Pfizer's stocks take another hit after halting clinical trials for their weight-loss medications.

And why finding a miracle weight-loss drug is more complex than we make it out to be.

In another hit to Pfizer and its investors the pharmaceutical giant saw a 5% decline to their stocks on December 1st.

Be careful of misinterpreting this graph. Note that the y-axis is relative to the highest/lowest points. The overall dip seems to be around 2 dollars, or around 5% of Pfizer’s prior stock value. Image from yahoo! Finance

This came after Pfizer reported that they would no longer progress their own GLP-1 RAs to further clinical trials after noticing high patient dropout and a concerning number of side effects such as nausea and vomiting. In this case, one potential drug named Danuglipron has been halted and seeing possible reformulations coming down the line in the near future. This comes months after Pfizer halted clinical trials for another potential GLP-1 RA Lotiglipron due to concerningly elevated levels of liver enzymes within blood of patients from the treatment group, suggesting possible hepatotoxicity related to this drug.

Pfizer includes the following within their press release published yesterday regarding their discontinuation of Danuglipron:

While the most common adverse events were mild and gastrointestinal in nature consistent with the mechanism, high rates were observed (up to 73% nausea; up to 47% vomiting; up to 25% diarrhea). High discontinuation rates, greater than 50%, were seen across all doses compared to approximately 40% with placebo. No new safety signals were reported and treatment with danuglipron was not associated with increased incidence of liver enzyme elevation compared to placebo. Data from this study will be presented at a future scientific conference or published in a peer-reviewed journal.

I have covered this new generation of medications previously as it appears that this is the direction that pharma companies are taking. Unlike the current iterations of GLP-1 RAs on the market these new medications are expected to be easier to administer and cheaper to produce, making them highly sought out by companies attempting to pivot towards a new market as COVID vaccines and treatment interest continue to decline.

Please take a look at the prior article and note the differences in structure between GLP-1 RAs already on the market and ones that make up this new generation:

It appears that Pfizer may have hoped to enter into this burgeoning market topped by other companies such as Novo Nordisk, which is now considered the largest company in Europe’s stock markets due to the success of their GLP-1 RAs Ozempic and Wegovy:

As of now Pfizer doesn’t appear as if they will halt their attempts at releasing their own GLP-1 RAs, with talks suggesting that Pfizer may be attempting to alter the release rate of Donuglipron, with the hope that a a slower release may attenuate some of the side effects:

“We believe an improved once-daily formulation of danuglipron could play an important role in the obesity treatment paradigm, and we will focus our efforts on gathering the data to understand its potential profile,” said Mikael Dolsten, MD., PhD., Chief Scientific Officer & President, Pfizer Research and Development. “Results from ongoing and future studies of the once-daily danuglipron modified release formulation will inform a potential path forward with an aim to improve the tolerability profile and optimize both study design and execution.”

But as more and more people take interest into these alleged weight-loss drugs we are seeing additional side effects that were not normally reported (or at least overlooked) such as stomach and intestinal paralysis, with possible suicidal ideation being the newest possible side effect being investigated:

Given these increasing concerns over safety it begs the question if these newer generations of medications will be safer.

As I remarked in my prior post these drugs are attempting to mimic the agonistic effects of a hormone that induces widespread effects throughout the body. This includes inducing insulin secretion from the pancreas, signaling the stomach and intestines to slow down digestion, and can bind to various neurons within the CNS to possibly induce a feeling of fullness- the latter mechanism now being looked at as a possible explanation for GLP-1 and these drugs appearing to reduce the need for addictive substances.

All this to say that the effects of these drugs are not one-to-one. They are not only reducing weight or feelings of hunger. Rather, they are likely inducing widespread effects throughout the body. This tells us that there’s a lot more that’s going on, and certainly a lot more than is being reported by these companies. Again, these drugs are intended to mimic the effects of an endogenous hormone.

And this may be the likely reason why we aren’t close to having a miracle weight-loss drug, and in reality may be the reason why we should be careful of wishing for such a medication if it were to ever appear. The body is far more complex than we make it out to be, and when science takes a reductive approach that focuses only on dealing with symptoms or a specific problem we may lose sight of the forest for the trees.

The growing evidence suggests that there’s a lot more going on with GLP-1, and so we should expect the same for these medications which have far longer half-lives and may be more bioactive.

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