Alzheimer’s Disease: 2019 Refresher and Updates

Doc Gumshoe's updated look at the "Grey Plague"

By Michael Jorrin, "Doc Gumshoe", October 2, 2019

From where I sit, it seems to me that the entire landscape of Alzheimer’s disease (AD) has changed, and changed quite significantly.   The litany of announcements from pharmaceutical companies big and small revealing the unfortunate news that yet another promising agent for the treatment of AD has failed to meet its objectives in a clinical trial and is being withdrawn from the “race” to approval, is familiar and increasingly depressing.   The most recent and perhaps most disappointing of these were the failures of two BACE-1 inhibitors, one in a Phase III trial, the other in a Phase IIb/III trial.   I have discussed those two drugs, and, especially, their highly promising mode of action, in a previous encyclical, and there will be more to say later on in this one.

These failures, along with the many, many other failures to launch an effective drug for the treatment of AD, have had a dampening effect on AD research.   For example, AD deaths have increased by 145% in the years from 2000 to 2017.   Meantime, cancer deaths were declining; age-adjusted cancer mortality in the US declined by 26% from 1991 to 2015.   But venture-capital funding for cancer during those overlapping years was much higher than for AD – $16.5 billion for cancer in the past 10 years versus $1.0 billion for AD.   

You can’t exactly blame the moneybags guys for their reluctance to bet on a proposition where the odds are at least 20 to 1 against scoring a hit.   Those odds are calculated based on the fact that only four (five if you count a combo) drugs are FDA approved for AD, versus the hundred-plus flops.   And the odds are probably even worse, considering that none of the approved drugs do more than slightly delay the progression of dementia, and a couple were already approved for Parkinson’s disease.   So, if financial gain is the supposed motivation for investing in AD research, you can see why research into new drug development is slowing down.

However, AD continues to receive considerable support from the Federal government.   An additional $350 million were just added to the NIH budget specifically for AD research, bringing the total AD funding for the year 2020 to $2.8 billion.   Overall, despite opposition From Above, Congress increased NIH funding for 2020 by about $3 billion, bringing the total funding to $42.1 billion.

Much of that funding supports scientific research into Alzheimer’s rather than specific drug development.   And there’s a great deal of that going on.   According to PubMed, there are more than 149,000 papers on AD, and according to the Clinical Trials registry, more than 2,000 clinical trials in various phases.   What we’re not seeing are clinical trials of drugs in later phases with the objective of treating dementia in persons with established Alzheimer’s disease.

Before we get into the details, here’s an overview of the impact of AD in the US and the world.