Marwan Sabag, M.D.: Dr. McDade, please give us an overview. We have a large pipeline of over 100 drugs that most people are not aware of. Many of them are DMTs. [disease-modifying therapies], many of them are monoclonals that target amyloid. Can you give us an overview and briefly explain the rationale for different epitopes in the pipeline and amyloid?
Eric McDade, DO: yes. Dr. Cohen’s one of the topics he mentioned, the difficulty of success we experienced, has forced us to be very broad in our approach to Alzheimer’s disease. The pipeline is currently very robust and broad, in contrast to what some believe is focused on amyloid. Their precise or more general approach applies to our standard pathology. Then there are these non-canonical pathways, and these may be something of an immune-inflammatory component. They may be related to the synaptic regeneration component of this. And beyond drug therapy, there is now a broader pipeline, including deep brain stimulation and more. There is research.
How many of them will succeed? Again, there are probably relatively few of them. But what has happened and what is evolving now is that we are in a better position to measure therapy. The long absence of these elements to treat Alzheimer’s disease has made it difficult to treat and has been thought to be an untreatable disorder. Currently, treatment is primarily monotherapy. Also becoming a distinct treatment paradigm evolving in Alzheimer’s disease is the realization that there are so many components to the symptoms that lead to an actual neurodegenerative component that there are probably multiple treatments. We will adopt more models that use different mechanisms targeting different pathways, such as those in oncology and cardiovascular disease. Their treatment is in progress.
Currently, the most successful therapeutic modality within the amyloid domain is immunotherapy targeting aggregated plaques. This data seems to support that lower amyloid plaque levels are more likely to provide clinical benefit. After failures such as gamma secretase inhibitors and base inhibitors, things like gamma secretase modulators are entering the field.Recently Approved Immunotherapies and Some of the Data Presented Here at CTAD [Clinical Trials on Alzheimer’s Disease conference]However, we are increasingly focusing on the aggregate plaque morphology of amyloid. Since then, some of these other amyloid-targeted therapies are still evolving.
Edited transcript for clarity