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Table 1 Late-stage anti-amyloid agents: selectivity for amyloid oligomers and clinical and biomarker effects in phase 2 and 3 studies

From: Aducanumab, gantenerumab, BAN2401, and ALZ-801—the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval

Clinical and biomarker profile Biogen
Aducanumab
IV infusion 10 mg/kg monthly
Roche
Gantenerumab
SC injection monthly (225 mg and 1200 mg doses)
Eisai
BAN2401
IV infusion 10 mg/kg twice per month
Alzheon
ALZ-801/tramiprosate
Oral tablet 265 mg twice daily
Amyloid oligomer selectivity +/− +/− ++ +++
Blocks formation of oligomers
Study population Early AD
All genotypes
Early AD
All genotypes
Early AD
All genotypes
Early AD APOE4 carriers Mild AD
APOE4/4 homozygotes
Cognition
ADAS-cog (% benefit versus placebo)
27%
p = 0.0097
No effect 47%
p = 0.017
84%
Not reported
125%
p = 0.0001
Function
CDR-SB (% benefit versus placebo)
22%
p = 0.012
No effect 26%
p = NS
60%
Not reported
81%
p = 0.0197
CSF p-tau (% benefit versus placebo) 15% *31% 13% Not evaluated
Effects on other biomarkers Not reported *CSF t-tau
**CSF t-tau
**CSF NfL
CSF neurogranin, CSF NfL Preservation of hippocampal volume
Amyloid plaque removal +++ +++ +++ No plaque interaction
Brain edema ARIA-E (% of overall population and APOE4 carriers) 35% (all genotypes)
42% (APOE4)
$28%–#42% (all genotypes) 10% (all genotypes) 15% (APOE4) 0% (all genotypes)
0% (APOE4)
  1. Abbreviations: IV intravenous, SC subcutaneous, NS not significant, ADAS-cog Alzheimer’s Disease Assessment Scale—cognitive subscale, CDR-SB Clinical Dementia Rating—Sum of Boxes, ARIA-E amyloid-related imaging abnormalities with effusion or edema
  2. Assessment of amyloid oligomer selectivity: relative binding activity for soluble oligomers and protofibrils was measured by Biacore surface plasmon resonance. BAN2401 showed differential binding (KD) at 1.32 nM versus aducanumab 138 nM [10]; gantenerumab displays comparable affinity for oligomers and fibrils, and about 10× lower affinity for monomers [12]; ALZ-801/tramiprosate fully inhibits the formation of oligomer in the brain at target clinical dose [15]
  3. Data sources: aducanumab phase 3 studies [11, 19]; gantenerumab phase 3 studies at 225 mg SC and *DIAN-TU at mix of 225 mg SC and 1200 mg SC [13, 20, 21]; gantenerumab safety data: **phase 3 SCarlet RoAD study [13]; $Marguerite RoAD open-label extension study [22]; #amyloid PET open-label extension study [20]; BAN2401 phase 2 study [23]; ALZ-801: tramiprosate phase 3 study [15,16,17,18, 24]