Jeffrey L. Cummings, MD, ScD, The University of Nevada, Reno, NV, provides an overview of his key highlights from the AD/PD™ 2021 conference such as the Phase II TRAILBLAZER-ALZ study (NCT03367403), which utilised a novel study design and primary outcome measure to demonstrate that donanemab, a humanized IgG1 monoclonal antibody, significantly slowed Alzheimer’s disease (AD) progression. He also describes a range of exciting new technologies and analytical strategies presented at the meeting that could help enhance clinical trials, drug development and patient care in the future. This interview took place during the AD/PD™ 2021 conference.
Transcript (edited for clarity)
I came out way from ADPD with a tremendous amount of optimism. I think we saw new drugs and we saw new technologies. In terms of new drugs, donanemab of course stands out as a very promising agent and not only promising for its therapeutic purpose but also promising in terms of a new kind of trial. So the idea of using a tau ligand first and then if that was positive, the patient likely has Alzheimer’s disease...
I came out way from ADPD with a tremendous amount of optimism. I think we saw new drugs and we saw new technologies. In terms of new drugs, donanemab of course stands out as a very promising agent and not only promising for its therapeutic purpose but also promising in terms of a new kind of trial. So the idea of using a tau ligand first and then if that was positive, the patient likely has Alzheimer’s disease. Then doing the amyloid imaging that greatly reduced the screen fail rate on the amyloid imaging. And of course the high tau patients were eliminated. The drug was administered and it had a remarkable amyloid lowering effect and it met its primary outcome on the iADRS.
This was a novel outcome. The integrated Alzheimer’s disease rating scale, it’s basically a combination of the ADAS-Cog and the ADCS-ADL measure. So it is a functional cognitive composite. So again, we see novelty in the outcome. We see novelty in defining the population. We see novelty into therapeutic intervention. I think that’s just a terrific way of advancing clinical trials and therapeutics for Alzheimer’s disease.
ADPD also had a number of technologies that I thought were really fascinating and can contribute to clinical trials, drug development, and eventually have a role in clinical care. So among the things that I would highlight was the presentation from NQ, which is a way of passively measuring the speed with which someone is using a cell phone or their computer. And it’s shown to be sensitive to Parkinson’s disease, and now has been shown to be sensitive to early Alzheimer’s disease. And I think it’s that passive monitoring that is going to be important and the continuous monitoring that is going to be important.
Do I think that’s a new data strategy that’s attractive to me. I also like the Unlearn presentation. Unlearn is an machine learning and artificial intelligence approach that focuses on digital twins. So it is possible to create essentially an avatar of each of the members of the placebo group, and to increase the power of the trial or decrease the link or decrease the size of the trial by using the digital twins. So this of course is emerging. We don’t quite know how the regulators knew this yet, but this is a kind of technology that I think will amplify clinical trials.
Finally, I think some of the analysis that were done, I was fascinated by Suzanne Hendrick’s presentation. She talked about the ed comms, the Alzheimer’s disease composite score and this is a way of using the information collected on the standard CDR sum of boxes, the standard ADAS-Cog and the standard MMSE into a weighted score which then is sensitive to change.
In addition, she talked about the iADRS, which was used in the donanemab map trial. And she talked about the global statistical tasks, which I think is fascinating because it allows you to put several outcomes together. If the outcomes are internally consistent, the statistical power will increase if they’re really divergent and therefore there was some lack of coherence among the responses the statistical power will decrease. So I think those are extremely useful analytic strategies and this is what we need to advance new drug development and therapies for our patients with Alzheimer’s disease.
Dr. Cummings has provided consultation to Acadia, Alkahest, AriBio, Avanir, Axsome, Behren Therapeutics, Biogen, Cassava, Cerecin, Cerevel, Cortexyme, EIP Pharma, Eisai, GemVax, Genentech, Green Valley, Grifols, Janssen, Jazz, Karuna, Merck, Novo Nordisk, Otsuka, ReMYND, Resverlogix, Roche, Samumed, Samus, Signant Health, Sunovion, Suven, United Neuroscience, and Unlearn AI pharmaceutical and assessment companies.