Table 1 Passive immunotherapy for AD in clinical Phases, adopted from[33], anti-Aβ antibodies in clinical Phases I - III

Bapineuzumab, humanized 3D6

N-terminus (aa 1-5)

Phase III: trials were halted after completion of two trials demonstrated a failure to meet primary outcome measures of cognition and activities of daily living

[41–43]

Solanezumab, humanized m266

central (aa 16-24), accessible only on soluble Aβ

Phase III: ongoing as preventive trial in familial AD (DIAN). Trials failed to meet their primary endpoints in cognition and activities of daily living. A subsequent analysis of mild AD patients pooled from both trials showed a significant effect on cognition.

[44–46]

Gantenerumab, full human mAb

N-terminal (aa 3-12) and C-terminus (aa 18-27)

Phase III: ongoing in prodromal AD patients (DIAN), amyloid reduction but also ARIAs were observed in Phase I.

[47, 48]

IVIG containing polyclonal NAbs-Aβ: Gammagard, Octagam, New Gam, Flebogamma

most NAbs-Aβ bind central and C-terminus as well as pathogenic conformations of Aβ (focus on dimers)

Phase III (Gammagard): ongoing, (improved cerebral glucose metabolism and cognitive stabilization of AD symptoms was shown in small clinical studies, too small for statistical evaluation)

[49–51]

Phase III (Plasmapheresis with infusion of 20% albumin and Flebogamma): ongoing

Phase II (Octagam): cognition endpoints not met, but improved cerebral glucose metabolism

Phase II (NewGam): ongoing

Crenezumab, humanized mMABT

conformational epitopes including oligomeric and protofibrillar forms, (aa 13-14 appears relevant)

Phase II: ongoing as long-term safety extension study.

[52]

Preventive trial in an extended family carrying a presenilin-1 mutation, which causes early onset AD planned for 2013.

BAN2401, humanized mAb158

binds large-size Aβ protofibrils (>100 kDa)

Phase II: ongoing

[53, 54]

GSK933776

N-terminus of Aβ

Phase I: two clinical trials for AD are completed and one for macular degeneration is ongoing. Further development for macular degeneration is in Phase II.

[55]

AAB-003, Fc-engineered Bapineuzumab

N-terminal (aa 1-5)

Phase I: ongoing. Lower toxicity (ARIAs) compared to Bapineuzumab is expected. Continuation as open-label extension study

[56]

SAR228810, humanized mAb 13C3

protofibrils, and low molecular weight Aβ

Phase I: ongoing

[57]

BIIB037/BART, full human IgG₁

binds insoluble fibrillar human Aβ

Phase I: ongoing in prodromal AD patients

[58, 59]