COMMENTARY

What Does Pfizer Backing Out of Alzheimer Research Mean to the Field?

Richard S. Isaacson, MD

Disclosures

February 27, 2018

Hi. My name is Richard Isaacson. I am director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian. I am reporting today for Medscape.

You may have heard the recent news about Pfizer. They are abandoning their entire Alzheimer disease (AD) portfolio. They are not doing any new drug discovery or investing in anything, and are going in a different direction.

There has been a lot of chatting about this and talk in coffee houses, doctor's lounges, and online about what this means for the field of AD. Does this mean that things are so bad that Pfizer is getting out? Maybe there is just no hope at all. I wanted to give a little bit of perspective, because that is not exactly the route that I go down when interpreting this.

As we all know, drug development takes years and years, and millions (sometimes billons) of dollars to go from the bench to the bedside. There have been a lot of failures. Around 90% of all Alzheimer's drugs have failed over the past couple of decades.[1] When a drug company says that they are just not going to invest all that time and money because of the 99% likelihood of failure, I think some people would understand that.

I look at this a little bit differently. We have many exciting drugs in the pipeline.[2] We have many clinical trials in phase 3 and even more clinical trials in phase 1 and phase 2. The philosophy is: more shots on goal. Amyloid and tau have been focused on as key pathologies of AD, but we are now trying to have more shots on goal and attack every single different mechanism to possibly reduce Alzheimer's risk or even reduce symptoms in the hope of a cure. Whether it is inflammation, infection, insulin resistance, or whatever else, we are really battening down the hatches and attacking all of these different areas.

I think Pfizer decided that there is a lot of research going on right now. There are a lot of companies invested with decades of infrastructure, and the pipeline looks pretty promising. Maybe it is not the best idea for Pfizer to invest more money into new drugs that may not pan out for the next 10 or 20 years or longer.

I am very excited about the horizon and about the way AD drug development is going. Many people look at the failures in the past as just terrible and that nothing will work. I do not necessarily agree with that because with every failure, you learn something. You learn that it did not work in a certain population, or that the dose was not high enough. Because of learning, whether on immunotherapies against amyloid or base inhibition against amyloid, there are now drugs being studied in multiple phase 3 trials where you can be infused or take a pill.

For decades, we did not have an adequate Alzheimer's biomarker. In an AD treatment trial, 40% of people enrolled did not have AD when they looked at biomarkers in the brain. They were amyloid-negative.[3] It is hard to have success in a research trial when you are attacking the amyloid protein, but 40% of the people in the trial did not have amyloid.

The other part about research failures is that sometimes we did not stratify correctly. For example, we are finding out that homozygotes for the APOE4 gene responded to tramiprosate. However, people who were not homozygous and were APOE4- negative did not respond at all.[4]

There have been advances with several amyloid-labeling agents, and tau imaging is on the horizon and even available in research settings. Not only will we have more shots on goal, but they will be much more accurate. They are going to get in the net much more frequently.

In the field of AD treatment, as well as prevention, when it comes to finding the right drug we need to find the right people to give that drug to. We are going to look at really interesting concepts of personalized medicine, precision medicine, and we are going to take multiple shots on goal using multiple different pathophysiologic mechanisms that may put you on the road to AD. We can debate whether amyloid or tau causes AD all day. I do think that certain conditions, certain pathophysiologic processes, can press the fast-forward button toward AD. If we can slam on the brakes instead of pressing fast-forward by reducing inflammation, reducing insulin resistance, or using a pharmaceutical drug, we will have a lot of great progress.

I am Richard Isaacson, here for Medscape. Thanks so much.

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