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Posted10 days ago
Key Takeaways
https://web.archive.org/web/20240909093450/https://www.statn...
The key reason Pfizer passed was that executives didn't think patients would take up 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 destroyed 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.
Source: I took compounded Mounjaro and compounded Ozempic/semaglutide.
Just one little clap sound, you feel a little pat on your arm, and the sensor's already made it where it needed to with no pain.
When you remove the sensor it's a little bit of a shock when you see the sensor wire and realize just how small it was and how you never felt it run around inside your arm for a couple weeks.
and, for me, its always been the needle moving around thats been mentally disturbing. digging around vecause they missed for the blood draw, trying to hold a large vaccination dose steady as it needs to be injected over 20seconds. So, I suspect the speed itself reduces discomfort.
But in either case, the answer for subcutaneous injections using needles sized 29g and smaller is no.
I don't know the pharmacokinetics of GLP-1 drugs but my guess is that they don't have the same sort of effects on SC tissue?
Before I had a CGM I did somewhere around 20,000 blood glucose tests over the course of a decade using about 1 cm^2 of forearm and the skin there is clearly not in great shape -- but it's worsened on the level of "looks like the skin of someone who is a decade older or spent too long in the sun" rather than anything medically problematic.
They do, but nothing like insulin does. GLP-1 drugs are more centrally and viscerally active than subcutaneously active, so the effects locally are more related to the physics of injecting solutions subcutaneously than the drugs themselves. They're also much smaller doses than are needed for insulin in general, so the volume averaged over a week is pretty tiny.
Also, as a result of the relative lack of local activity, injection sites are basically unlimited (anywhere from above the knee to above the elbow, except the neck) without fear of lipohypertrophy in the local area.
I really don’t understand this phobia of needles at all. After two days with one system or the other, you get used to it—there’s no pain, it’s just a mental issue of “having to make the gesture.”
My friends used to laugh at how normal it was for me to inject insulin outside a restaurant, while walking, chatting, and smoking at the same time.
Heroin addicts and presumably anyone else who frequently injects into a vein can cause damage to the veins.
In large organizations, a lot of success comes from being able to navigate all these political ups and downs.
https://www.sciencenews.org/article/vaccine-beer-polyomaviru...
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.
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 meant they never thought about.
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.
Every major discovery in biology looks like GLP-1: apparently locking in finding a new class of targets and or therapies. It's very easy to string together promising theories from sets of papers, but far harder to establish them with hard data tha comes at the cost of actual humans using the potential drug in trials.
I'm told that one of the very few parts of the stock market where subject matter experts can generate alpha is in biotech, by following the data of small biotech closely. However the fortunes of individuals and the market as a whole is largely downstream of larger macroeconomic forces, such as Fed interest rate changes, that determine the level of investment in new high risk economic activity versus keeping money in bonds.
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.
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.
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