Washington Post: Pfizer May Have Sat on an Alzheimer's Treatment

[kevwun 16305]

In 2015 researchers at Pfizer discovered that Enbrel, an arthritis med of theirs, might be effective at preventing and treating Alzheimer's.  They wanted to do an 80 million dollar clinical trial.  Mgmt and Pfizer decided not to and also chose to sit on the information and not publish it.  In a completely unrelated note, the patent for Enbrel expired in 2018, which means using Enbrel as an Alzheimer's medicantion wouldn't have been profitable for the company.  Pfizer insists the decision was purely for scientific reasons.

 

https://www.dispatch.com/zz/news/20190604/pfizer-had-clues-its-blockbuster-drug-could-prevent-alzheimers-but-kept-it-secret

[drt 645]

If true, fuck them. That’s a terrible disease. 

[Anastasis 23703]

An effective treatment for AD is the holy grail of neuroscience development at the moment. Pfizer and many many other companies have spent billions trying to bring novel AD drugs to market. All of the recent develop programs have failed (I think they are going after the wrong targets). In this case, Pfizer had weak signals from exploratory observational studies based on administrative claims data. By their rationale, the biological plausibility for a true effect was unlikely since etanercept doesn't cross the blood brain barrier. Given the study design and the limitations of claims in particular to identify AD, dementias, and other forms of cognitive impairment as endpoints, and given the history of failures in this therapeutic area, I don't find fault in taking a skeptical posture wrt these data when considering a development program that can run into the hundreds of millions of dollars. An extremely high risk proposition all things considered. In this case, the only fault that I find is that Pfizer should have published the findings of their analysis for consumption by the scientific community. If after a careful examination of the findings others want to use chase after a TNF treatment for AD, they should be free to do so.     

Edited June 5, 2019 by Anastasis

[TwiceHorn 31995]

It would appear that the expiration of the patent for Enbrel for autoimmune disorders is irrelevant, as Pfizer probably could have obtained another one for the new use.

Also not sure what commercial motive they might have for not publishing the studies.

[Pato del Muerto 53344]

8 minutes ago, TwiceHorn said:

It would appear that the expiration of the patent for Enbrel for autoimmune disorders is irrelevant, as Pfizer probably could have obtained another one for the new use.

Also not sure what commercial motive they might have for not publishing the studies.

This is what I was thinking. New use means new patent means more money. Drug was already developed and approved by fda, so the costs would be much less to perform trials for new use efficacy. 

[Hornin04 262]

While I think drug companies are crooked as hell, I agree that there was not likely a financial reason behind this (other than the finances of wasting money on a clinical trial that wouldn't yield good results). They could have filed a patent for it and made money. Actually I bet they did file a patent in case it did.

 

One case example is Allergan and their glaucoma drop Lumigan. A side effect of longer eye lash growth was discovered and they rebranded the same med as Latisse and sell it as a beauty product to enhance eye lashes. Both are still brand name prescriptions and making money.

 

 

[Anastasis 23703]

Exactly. Pharma excels at repacking their initial R&D investment to extend their revenue generation. Given demographic trends, a novel AD treatment would be a fucking blockbuster. WaPo really did this particular issue a major disservice in my opinion. Just garbage. The reality is that PFE has burned billions of dollars in the process of trying to develop novel AD treatments based on a treatment paradigm that appears to be a dead end. But I guess we are supposed to be mad at them for not burning 100MM more.    

[4HE 156]

9 hours ago, Horny04 said:

While I think drug companies are crooked as hell, I agree that there was not likely a financial reason behind this (other than the finances of wasting money on a clinical trial that wouldn't yield good results). They could have filed a patent for it and made money. Actually I bet they did file a patent in case it did.

 

One case example is Allergan and their glaucoma drop Lumigan. A side effect of longer eye lash growth was discovered and they rebranded the same med as Latisse and sell it as a beauty product to enhance eye lashes. Both are still brand name prescriptions and making money.

 

 

Latisse is no longer brand only. Minor detail that doesn’t change the gist of your post.  Just trying to keep it factual. 

[Reagan1k 3042]

19 hours ago, Anastasis said:

Exactly. Pharma excels at repacking their initial R&D investment to extend their revenue generation. Given demographic trends, a novel AD treatment would be a fucking blockbuster. WaPo really did this particular issue a major disservice in my opinion. Just garbage. The reality is that PFE has burned billions of dollars in the process of trying to develop novel AD treatments based on a treatment paradigm that appears to be a dead end. But I guess we are supposed to be mad at them for not burning 100MM more.    

Thanks for this take.  When I read the article it appeared to be a bunch of anecdotal "stuff" cobbled together looking for a bad guy on whom to pin a target.

[TwiceHorn 31995]

21 hours ago, Pato del Muerto said:

This is what I was thinking. New use means new patent means more money. Drug was already developed and approved by fda, so the costs would be much less to perform trials for new use efficacy. 

I don't know, have to ask anastasis, but I don't believe "new use" approvals are significantly cheaper than the original use approval.  You'd think at least safety would be established, but given that there's probably a different dosing regimen (there might need to be to obtain a patent), there's probably a different safety profile to consider, as well.

Also, by burying it, they make it more likely that someone else gets a patent on the new use.  By quietly publishing, they could sink any attempt by another to patent it.

I'm not finding a whole bunch of insidiousness here.

Pharma marketing practices are the problem more than any single thing.  They wield too much influence with the medical community and use deceptive tactics to keep profitable (but not particularly efficacious) drugs at the "top of the list" and unprofitable ones at the bottom.  The FDA processes have some dire unintended consequences, too.  The rest of it is just noise.

Edited June 6, 2019 by TwiceHorn

[kevwun 16305]

I knew some folks here would have good insight.  Seems like this biggest issue is Pfizer sitting on the info.  There appears to be no legit reason for that.  Not pursuing it is defensible, failing to publish on the off chance it could lead to a cure or prevention is not.

Edited June 6, 2019 by kevwun

[Anastasis 23703]

34 minutes ago, TwiceHorn said:

I don't know, have to ask anastasis, but I don't believe "new use" approvals are significantly cheaper than the original use approval.  You'd think at least safety would be established, but given that there's probably a different dosing regimen (there might need to be to obtain a patent), there's probably a different safety profile to consider, as well.

It would seem to me that the investment to submit a supplemental NDA for a new indication should cost less. They can potentially recycle some of their clinical trial data. How much so?  Not sure. I would assume substantially cheaper in most cases, but probably highly variable. 

1 hour ago, TwiceHorn said:

Pharma marketing practices are the problem more than any single thing.  They wield too much influence with the medical community and use deceptive tactics to keep profitable (but not particularly efficacious) drugs at the "top of the list" and unprofitable ones at the bottom.  The FDA processes have some dire unintended consequences, too.  The rest of it is just noise.

Agree with this take.

1 hour ago, Reagan1k said:

When I read the article it appeared to be a bunch of anecdotal "stuff" cobbled together looking for a bad guy on whom to pin a target.

Reads like a hit piece, imo. Internal source was probably disgruntled Pfizer employee from the disbanded neuroscience group. 

1 hour ago, kevwun said:

Seems like this biggest issue is Pfizer sitting on the info.  There appears to be no legit reason for that.  Not pursuing it is defensible, failing to publish on the off chance it could lead to a cure or prevention is not.

I agree that the data should have been published.  I mean just throw it at an Alzheimer's focused conference as a poster presentation.  Unless there were some concerns regarding the execution of the analysis or the study design, I am surprised that their SOPs would not require some form of dissemination. If they didn't previously, they probably will now.  Or more likely, the company will implement stronger controls on exploratory analyses like this before they are conducted. If conducting exploratory hypothesis generating research with claims data is going to be used against Pharma when they don't chase every signal with a full blown, costly, large scale RCT, they are going to be very careful about what sorts of signals they might uncover and the types of questions they ask. Which is really counterproductive and stifling in my opinion. And why the WaPo piece is particularly damaging. 

BTW, here is a paper from 2016 with similar study design and findings to the internal Pfizer work: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585782/

And an pilot investigator initiated RCT from 2015 showing no effect on cognitive measures in patients with AD. Funded by, wait for it.....Pfizer: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451045/

[52-80 19374]

On 6/5/2019 at 11:40 PM, Anastasis said:

An effective treatment for AD is the holy grail of neuroscience development at the moment. Pfizer and many many other companies have spent billions trying to bring novel AD drugs to market. All of the recent develop programs have failed (I think they are going after the wrong targets). In this case, Pfizer had weak signals from exploratory observational studies based on administrative claims data. By their rationale, the biological plausibility for a true effect was unlikely since etanercept doesn't cross the blood brain barrier. Given the study design and the limitations of claims in particular to identify AD, dementias, and other forms of cognitive impairment as endpoints, and given the history of failures in this therapeutic area, I don't find fault in taking a skeptical posture wrt these data when considering a development program that can run into the hundreds of millions of dollars. An extremely high risk proposition all things considered. In this case, the only fault that I find is that Pfizer should have published the findings of their analysis for consumption by the scientific community. If after a careful examination of the findings others want to use chase after a TNF treatment for AD, they should be free to do so.     

are you premed?

[Anastasis 23703]

2 minutes ago, 52-80 said:

 are you premed?

No, but I am partial to the advice to start drinking heavily.