Skip to main content

Advertisement

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

From: Passive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets?

mAb Specific for Clinical trials References
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 [4143]
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. [4446]
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) [4951]
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]
  1. (aa, amino acid; , Amyloid-β; ApoE4, ApolipoproteinE4; ARIA, amyloid-related imaging abnormalities; DIAN, Dominantly Inherited Alzheimer Network; IVIG, Intravenous Immunoglobulin; NAbs-Aβ, natural occurring polyclonal Anti-Aβ antibodies).