FDA standards for evaluating Alzheimer’s drugs have been considered outdated by researchers for a long time. Finally, in 2018, the FDA is modernizing its approach and Alzheimer’s patients will benefit. This is great news for researchers working to develop much-needed medications.
FDA Standards: Alzheimer’s Drug Protocols
Since the 1990’s the FDA required that clinical trials show that a new drug for Alzheimer’s disease improved patients’ cognition and function. However, cognition and function improvements are not in line with current understanding of Alzheimer’s. Showing that a drug improved both metrics may be the reason for the high failure rate in Alzheimer’s drug trials.
Cognition impairments which includes memory failure, language difficulty, cloudy thinking and reasoning, are hallmarks of Alzheimer’s disease.
Functional impairments which includes dressing, cooking, driving, etc. are not markers for Alzheimer’s disease.
Thus, the FDA required drug developers to demonstrate improvements in function. But in the earlier stages of Alzheimer’s disease, mild cognitive impairment patients have no issues with daily function. In this large group of patients, it’s difficult, if not impossible, to show improvements in function because their function is fine. Hence, what otherwise might turn out to be a promising drug, fails.
Indeed, for other neurologic diseases, the FDA has required and continues to require clinical trials to focus on one endpoint. It is now finally applying this approach to Alzheimer’s drug protocols.
FDA Standards: New Drug Protocols For Alzheimer’s
The FDA’s new draft guidelines outline three distinct stages of early Alzheimer’s disease and offers clear guidance on drug development for each. These protocols acknowledge advances in our understanding of Alzheimer’s.
Stage 1 Alzheimer’s:
Individuals with stage 1 Alzheimer’s have no clinical symptoms of the disease, but show biomarker evidence of it. These can include positive PET scans of the brain for beta-amyloid or tau. These proteins are two clear signs of Alzheimer’s disease. For clinical trials involving these cognitively normal patients, the FDA will accept reductions in beta-amyloid or tau levels as the basis for accelerated drug approval.
Stage 2 Alzheimer’s:
Individuals with stage 2 Alzheimer’s have biomarker evidence of the disease and subtle cognitive impairment, but no problems with function. For trials in this population, the FDA will now consider “strongly justified arguments” for using only cognition as an endpoint.
Stage 3 Alzheimer’s:
Individuals with stage 3 Alzheimer’s have biomarker evidence of the disease plus cognitive and functional impairment. This is currently called mild cognitive impairment. The FDA suggests that trials testing therapies in this group should include measures of cognition and function, but encourages new approaches to assessing these outcomes.
FDA Standards: Designing The New Alzheimer’s Drug Protocols
The question now is how to design new Alzheimer’s clinical trials to meet these guidelines.
It’s clear that trials must now define the stage of Alzheimer’s disease among the population being studied at the time of enrollment, as well as the expected drug results.
The new FDA guidelines are a big advance. They define earlier stages of Alzheimer’s, acknowledge the vital role of biomarkers, and open doors for novel drug targets. The guidelines are there to develop new biomarkers and more sensitive tests of cognition and function.
The modernization of FDA requirements for researchers to receive approval for developing new Alzheimer’s drug therapies will hopefully lead to a cure.