Table 4.
Cerebrospinal fluid Aβ lowering - summary of clinical trial results
| Name | Mechanism | Stage of development | NHVs | Patient population | Patient CSF Aβ a | Amyloid PET | Reference |
|---|---|---|---|---|---|---|---|
| AN1792 |
Active vaccine |
D/C (phase IIa) |
NR |
M-M |
No change |
NR |
[115] |
| Bapineuzumab |
Passive vaccine |
D/C ( phase III (i.v.); phase II (s.c.)) |
NR |
M-M |
No change |
Decrease |
[74,116] |
| Solanezumab |
Passive vaccine |
Phase III, pre-sym |
NR |
M-M, mild |
Total (40/42) - increased Unbound 42 - increased Unbound 40 - decreased |
NR |
[117,122] |
| Crenezumab |
Passive vaccine |
Phase I/II |
NR |
Pre-sym, FAD |
NR |
NR |
[127] |
| Gantanerumab |
Passive vaccine |
Phase II/III |
NR |
M-M, pre-dem |
NR |
Decrease |
[101] |
| IVIG |
Anti-inflammatory |
Phase III |
NR |
M-M |
No change |
NR |
[126] |
| Tarenflurbil |
GSM |
D/C (phase III) |
NR |
M-M |
NR |
NR |
[109] |
| Semagacestat |
GSI |
D/C (phase III) |
No change |
M-M |
No change |
NR |
[102-104] |
| Avagacestat |
GSI |
D/C (phase II) |
≥50% decrease |
M-M |
High dose: ~50% decrease Tolerated doses: ≤15% decrease |
NR |
[79,85,86] |
| LY2811376, LY2886721 |
BACE inhibitor |
D/C (phase II) |
≥50% decrease |
M-M |
NR |
NR |
[82] |
| MK8931 | BACE inhibitor | Phase II | NR | M-M | ≥80% decrease | NR | [99] |
aMost advanced stage clinical trial. Aβ, amyloid-β; BACE, β-site APP-cleaving enzyme; CSF, cerebrospinal fluid; D/C, clinical development discontinued; FAD, familial Alzheimer's disease; GSI, γ-secretase inhibitor; GSM, γ-secretase modulator; i.v., intraventricular; M-M, mild to moderate Alzheimer’s disease; NHV, normal healthy volunteer; NR, not reported; PET, positron emission tomography; pre-dem, predementia; pre-sym, presymptomatic; s.c., subcutaneous.