Pfizer 's anti-inflammatory drug questions (revised title)

[Fiver]

Pfizer had clues its blockbuster drug could prevent Alzheimer’s. Why didn’t it tell the world?

https://www.washingtonpost.com/business ... ae9c09c222

Anyone else seen this?

[mike]

Yes, depressing

[WhatNext]

Has anybody seen this?

https://www.washingtonpost.com/business ... 27ba0fb094

[Fiver]

Yes. But exciting that they saw a promising signal. This drug is a biologic, an antibody type protein that is a TNF-alpha inhibitor. Apparently, it usually does not enter the brain. So, this implies that reducing peripheral inflammation can be beneficial. There are other biologics, similar antibody proteins on the market to do similar things. They are all expensive ~$15,000 a year. Other, small molecules that have TNF-alpha inhibitory properties are curcumin (if you can get it into the body, which can be difficult) and buproprion (the anti-depressant). Buproprion seems interesting - it is inexpensive and generic, and seems to work to some degree at low levels.....though so far I can't find the data on doses needed for TNF-alpha inhibition in humans. They apparently also reevaluated some of the older NSAIDs research to search for hidden signals and there is some hint that regular ole' anti-inflammatories might help to some small degree, if used in midlife.

So, Pfizer wasn't going to follow up on this. But some one made sure the community knew about it anyway. And now we can explore the potential benefits.

Now sure why I am looking at it in a positive way this morning - must be some good coffee I'm drinking.

[Fiver]

Yes, there are two new threads about it - but not a lot of comments yet.

[BrianR]

Pfizer had clues its blockbuster drug could prevent Alzheimer’s. Why didn’t it tell the world? ...

FWIW, some Twitter commentary (responding to @EricTopol comment on WaPo article)

Atul Butte @atulbutte: Pfizer study results: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451045/

Don Lyall @Don_lyall: RA drug might make sense and certainly can affect the brain: https://www.nature.com/articles/s41591-018-0336-8 https://www.sciencedirect.com/science/a ... via%3Dihub

Colm Cunningham @Cunningham_Colm: TNF blocker may not need to enter brain. We found that elevated systemic TNF is associated with more rapid decline in AD https://www.ncbi.nlm.nih.gov/pubmed/19738171, additional studies show impact of systemic inflammation on neurodegeneration https://www.ncbi.nlm.nih.gov/pubmed/22674585

[TheresaB]

I didn't read the article, but Rheumatoid Arthritis is an autoimmune disease which causes inflammation in the body. Inflammation in the body is a risk factor for Alzheimer's. Inflammatory is Dr Bredesen's Type 1 Alzheimer's as discussed in his book, The End of Alzheimer's. Makes sense that a drug that helps reduce inflammation may reduce the risk of Alzheimer's, I just wonder what side effects the drug has.

[WhatNext]

Yes. But exciting that they saw a promising signal.

That's what I thought too. They're not going to study it because they won't be able to profit from it, but a reduction in risk of 64% was indicated based on "hundreds of thousands of insurance claims", which sounds like a study to me. The drug is an anti-inflammatory. and there's been a LOT of discussion of the need to reduce inflammation here, which both adds credence to and is confirmed by this result.

[Fiver]

Exactly! I'm trying to find data to tell if more commonly used - and less expensive - approaches to TNF-a inhibition might work equally well. I assume not, since there must have been some real incentive to develop these biologics in he first place. But maybe stacking multiple anti-inflammatory strategies could get close.

[broiler_x]

I've been following this story. I don't fault Pfizer for not pursuing this, it doesn't sound like there was enough of a positive signal to warrant the cost of a PhIII clinical trial. Those trials are really expensive, especially for AD due to the necessary long duration and high mortality of the aged treatment group which necessitates large numbers. It sounds like this idea was thoroughly vetted, and even outsiders agreed that the positive signal was very small. Add on to all of that the immense and very expensive failures of biologics clinical trials in AD, and it didn't make any sense. I think the only valid criticism of Pfizer is not sharing these findings with the scientific community so that others could try and pursue this line of research. But having worked in the industry for 25 years, I know there is very little incentive to publish - especially mediocre or negative data. There is nothing in it for the company and it takes up resources. It's sad, but true. At the very least, they should have just given the data to academic experts and have them follow-up and publish on it.

Anyway, I hope it's true. I don't see a clear mechanism-of-action, but there might be something. I think microglial cells somehow hold the key, and there is more and more data supporting that. There is an interesting association between macrophages in the periphery (outside of the CNS) and microglia, so that could be a link.