Looking back at your last decade tracking drugs, what are some lessons learned and what are some of the more exciting drug categories to emerge?
My answer to this question is: Biologics rule. The main successes have been in biologics, in the monoclonal antibodies against amyloid, like the two FDA-approved agents lecanemab and aducanumab. But I think that the monoclonals, while I’m really happy to have them, are a first step. If you look back at tacrine, the first drug approved in 1993 for Alzheimer’s disease, it was a very difficult drug with lots of side effects. But then within 3 years we had donepezil, which was a very benign drug. I feel that a similar evolution is likely with regard to these antibodies. The first ones, we know, have big challenges, and you learn from those challenges and you just keep improving them. But you have to start somewhere, and you have to validate that target. Now I think that amyloid is validated.
What other approaches are interesting to you?
We have seen dramatic imaging results with marked reductions in neurofibrillary tangles from an antisense oligonucleotide aimed at tau protein. And there are two very active areas in the pipeline: inflammation and synaptic plasticity. Each has roughly 20 drugs apiece in development across all phases. And as you know, both synaptic plasticity and inflammation are represented across neurodegenerative conditions.
Your annual report has always focused on drugs to treat Alzheimer’s disease. Will the new database cover other types of dementia and neurodegenerative diseases?
That’s an obvious next step. I’m hoping that late this year we will have funding to expand the database into frontotemporal lobar degenerations, which will include all the tauopathies. And there’s also an overlap with TDP-43 diseases, so we’ll bring all of that in too. We have a new initiative on Parkinson’s disease and dementia with Lewy bodies that I hope will materialize by next year. My goal is that this will eventually become a neurodegenerative disease therapies database. The really interesting drugs right now are being tested in more than one neurodegenerative disease, and we should look at those more carefully. It will be more feasible to do that if they’re on the same data set.
What about other therapy classes?
We aim to be more serious about devices.
What will you call the database?
The Clinical Trial Observatory. We may start by calling it the Alzheimer’s Disease Clinical Trial Observatory. But the intention, obviously, is to go way beyond Alzheimer’s disease. The database is managed by a terrific team of data scientists at Cleveland Clinic, led by Feixiong Cheng, PhD.
The annual pipeline report is very much associated with you. Is the database going to be different?
Right now, I’m like the grandfather of this project. I won’t be around forever. This will have to pass on, and we’re already talking about succession. We’re thinking about how to make sure this community resource continues to be a community resource. Also, over all these years the annual report reflected my perspective. But with a database, many more people will be able to share their perspectives. I happen to think that “biologics rule,” but others might look at the data, see different scientific currents, and draw different conclusions. That will create a rich dialogue.
Do you think your reports have changed people’s perspectives on Alzheimer’s disease therapies? There’s a widely held idea that the field is exclusively focused on amyloid, or even dead-ended, but the papers seem to show something different.
We think this effort has helped, and will continue to help and foster investment and growth in treatments for our patients. It really does show how diverse the clinical trials landscape is now. People are surprised to learn of the number and diversity of approaches. Just last week I was presenting at the Center for Brain Health in Dallas and there was a doctor in the audience who was a caregiver to his wife with Alzheimer’s disease. He came up afterwards and said, “I had no idea there were so many drugs in clinical trials,” because there’s no way to find out if you don’t know about this resource.
Dr. Cummings discloses consulting for a range of companies working in Alzheimer’s therapies and diagnostics, including Acadia, Alkahest, AlphaCognition, AriBio, Avanir, Axsome, Behren, Biogen, Biohaven, Cassava, Cerecin, Cortexyme, Diadem, EIP Pharma, Eisai, GemVax, Genentech, Green Valley, Grifols, Janssen, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Ono, Otsuka, PRODEO, ReMYND, Renew, Resverlogix, Roche, Signant Health, Suven, United Neuroscience, and Unlearn AI. He has received several grants from the National Institute on Aging.