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 ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedDouble-Blind MethodFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedTreatment OutcomeConceptsOpen-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 ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedBrainFemaleHumansMalePositron-Emission TomographyConceptsAmyloid-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 differenceLecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer’s Disease
Cohen S, van Dyck C, Gee M, Doherty T, Kanekiyo M, Dhadda S, Li D, Hersch S, Irizarry M, Kramer L. Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer’s Disease. The Journal Of Prevention Of Alzheimer's Disease 2023, 10: 771-777. PMID: 37874099, DOI: 10.14283/jpad.2023.123.Peer-Reviewed Original ResearchConceptsZarit Burden InterviewPhase 3 trialEarly Alzheimer's diseaseAlzheimer's diseaseQoL-ADPartner burdenMean changeDouble-blind phase 3 trialCerebrospinal fluid evidenceHumanized IgG1 monoclonal antibodyMarkers of amyloidLife-5 DimensionsHealth-related qualityPhase 3 developmentCare partner burdenLess increaseCerebral amyloid accumulationLess declineYears of ageQuality of lifePositron emission tomographyMild cognitive impairmentIgG1 monoclonal antibodyValuable patientsBurden Interview
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 ResearchMeSH KeywordsActivities of Daily LivingAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedCognitionDouble-Blind MethodHumansNootropic AgentsConceptsEarly 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 antibodyTwo Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease
Budd Haeberlein S, Aisen P, Barkhof F, Chalkias S, Chen T, Cohen S, Dent G, Hansson O, Harrison K, von Hehn C, Iwatsubo T, Mallinckrodt C, Mummery C, Muralidharan K, Nestorov I, Nisenbaum L, Rajagovindan R, Skordos L, Tian Y, van Dyck C, Vellas B, Wu S, Zhu Y, Sandrock A. Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease. The Journal Of Prevention Of Alzheimer's Disease 2022, 9: 197-210. PMID: 35542991, DOI: 10.14283/jpad.2022.30.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedBiomarkersHumansConceptsEarly Alzheimer's diseasePhase 3 studyAlzheimer's diseaseDisease dementiaAmyloid betaDisease pathophysiologyRandomized phase 3 studyClinical Dementia Rating SumCommon adverse eventsSecondary clinical endpointsPrimary outcome measureDose-dependent reductionAlzheimer's disease pathophysiologyAlzheimer's disease dementiaHuman monoclonal antibodyMild cognitive impairmentMild Alzheimer's disease dementiaPrimary endpointSecondary endpointsWeek 78Adverse eventsBiomarker substudyClinical outcomesEfficacy analysisBackgroundAlzheimer’s disease
2012
Safety and biomarker effects of solanezumab in patients with Alzheimer's disease
Farlow M, Arnold SE, van Dyck C, Aisen PS, Snider BJ, Porsteinsson AP, Friedrich S, Dean RA, Gonzales C, Sethuraman G, DeMattos RB, Mohs R, Paul SM, Siemers ER. Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimer's & Dementia 2012, 8: 261-271. PMID: 22672770, DOI: 10.1016/j.jalz.2011.09.224.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedCognition DisordersDose-Response Relationship, DrugDouble-Blind MethodElectroencephalographyEnzyme-Linked Immunosorbent AssayFemaleFollow-Up StudiesHumansMaleMiddle AgedNeuropsychological TestsPeptide FragmentsPsychiatric Status Rating ScalesPyridinesTomography, Emission-Computed, Single-PhotonTreatment OutcomeConceptsAlzheimer's Disease Assessment Scale-cognitive portionAntibody administrationDose-dependent mannerAlzheimer's diseaseAntibody treatmentAnti-β-amyloid antibodiesPlacebo-controlled clinical trialMagnetic resonance imaging (MRI) scansCerebrospinal fluid examinationClinical laboratory valuesActive treatment periodCSF cell countResonance imaging scansModerate Alzheimer's diseaseDose-dependent increaseMagnetic resonance imagingWeekly infusionsAdverse eventsFluid examinationImaging scansClinical trialsLaboratory valuesTreatment periodAmyloid plaquesCell count