On the horizon-the value and promise of the global pipeline of Alzheimer's disease therapeutics.
Introduction
The recent failure of several late-stage Alzheimer's disease (AD) clinical trials focused on amyloid beta (Aβ) highlights the challenges of finding effective disease-modifying therapeutics. Despite major advances in our understanding of the genetic risk factors of disease and the development of clinical biomarkers, and that not all Aβ-based approaches are equivalent, these failures may engender skepticism regarding the value of the AD pipeline.


Methods
To investigate these concerns, we compiled a database of current Phase 2 and 3 trials based on disease-modifying targets through a query of the National Institutes of Health's ClinicalTrials.gov. We then assessed the financial value of the pipeline. Financial modeling utilized risk-adjusted net present value (rNPV) measurements and included sensitivity analyses to help inform the drug development process.


Results
Results indicate that the preponderance of current Phase 3 trials were indeed targeting Aβ, with only 15% addressing other targets. In contrast, the pipeline of Phase 2 trials was more diverse. The estimated rNPV of Phase 2 and 3 therapeutics was estimated to be $338 billion over 10 years. This figure increased to a theoretical cumulative value of $788 billion when incorporating the assumption that diagnostics will be developed to identify individuals at high risk for developing AD. Results from model sensitivity analyses showed that speed of market penetration and patient access contributed the most weight to financial value. In contrast, decreasing drug development costs had minimal impact on rNPV.


Discussion
These findings argue in favor of conducting thorough biomarker-driven Phase 2 proof of concept studies to avoid prematurely advancing assets into Phase 3. Insights from these analyses are also discussed in the context of the financial ecosystem needed to maintain a healthy AD pipeline.
['Cole|Michael A|MA|', 'Seabrook|Guy R|GR|']
Alzheimer's disease AD clinical trials biomarkers Phase 2 Phase 3 Phase 1 advocacy biotechnology companies dementia disease‐modifying therapy pharmaceutical industry prodromal AD