Interpreting Alzheimer’s disease clinical trials in light of the effects on amyloid-β

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.

ISSN: 1758-9193