[adamontherun]

Acquired had a great episode earlier this year that really connects with this. They talked about how Novo Nordisk stuck with GLP-1 research for decades, even when it didn’t seem like a sure thing.

A big part of that was Mads Krogsgaard Thomsen, who pushed for GLP-1 research at Novo even when he faced a lot of skepticism and wasn't always treated well for it. Compare that with MetaBio—mentioned in the study—where Pfizer pulled the plug early and missed the boat entirely. Novo’s persistence, especially Thomsen's, led to Ozempic and Wegovy

[unavoidable]

So much of this is hindsight bias though. There were no shortage of people with ideas and companies pursuing obesity drugs through a number of different pathways. Only in hindsight does it seem "genius" that Thomsen persisted and succeeded where nobody else did. But there are dozens, hundreds, of other smart people who were pursuing other pathways who did just as much stubborn work but didn't get a result. That's just pharmaceuticals.

Take, for example, another high profile disease - Alzheimer's. First there was the beta amyloid theory, then there was the p. gingivalis theory (this one was talked about so highly on this very forum, but ended in an equally high profile failure* of a pivotal clinical trial by Cortexyme). Now there are viral and metabolic theories. Each of these theories have a few dozen companies and armies of PhDs stubbornly pursuing a miracle drug, but so far it remains elusive.

* We also like to talk about "failures" of clinical trials, which is technically correct language, but evokes in the public imagination the wrong idea. A clinical trial failure doesn't mean there was something wrong with the idea or process (long before it ever gets there, a drug candidate would have been proven to be very effective in lab tests and animals). It's just that 90% of clinical trials don't end up working due to complex disease pathways and numerous unknown factors. It would help if we talked about "negative proofs" (i.e. proving something doesn't work is also valid), but it's not quite as catchy.

[ZoomerCretin]

> First there was the beta amyloid theory

First? Isn't the beta-amyloid cabal still blocking all Alzheimer's research unless the researchers find a way to even tangentially support that long disproven theory?

[refurb]

> So much of this is hindsight bias though. There were no shortage of people with ideas and companies pursuing obesity drugs through a number of different pathways. Only in hindsight does it seem "genius" that Thomsen persisted and succeeded where nobody else did. But there are dozens, hundreds, of other smart people who were pursuing other pathways who did just as much stubborn work but didn't get a result. That's just pharmaceuticals.

Exactly.

There are plenty of examples where the opposite choice was made - argue for continued development despite high uncertainty.

The CETP inhibitors is a good one. Pfizer flushed several billion dollars down the drain with the decision to push it through phase 3.

[condiment]

https://pubs.acs.org/doi/pdf/10.1021/acsptsci.9b00048

^^ Here's an article written by Lotte Knudsen, referenced in the original post, that further tells the story of how GLP-1 was first developed into a drug (as liraglutide) and approved for human use. There were a lot of false starts and additional practical problems that needed to be solved in order to yield a viable medication.

After reading the OP I was surprised to learn that Novo Nordisk picked up the research only a couple of years after GLP-1 was abandoned by Pfizer, after which it took 5 years to develop the initial medication and another 12 years to make it through FDA approval. Even after all that, the primary indication was for diabetes. It took another 7 years for semaglutide to make it through approvals and bring GLP-1 into the public consciousness.

When you consider the amount of time involved, and the sustained investment required, it's difficult to fault the execs at Pfizer for their decision to shut the project down. Obesity wasn't nearly as prevalent then as it is now, and it seems likely they had funded the startup specifically because of the author's prior research into nasally-administered meds. It's even possible that the shutdown decision had little to do with the primary area of research.