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.