Listening session with the US Food and Drug Administration, Lewy Body Dementia Association, and an expert panel

Abstract

The regulatory path for drug approval is increasingly well defined. Drugs for the treatment of Alzheimer disease (AD) need to show statistically significant benefit over placebo with respect to cognitive and functional measures, with the Clinical Dementia Rating scale and Alzheimer's Disease Assessment Scale-Cognitive Subscale being among the most often used instruments in AD clinical trials. In contrast, there are no validated instruments for use in clinical trials of drugs for the treatment of dementia with Lewy bodies. This poses challenges for drug development because the regulatory pathway to drug approval requires demonstrable efficacy measures. In December 2021, the Lewy Body Dementia Association advisory group met with representatives from the US Food and Drug Administration to discuss the lack of approved drugs and treatments, discernment of efficacy measures, and identification of biomarkers.

The Parkinson's Disease Composite of Executive Functioning

“…45 DLB is clinically defined by the presence of dementia in addition to 1 (possible DLB) or at least 2 (probable DLB) core features (i.e., fluctuating cognition, visual hallucinations, REM sleep behavior disorder, and parkinsonism), 46 although the distinction between PD and DLB is debated. 47 There are no disease-specific treatments currently approved for DLB by the US Food and Drug Administration 48 or the European Medicines Agency, but there is growing interest in DLB drug development 49 with cognition being the target for 50% of DLB drugs currently in the development pipeline. 49 However, just as with PD, most DLB clinical trials are not using primary endpoints that are disease-specific or validated for the DLB population.…”

Clinical trials in dementia with Lewy bodies: the evolving concept of co-pathologies, patient selection and biomarkers

“…This is reflected in the recruitment to clinical trials for DLB which lacks uniformity and often includes additional diagnostic groups, usually PDD (Table 2). Recent expert consensus suggest that DLB and PDD could be included in clinical trials as separate, adequately powered groups, to allow identification of group differences [55]. Increasingly, clinical trials for DMTs are restricting their patient populations to DLB alone which likely reflects efforts to create a more homogenous group with less diverse pathomechanisms [6 & ].…”