[inglor_cz]

"Why would anyone make a drug if the current prevalent treatment was as good as a functional cure?"

I am not sure whether you ask for economic why, or an overall why.

The overall why seems easier to explain:

a. The new drug may be cheaper.

b. The new drug may be safer. (e.g. no risk of anaphylaxis etc.)

c. The new drug may not need cold storage (huge problem outside the First World).

d. The new drug may have other properties that the original does not have (e.g. being taken once a day instead of four times a day, not requiring people to stay off specific food etc.)

e. The side effects (such as vomiting) may be lower.

In general, it is always better to have alternatives in medicine.

[bonsai_spool]

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.

[s1artibartfast]

I dont know why you are being rude about a topic you know nothing about. As some who actually does this for a career, they are largely correct. Dose frequency and side effects especially are major reasons. I would add route of administration and patient convenience as well.

Anti-vegf treatments for blindness are a good example if you want to research. They all have basicly the same effect in terms of letters preserved on an eye chart if dosed as perscribled.

It's a 15 billion dollar per year Market that resolves on the basis of the longest dose interval and side effects.

You can look at the bevicizumab, to ranibizumab, to aflibercept, to brolucizumab, to faricimab drug programs. There are also dozens of failed programs in this area and perpetually new drugs and Gene Therapies looking to break into the market.

Perhaps an even more salient example would be pill based GLPs looking exploit the listed factors

[vibrio]

To add a somewhat cynical view, a significant part of the original motivation for the ranibizumab (Lucentis) development was due to pricing arbitrage across diseases. bevicizumab was priced based on uses in cancer indications with a “large” volume (many mls) used for systemic infusion. The same product injected into the eye, in say a 1:1000 volume, could be efficacious for AMD, but pricing per volume would be trivial amount at the bevi cost per volume. So they tweaked the active ingredient to a new product (exact same mechanism ) and raised the price per volume to a market standard cost per treatment. There may be some pk-type benefits to the derivative , but the pricing context is an industry case study.

[s1artibartfast]

Yeah, I think that's especially relevant here too and reinforces the phenomenon where US hcps will opt for the best independent of price, even if the marginal benefit is vanishingly small or hypothetical/not data driven.

Some providers did opt to self-compound avastin for off label use mostly in Europe but also in the US.

The idea that Pharma companies would pass on developing a product 1% better than keytruda, or that hcps would pass on buying is laughable

[bonsai_spool]

Not being rude, and I definitely know about medicine.

I explained in sibling that I understood the Lowe article to be about new research (as a researcher, I don't often think about how hard it is to make a GLP survive the stomach but I do think about how incretin biology works). I guess these VEGF agents you list feel like a very straightforward engineering question (can we make an antibody that targets VEGF, humanize its Fc etc) while Lowe brings up conceptual areas like PCSK9, HMG-CoA reductase.

I still maintain that the 1% better thing is not going to lead to incredible success because rational actors aren't going to change their prescribing patterns each time a new agent gets approved.

[s1artibartfast]

I dont think you have an accurate model of how US prescribers and patients operate.

They want the best, and are willing to sepnd 10x the price or switch treatment to secure that 1% survival, extra week of dosing interval, or the ability to inject at home via mail instead of some sweaty infusion clinic.

I used to think like you before transitioning from medical devices to pharmaceutical development.

The USA is the only real Market that matters for drug development. Unlike the with marginal benefit pricing and National negotiation, the US market is consumer Centric, with patients and their providers wanting the best, even if it is marginal. That 1% means that you can either take the market share or 10x the price.

> I guess these VEGF agents you list feel like a very straightforward engineering question

Each of those straightforward engineering questions takes about 100,000 labor-years and a billion dollars to get approval.

[s1artibartfast]

Oh fun trivia about those straightforward engineering problems was Novartis beavu. It had a few percent higher Side Effects than standard of care after lunch. This was enough to cause Novartis (a top 5 or 10 Pharma company) to essentially cease all ocular drug research and sell off much of their ocular portfolio.

[refurb]

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.

[bonsai_spool]

You are correct. I disagree with alternatives being better as a rule but these are clearly areas where there's a market (to wit, people don't like injecting themselves and prefer pills).

[jleyank]

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

[jleyank]

You could compare ibuprofen and naproxen. One lasts 4-ish hours while the other, having different functionality, lasts 12-ish hours.

[nradov]

What an ignorant comment. Are you not familiar with Mavyret, Vosevi, or Xatmep?

[bonsai_spool]

I did ask for examples. These aren't really the sort of thing the article is talking about - they're just recombinations of existing medications. I admitted in another comment that I wasn't thinking about these but instead launching a new program to find a new mechanism (which I still haven't found an example of).

[inglor_cz]

IIRC there are serious attempts at "vaccination plasters", which would solve the cold storage problems of classical vaccines. Some really bad infections survive in reservoirs far from the closest hospital with reliable electricity.

And frankly your comment about "facile thinking" is totally unwelcome. Have you seen someone vomiting their guts out after chemo? That is torture.

Oncology is one field where every less punishing treatment would be useful. Some patients have to be taken off otherwise life-saving treatments because they cannot tolerate them. That is true even with well-treatable cancers such as Hodgkins, which 90+ per cent of patients survive.

[bonsai_spool]

I have seen these people, but we are speaking about drug companies making new drugs. I am not aware of an example of a new chemotherapeutic developed to reduce the side effects of a previous agent - that seems even less reasonable from an ROI perspective since we have good agents to control chemo-associated nausea. (edit) If a new agent happens to cause fewer side effects, that is welcome. But how would you justify the risk of the new agent not working at all?

The search for different formulations of an active agent seems a little unrelated (sibling comment to yours) but I concede that I didn't exclude that in my earlier argument.

--

My point is that several posters here are giving arguments from first principles ('yes of course we would want to keep trying to make more medications because more options is better than fewer options') but not engaging with the enormous cost such a rationale would entail.