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 the folks involved in these types of activities are (IMO) the most unoriginal types I’ve ever seen.

There’s a lot we can do to improve our drug development process. It really doesn’t need to cost billions to bring a drug to the market. But the odds are stacked against anyone with a contrarian hypothesis and I just figured I’d save my sweat and leave this field instead.

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 be ignoring the huge amount spent on discovery across the industry that never leads to a successful candidate.

Drug discovery and development is difficult because, for all of our clever science, it’s still essentially serendipitous and random. And we’ve not yet figured out how to make a production line out of something that’s random, try as we might. And it’s expensive because of the failures as well as the cost associated with success.

I'd agree with a lot of that in terms of both many drugs being 'discovered' in clinical trials as oppose to earlier ( a lot of it it about choosing the right patients and dose ), and the differences in mindsets between researchers and those often involved in the clinical trial side.

One of the things you've missed is the strong restrictions put on pharma in terms of promoting use of existing drugs beyond the existing approval ( which makes sense ), and the almost complete freedom Doctors have to do what they want - they can just decide to prescribe something off-label if they think it might help.

It can take a very long time for new ideas to become new products - and a lot of that is inertia ( nobody else is doing it ).

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.

Some drugs not being able to make it into phase 1 clinical trials sounds like a functioning regulatory system to me. The bar isn't astronomically high for a phase 1. Like sure, you can't just do it in your garage like a web startup, but there are reasons for that. If anything, there are way too many drugs floating around in LDT right now, hence why those are being faded out.

Is this a market that can be disrupted? It sounds if you know how to save a few billion and introduce more science based drugs, it’s ripe for an overtake.

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 to be such a crapshoot.