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.
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
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
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.
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.
And the notorious inhaled insulin that Pfizer launch (and horribly failed).
There are many ways to differentiate drugs, not just efficacy.
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.
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.
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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.