Presenter of 1 Presentation
PHASE 2 LECANEMAB EARLY ALZHEIMER’S DISEASE STUDY BIOMARKER RESULTS AND CORRELATIONS WITH CLINICAL OUTCOMES
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.