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Table 1: Summary of anti-amyloid monoclonal antibodies in clinical trials
Monoclonal Antibody Aβ Binding Site Amyloid Target Completed Phase III Trials Main Results ARIA-E Incidence^{^a} ARIA-H Incidence^{^a} Active Phase III Trials
Aducanumab (Salloway et al, 2022) N-terminus conformational epitope Aβ oligomers, fibrils, and plaques EMERGEENGAGE Reduced decline in cognitive end pointsIncrease in CSF Aβ42Decrease in amyloid PET SUVR and CSF p-tau 35.2%20.3% NC43.0% C mH 19.1%12.4% NC22.7% CSS 14.7%6.2% NC19.1% C EMBARKTRAILBLAZER-ALZ-4
Bapineuzemab (Salloway et al, 2014)²⁸ N-terminus Aβ monomers, oligomers, and fibrils NCT00574132NCT00575055 No effect on cognitive end pointsDecrease in amyloid PET SUVR and CSF p-tau in APOEε4 carriers 4.2% NC15.3% C – –
Crenezumab (Guthrie et al, 2020)²⁹ Aβ peptides Aβ oligomers, fibrils, and plaques CREADCREAD 2 No effect on cognitive end points, amyloid PET or CSF p-tauIncrease in CSF Aβ42 0% 4.9% –
Donanemab (Mintun et al (2021)¹⁸ Pyroglutamate form of Aβ Aβ plaques TRAILBLAZER-ALZ-2 Reduced decline cognitive end pointsDecrease in amyloid PET SUVR 27.5%11.4% NC44.0% C 30.5% TRAILBLAZER-ALZ-3TRAILBLAZER-ALZ-4
Ponezumab (Landen et al, 2017)³⁰ C-terminus Soluble Aβ1-40 – No effect on cognitive end points, CSF Aβ42 or amyloid PET 0.7% 16.4% –
Gantenerumab (Ostrowitzki et al, 2017)³¹ N-terminus and central amino acids Aβ oligomers, fibrils, and plaques SCarlet RoADMarguerite RoAD No effect on cognitive end points or CSF Aβ42Decrease in amyloid PET SUVR and CSF p-tau 13.5%11.0% NC15.0% C 16.2%11.0% NC19.4% C GRADUATE 1GRADUATE 2DIAN-TU
Lecanemab (Swanson et al, 2021)¹⁹ Aβ protofibril Aβ protofibrils Reduced decline in cognitive end pointsIncrease in CSF Aβ42Decrease in amyloid PET SUVR and CSF p-tau 9.9%8.0% NC14.3% C 10.7%4.6% NC13.1% C CLARITY ADAHEAD 3–45
Solanezumab (Doody et al, 2014)³² Mid-domain Aβ monomers EXPEDITION 1EXPEDITION 2EXPEDITION 3EXPEDITION PRO No effect on cognitive end points, amyloid PET SUVR, or CSF p-tauIncrease CSF Aβ42 0.9% 4.9% A4DIAN-TU
Note:—mH indicates microhemorrhage; SS, siderosis; NC, APOEε4 noncarrier; C, APOEε4 carrier; SUVR, standardized uptake value ratio; –, none or not reported.
↵a ARIA incidence reported for the highest dose in studies with variable dosing arms. ARIA incidence reported for all participants and separately for APOEε4 noncarriers and carriers when data are available.