A recent review, written by Pieter van Bokhoven from the Industry Alliance Office of Amsterdam Neuroscience and colleagues looked into the landscape of Alzheimer’s disease (AD) drug development over the last 15 years. This review gives more insight into the status of AD drug development by comparing drugs in preclinical development to drugs currently tested in clinical trials.  

The research field investigating neurodegenerative diseases, such as Alzheimer’s disease has made significant progress over the last 15 years. Diagnoses has altered from a syndrome diagnose towards a biomarker construct. However, for the last couple of decades, drug development for AD has been proven to be difficult, and despite failures, the field has not lost confidence in drug development for AD. This review published by Van Bokhoven and colleagues compared drugs in preclinical development (by biotechnology or pharmaceutical companies) to drugs currently tested in clinical trials. They did this by analysing proprietary and public databases and company websites for drugs in preclinical development for AD and major clinical trial registries for drugs in clinical development for AD. These drugs were categorized by target class and treatment modality.

In the review, Van Bokhoven found a higher proportion of preclinical interventions targeting molecular pathways associated with sporadic AD genetic risk variants, compared to clinical stage interventions. These include apolipoprotein E (ApoE) and lipids, lysosomal/endosomal targets, and proteostasis. He also witnessed a trend suggesting that more traditional therapeutic modalities are developed for novel targets, such as apolipoprotein E and lipids, lysosomal /endosomal targets, and proteostatis. More novel treatment modalities such as gene therapies and enzyme treatments on the other hand are in development for more traditional targets such as amyloid B and tau. Interestingly, the percentage of amyloid β targeting therapies in preclinical development is even higher than the percentage in clinical development indicating that diversification away from interventions targeting amyloid-beta has not materialized. Inflammation is the second most popular target class in both preclinical and clinical development.

These observations show that the AD drug development pipeline is diversifying in terms of targets and treatment modalities, while amyloid-targeting therapies remain a prominent avenue of development as well.

Drug development for the complexity of AD is and will however remain a challenge. Continuing to invest in the diversification of drug targets and diagnostics will be the best hope for the next generation of AD drugs that will enter the clinical trials. 

Read the publication in BioMed: The Alzheimer’s disease drug development landscape