In February 2018 the U.S. Food and Drug Administration (FDA) made a giant leap in modernizing its approach to its evaluation for new drugs for Alzheimer’s disease and other neurologic disease. This is welcome news to researchers who are searching for medications to treat these conditions.

For many years, the standard for a new drug for Alzheimer’s disease has focused on generating evidence that any new therapy being studied could slow the cognitive decline of the patients and help preserve their daily functions that can keep a patient independent for a longer period of time. According to an article published in STAT in March of this year, impairments in cognition — which includes memory, executive function, language and other aspects of thinking and reasoning, are the distinctive features of Alzheimer’s. Whereas functional impairments — problems with daily tasks such as dressing and personal hygiene, cooking, driving, etc, are generally due to cognitive issues.

However, these two requirements are not in line with our current understanding of the disease and likely lead to the high failure rate in Alzheimer’s drug trials. We can now recognize earlier stages of Alzheimer’s disease, known as mild cognitive impairment, where patients have no issues with daily function. In this enormous group of patients, it’s almost impossible to show improvements in function because their function is years away from being compromised.

In a new set of guidelines, the agency proposed to offer an approval pathway for new drugs that could prevent the onset of the devastating symptoms of Alzheimer’s if drug developers could hit acceptable biomarkers that indicate the drug is working. They will also adopt a new standard that focuses on long-term cognition alone, without the previous function requirement, lowering the bar for drugs requirements. In the new draft guidelines, the FDA recognizes and outlines the three stages of early Alzheimer’s disease and offers guidance on drug development for each. These forward-thinking guidelines line up with the recent advances in our understanding of Alzheimer’s.

Stage 1 Alzheimer’s: These individuals have no clinical symptoms of the disease, but do have biomarker (a biomarker is a measurable indicator of some biological state or condition) evidence of it via positive PET scans of the brain and/ or positive tests for beta-amyloid or tau. These are the two proteins that are hallmarks of Alzheimer’s disease. According to the STAT article, for clinical trials involving these asymptomatic, cognitively normal patients, the FDA says that improvements in relevant biomarkers could now serve as the basis for accelerated drug approval.

Stage 2 Alzheimer’: Patients in this stage 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: These patients have biomarker evidence of the disease plus the previously required combination, cognitive and functional impairment. This the the stage that is currently labeled “mild cognitive impairment.” The FDA suggests that trials testing therapies in this group should include measures of cognition and function, but welcomes new approaches to assessing these outcomes.

The desire to study new drugs at an earlier stage of the disease, especially in the presymptomatic group, has been a priority for years now. Shifting away from the gold standard endpoints and toward an evolving set of biomarkers, definitive to each stage of the disease, is a step in the right direction. However, some caution that this could raise the prospect that the FDA will approve new drugs that don’t actually do anything to alter the course of the disease.

Mostly, this is welcome news for researchers, drug developers, and will contest attorneys alike. Hopefully, these new requirements will allow researchers and drug makers to develop appropriate medications that will forestall, or even prevent, the spread of this devastating disease. Furthermore, the development of a successful drug could help prevent will contest litigation on the basis of lack of testamentary capacity. If you enjoyed reading this, check out our blog on “Improving Alzheimer’s Diagnosis” for an in-depth discussion of how the disease can impact a will contest.

Alzheimer’s, Will Contests / Challenging a Will
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