2024
Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease
Honig L, Sabbagh M, van Dyck C, Sperling R, Hersch S, Matta A, Giorgi L, Gee M, Kanekiyo M, Li D, Purcell D, Dhadda S, Irizarry M, Kramer L. Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 105. PMID: 38730496, PMCID: PMC11084061, DOI: 10.1186/s13195-024-01441-8.Peer-Reviewed Original ResearchConceptsOpen-label extensionInfusion-related reactionsIntracerebral hemorrhageAdverse eventsAmyloid-related imaging abnormalitiesARIA-HParallel-group studyClinical laboratory parametersMonths of treatmentMild-to-moderateMagnetic resonance imagingHomozygous participantsAPOE e4 carriersDouble-blindPlacebo-controlledLaboratory parametersStudy treatmentARIA-E.Imaging abnormalitiesOptimal patient carePhysical examinationSafety resultsClinical trialsHemosiderin depositionResonance imaging
2023
Trial of Solanezumab in Preclinical Alzheimer’s Disease
Sperling R, Donohue M, Raman R, Rafii M, Johnson K, Masters C, van Dyck C, Iwatsubo T, Marshall G, Yaari R, Mancini M, Holdridge K, Case M, Sims J, Aisen P. Trial of Solanezumab in Preclinical Alzheimer’s Disease. New England Journal Of Medicine 2023, 389: 1096-1107. PMID: 37458272, PMCID: PMC10559996, DOI: 10.1056/nejmoa2305032.Peer-Reviewed Original ResearchConceptsAmyloid-related imaging abnormalitiesPreclinical Alzheimer's diseasePositron emission tomographyBrain amyloid levelsPlacebo groupAmyloid levelsAlzheimer's diseaseF-florbetapir positron emission tomographyGlobal Clinical Dementia Rating (CDR) scoreMini-Mental State ExaminationPrimary end pointClinical Dementia Rating scorePhase 3 trialPreclinical Alzheimer's cognitive composite scoresDementia Rating scoreYears of ageForms of amyloidBrain positron emission tomographyImaging abnormalitiesCognitive composite scoreMean ageFamily historyMean changePersons 65State ExaminationInvestigating Partially Discordant Results in Phase 3 Studies of Aducanumab
Mallinckrodt C, Tian Y, Aisen P, Barkhof F, Cohen S, Dent G, Hansson O, Harrison K, Iwatsubo T, Mummery C, Muralidharan K, Nestorov I, Nisenbaum L, Rajagovindan R, von Hehn C, van Dyck C, Vellas B, Wu S, Zhu Y, Sandrock A, Chen T, Budd Haeberlein S. Investigating Partially Discordant Results in Phase 3 Studies of Aducanumab. The Journal Of Prevention Of Alzheimer's Disease 2023, 10: 171-177. PMID: 36946443, DOI: 10.14283/jpad.2023.6.Peer-Reviewed Original ResearchConceptsHigh-dose armAmyloid-related imaging abnormalitiesPhase 3 studyBaseline characteristicsImaging abnormalitiesAlzheimer's diseaseDiscordant resultsParallel-group studyHigh-dose groupMild AD dementiaEarly Alzheimer's diseaseMild cognitive impairmentSecondary endpointsTreatment armsAD dementiaAmyloid pathologyMulticenter studyRapid progressionSignificant treatment effectSafety resultsTarget dosePatientsAducanumabCognitive impairmentNon-significant difference
2022
Lecanemab in Early Alzheimer’s Disease
van Dyck C, Swanson C, Aisen P, Bateman R, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer L, Iwatsubo T. Lecanemab in Early Alzheimer’s Disease. New England Journal Of Medicine 2022, 388: 9-21. PMID: 36449413, DOI: 10.1056/nejmoa2212948.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseasePositron emission tomographyDisease Assessment ScaleAlzheimer's diseaseAmyloid burdenAlzheimer's Disease Cooperative Study-ActivitiesAmyloid-related imaging abnormalitiesKey secondary end pointEnd pointAlzheimer's Disease Assessment ScaleClinical Dementia Rating SumHumanized IgG1 monoclonal antibodyMarkers of amyloidInfusion-related reactionsPrimary end pointSecondary end pointsCerebrospinal fluid testingPhase 3 trialBrain amyloid burdenDaily Living ScaleEvidence of amyloidCDR-SB scoresYears of ageMild cognitive impairmentIgG1 monoclonal antibody
2017
Anti-Amyloid-β Monoclonal Antibodies for Alzheimer’s Disease: Pitfalls and Promise
van Dyck CH. Anti-Amyloid-β Monoclonal Antibodies for Alzheimer’s Disease: Pitfalls and Promise. Biological Psychiatry 2017, 83: 311-319. PMID: 28967385, PMCID: PMC5767539, DOI: 10.1016/j.biopsych.2017.08.010.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAmyloid-related imaging abnormalitiesPutative disease-modifying treatmentsMonoclonal antibodiesOngoing prevention trialsDisease-modifying treatmentsPresymptomatic Alzheimer's diseaseImaging abnormalitiesPrevention trialsClinical efficacyPassive immunizationClinical trialsTherapeutic approachesDisease processPreclinical stageAβ-MAbNew trialsDiseaseAdditional studiesTrialsBest treatmentMAbsTreatmentAntibodiesConformation of Aβ