https://web.archive.org/web/20240909093450/https://www.statn...
The key reason Pfizer passed was that executives didn't think patients would accept a new therapy that required injection to administer:
Despite our emerging results, the Pfizer executives in charge of research and external alliances told us the company did not want to develop a new diabetes therapy that required injection, a space held exclusively by insulin since 1922. They gave us a year to find a way to deliver GLP-1 via transnasal, transcutaneous, or oral administration. Effective delivery by any of these approaches would have been great, but we knew success was unlikely in the year they gave us. Our effort was predictably unsuccessful, and after four years, Pfizer terminated our agreement as permitted under the alliance contract.
The first commercial GLP-1 receptor agonist, Exenatide, went to market as an injectable medication in 2005 [1]. Orally delivered GLP-1 medications didn't come to market until 2019 when orally dosed semaglutide was approved as Rybelsus [2].
Now that injected GLP-1 drugs are among the most-prescribed drugs in America, I wonder if drug company executives are going to be more receptive to drug candidates that require injections. There are a lot of molecules (especially peptides) that are degraded by the digestive system; maybe people will be more willing to inject medications when so many have started self-injecting for GLP-1 drugs or know someone who has.
In large organizations, I guess a big chunk of success comes from being able to navigate all these political ups and downs.
Source: I took compounded Mounjaro and compounded Ozempic/semaglutide.
Pfizer's strengths are regulatory compliance, M&A and global manufacturing. They suck at research and clinical development. Losing the GLP-1 race was predictable as they simply don't prioritize emerging science compared to other mid-sized and large pharmas.
This tells me that research on the drug is old and that increases security on its use.
There are many drugs that have been developed since then, and each approval seems to have slightly better drug properties.
The age of research on a drug is not very indicative of safety, either. Rather, broad study and time are far better. I'd take five years of clinical trials on hundreds of thousands of people over 5000 years old research on hundreds of people.
An injection to cure obesity is a small price to ask, as any person that has been obese will tell you. They could have determined this from a simple survey.
What was the human cost of their decision? Maybe an entire delayed decade of progress? How many people died, that could have been saved?
I would love to meet some of these executives and understand what they were thinking, and if they understand/regret the impact of their foolishness.
Insulin is injectable so GLP-1 was thought to be at best marginal improvement over already existing protocol - so likely profitable product but not excessively so. Company has limited resources so decisions on cuts have to be made and some of those decisions are naturally wrong - drugs are unpredictable.
On regret - they missed on 30B+ of profits so of cause they regret it.
You're missing the primary point: GLP-1 was investigated as another me-too diabetes drug, for which there were many injectable drugs available.
It wasn't until much much later that it was discovered to be an obesity drug. It was a completely coincidental and accidental discovery.
It turns out that most science is like that. We make the most important discoveries unexpectedly and by chance. Which is why you should always distrust the politicians that mock and ridicule science for sounding ordinary or obvious. That's where the real magic happens.
Define "much much later"
It was known by the early 1990s that GLP-1 slowed stomach emptying, with a key study in 1993 demonstrating its effects on gastrointestinal functions like gastric emptying, leading to longer feelings of fullness, which is the central mechanism at work here. See, e.g., https://pubmed.ncbi.nlm.nih.gov/35635627/
It just took eons for someone to decide that therefore maybe it was worth thinking about for weight loss.
That part is due to lack of exec vision - the fact that weight loss was not commonly treated with drugs (amphetamines work, but ...) meant they never thought really that hard about it.
To be fair, that lackof vision is not unreasonable in the sense that they have both plenty of high value targets, and plenty of arrows to shoot at them. Most of the arrows miss of course, but that's okay.
There is not always tremendous incentive to try new targets until they start missing the target too much, or the value of existing targets drops.
They almost certainly give up on, or ignore/drop/whatever, a near infinite number of things that may have turned into life saving drugs, billion dollar blockbusters, you name it.
At least right now, that's how this kind of thing works, for better or worse.
However, this is quite separate from when x was discovered to be a y, as it is here.
FWIW - I'll offer another lack of vision in the same vein - by slowing stomach emptying significantly, GLP-1 also causes the same amount of alcohol to do significantly less damage, because it enters your small intestine in much smaller amounts and over a much longer period of time. So much so that is a very effective treatment for alcoholism because it both reduces alcohol craving, and causes significant amounts of alcohol to do less damage. See, e.g., newly published studies like https://pubmed.ncbi.nlm.nih.gov/37192005/ and https://jamanetwork.com/journals/jamapsychiatry/fullarticle/...
Again, this should have been somewhat obvious to study a long time ago, but it wasn't started until 2 years ago.
It also turns out to reduce drug cravings, which is more unexpected, but would have been discovered much earlier with better vision.
Well, COVID certainly put an end to those fears (by consumers). Coincidentally, obesity was also said to increase COVID risk. Hollywood couldn’t have scripted it - no pun intended - any better.
Injections are no longer a only-if-absolutely-necessary. The stigma is mitigated.
