Table 2.

Outcomes of phase II and III clinical trials of approved agents and donanemab (under review)

Agent	Trial NCT	Phase	Primary outcome	Biomarker outcomes
Aducanumab	02477800 (Study 301) ENGAGE [2]	III	High-dose CDR-SB: drug-pbo difference 0.03 (2%) [− 0.26, 0.33]; p = 0.833	Amyloid PET SUVR: drug-pbo difference − 0.232, p < 0.0001 Amyloid PET CL: drug-pbo difference − 3.5, p < 0.0001 CSF p-tau (pg/mL): drug-pbo difference − 13.19, p = 0.3019 CSF t-tau (pg/mL): drug-pbo difference −69.25, p = 0.3098
Aducanumab	02484547 (Study 302) EMERGE [2]	III	High-dose CDR-SB: drug-pbo difference − 0.39 (− 22%) [− 0.69, − 0.09]; p = 0.012	Amyloid PET SUVR: drug-pbo difference − 0.278, p < 0.0001 Amyloid PET CL: drug-pbo difference − 64.2, p < 0.0001 CSF p-tau (pg/mL): drug-pbo difference − 22.44, p = 0.0005 CSF t-tau (pg/mL): drug-pbo difference − 112.05, p = 0.0088
Donanemab	03367403 [5]	II	iADRS: drug-pbo difference 3.2 ± 1.56; p = 0.04	Amyloid PET: drug-pbo difference – 85.06 CL
Donanemab	04437511 [66]	III	iADRS: Intermediate tau population: 40% less decline in drug vs. placebo; p < 0.001 Combined tau populations: 23% less decline in drug vs. placebo; p < 0.001	Amyloid PET: Intermediate tau population: 34% of participants achieving Aβ clearance at 6 months; 71% of participants achieving Aβ clearance at 12 months
Lecanemab	01767311 [3]	IIb	ADCOMS (12 months, 10BW): LS mean drug-pbo difference − 0.046 (90% CI − 0.079, − 0.012); p = 0.027	Amyloid PET (18 months, 10 mg/kg combined); LS mean drug-pbo difference − 0.253; p < 0.001
Lecanemab	03887455 [4]	III	CDR-SB: drug-pbo difference − 0.45 (95% CI − 0.67, − 0.23); p < 0.001	Amyloid PET: drug-pbo difference − 59.12 CL (95% CI − 62.64, − 55.6); p < 0.001

ADCOMS Alzheimer’s Disease Composite Score, BW biweekly treatment, CDR-SB Clinical Dementia Rating–Sum of Boxes, CL centiloids, CSF cerebrospinal fluid, iADRS integrated Alzheimer’s Disease Rating Scale, LS least squares, pbo placebo, PET positron emission tomography, SUVR standardized uptake value ratio