earlier quoted context omitted.

It doesn’t (have to) cost billions to bring a (successful) drug to market. And if you pick a single successful example that was discovered in academia, was spun out into a small focussed biotech, and was in a disease area that didn’t require large or multiple studies to make it to market, you’ll have your anecdote to prove your point. Except… you’d be ignoring the costs of the 90% of drugs that fail in phase 1. You’d…

> It doesn’t (have to) cost billions to bring a (successful) drug to market > you’d be ignoring the costs of the 90% of drugs that fail in phase 1 It depends on what you call " bringing a drug to market ". _________________ * Phase I costs little, around $1M during the trial, and involves only a small group of participants (one or two dozen people), so it's not multi-center and it is manageable by a few people at a b…

I'm sorry, but for industry-sponsored trials your figures are off by up to an order of magnitude, despite the numbers in the (18 year old) reference.

Phase I: a small biotech I know of in oncology has phase I costs in the order of $500,000 per patient; this is a higher-end cost, due to their sites being in the US (more expensive than Europe) and because as a small biotech they're had to outsource virtually every aspect of running the trial. In big pharma, per-patient costs were more like $70-100k per patient, but this was just the pure money paid patient (to the site, and external costs like drug supply and shipping) and ignored the cost of laboratory, clinical, operations, and data management work that was being done in house. All told, it would typically be hard to get even a phase I study completed for less than 10x your estimate, and this is before you consider any additional recruitment needed between dose escalation and phase III.

Phase III: again it depends on many factors, but in big pharma a trial cost of $100-200k per patient was again not unreasonable, and typical phase III trials where you're comparing to a meaningful established medicine are larger than 100-200 patients. A biotech I know of is unable to run a phase III for a promising drug without finding a partner to support the majority of the cost (which is >100m EUR in oncology) and they're not wasting money.

---

A less anecdotal approach is to consider the total R&D costs of companies across a given timescale, and divide by the number of successes. It's a pretty old reference too, but Matthew Herper did this in 2013. [0] Yes, there were some outliers with low costs, but you'd have to understand the details for context. The typical costs were in the hunderes of millions to billions per successful drug.

[0] https://www.forbes.com/sites/matthewherper/2013/08/11/the-co...

Re: Developing a cancer drug without Big Pharma: this hospital shows it can be done

#158

Post by ramraj07 »

mft_ wrote: post #156
ramraj07 wrote: post #154

Earlier quoted context omitted.

I am perfectly aware that this is the reason they blame for the insane costs - “we have to test so many drugs!” Yet you seem to have assumed I’m oblivious to the reality when I’ve already pressed I’ve been in the deep end and am aware. I’ve already given an explanation on why I don’t agree with “its still serendipitous and random” - the people working on it are not smart enough and are more interested in stoking egos…

No need for anger - I think we're mostly in (violent) agreement here. :) Maybe the one area we would significantly disagree is that I don't think it's simply that "the people working on it are not smart enough and are more interested in stoking egos and careers than doing real science" . Honestly, I've had discussions with so many mid-level smart trusted colleagues who always think that the higher-ups are making stup…

I would love to prove my point by actually becoming a billionaire, but my point is that the system is stacked against folks like me. Gotta have a nature paper to get a job in Genentech fresh out of PhD. Who gets nature papers? People who join labs that already publish nature papers. Who gets to join there? Valedictorian Who undergrad in top schools. Apparently the odds are stacked the moment you slack off in eigth grade lol.

I have done my PhD, I need to take a break to actually take care of my family and immigration. I hope to get back to this field at some point, in my own terms, and see if I can succeed. If it works, it works! If not Who cares right! Let's see.

Re: Developing a cancer drug without Big Pharma: this hospital shows it can be done

#159

Post by pattymanners »

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