Washington University School of Medicine
Neurology
Eric McDade, DO, is an Associate Professor of Neurology at the Washington University School of Medicine in St. Louis. His research interests include the application of cerebrospinal fluid and neuroimaging measures to identify early pathology of Alzheimer’s disease, the interaction of cerebrovascular function and Alzheimer pathology with the ultimate goal of identifying early markers of Alzheimer’s disease progression that can be used in testing disease modifying therapies. Dr. McDade serves as the Associate Director of the Dominantly Inherited Alzheimer’s Disease Trials Unit and the Clinical Core Leader of the Dominantly Inherited Alzheimer Network Observational Study where he and his colleagues are using a global, natural history study to develop prevention trials to in Dominantly Inherited AD. As part of this work he is the Principle Investigator of the first ever primary prevention trial in familial Alzheimer disease which will test whether preventing the development of amyloid plaques will prevent the development of dementia in those with a genetic form of the Alzheimer’s disease that leads to young-onset dementia.

Presenter of 1 Presentation

PHASE 2 LECANEMAB EARLY ALZHEIMER’S DISEASE STUDY BIOMARKER RESULTS AND CORRELATIONS WITH CLINICAL OUTCOMES

Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
05:15 PM - 07:15 PM
Room
ONSITE PLENARY: 115-117
Lecture Time
05:55 PM - 06:10 PM

Abstract

Aims

Key fluid biomarker findings and their correlations with clinical outcome from the phase 2 lecanemab 201 trial (Core and open-label extension [OLE]) will be discussed. PET, CSF and plasma was used to assess longitudinal biomarker changes during the double-blind Core portion of the trial while patients were receiving placebo or treatment, after discontinuing treatment, and on resuming treatment. The Tau NexGen trial (part of the Dominantly Inherited Alzheimer Network Trials Unit [DIAN-TU]) evaluating lecanemab combined with E2814 (anti-MTBR tau) will also be highlighted.

Methods

Multimodal data accumulated for biomarkers, eg. amyloid, p-tau181, neurogranin, and neurofilament light (NfL) from the lecanemab Study 201 (Core and OLE) was analyzed and correlated with clinical outcomes. Samples of plasma and CSF, amyloid PET scans, and clinical outcomes across a duration of up to 5 years were utilized in the analysis.

Results

Correlation can be seen between clinical outcomes, amyloid PET SUVr & plasma Aβ42/40 ratio / pTau181 across 18 months of treatment. When treatment was discontinued for average of 2 years, these correlations were low. When treatment was re-initiated, there was return to earlier treatment effect on clinical outcomes as well as all the biomarkers.

Conclusions

Treatment with lecanemab in early AD was associated with change in CSF, plasma biomarkers, and amyloid PET, which were differentially correlated with clinical outcomes and response to therapy. Changes in multiple biomarkers following lecanemab treatment suggest a potential disease modifying effect. The DIAN-TU trial will utilize lecanemab as the background anti-amyloid therapy.

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