The informed road map to prevention of Alzheimer Disease: A call to arms

McDade, Eric; Llibre-Guerra, Jorge J.; Holtzman, David M.; Morris, John C.; Bateman, Randall J.

doi:10.1186/s13024-021-00467-y

Molecular Neurodegeneration

Table 1 Current Aβ therapeutics with rationale for AD prevention clinical trials

From: The informed road map to prevention of Alzheimer Disease: A call to arms

Class	Compound	Current status	Disease Stage	Trial #/Names	Sample size	Trial Outcome measures	Evidence from clinical studies
Immuno-therapy	ABvac 40 (active vaccine)^a	Phase 2	Mild AD	NCT03461276	120^b	Safety and immune response	>90% immune response [44]
	ACI-24 (active vaccine)	Phase 2	Asymptomatic Down Syndrome	NCT04373616 ACI-24-0701	72^b	Safety and MRI	Initial formulation with suboptimal immune response
	BAN2410	Phase 2/3	Asymptomatic with low or higher amyloid plaque load	NCT01767311 AHEAD (A345)	856	Safety and Cognitive change	Active, results not yet available
	CAD106	Phase 3	Asymptomatic sporadic AD	NCT02565511	480	Cognitive change	Terminated, results not yet available
	Crenezumab	Phase 2	Asymptomatic DIAD	NCT01998841	252	Cognitive change	Low to High dose being tested in Colombian kindred (PSEN-1_E280A)
	Gantenerumab	Phase 2/3	Asymptomatic DIAD; Mild AD	NCT01760005 NCT03443973	73 982	Biomarker, Cognitive, and Clinical change	Tau and neurodegeneration biomarker improvements with lowered CSF tau, p-tau181, and NfL. No clinical benefit in DIAD at low dose. High dose continued testing in DIAN-TU OLE prevention trial
	Solanezumab	Phase 3	Asymptomatic DIAD completed Asymptomatic sporadic AD	NCT01760005 NCT02008357 A4	71 1150^b	Biomarker, Cognitive, and Clinical change	No tau or neurodegeneration biomarker improvements or clinical benefit in DIAD on low dose; asymptomatic sporadic AD prevention trial (A4) ongoing with higher dose
	UB-311 (active vaccine)^a	Phase 2	Mild AD	NCT02551809	43	Safety and immune response	>90% immune response with a good safety profile.
Small Molecule^c	PQ912 (Inhibitor of glutaminyl cyclase)	Phase 2	Early AD	NCT03919162	414^b	Safety, PK and clinical outcomes	Good safety profile; trends for cognitive benefit [45].
Small Molecule^c	BACEi JNJ-54861911 MK-8931 (verubecestat) E2609 (Elenbecestat) CNP520 LY3314814 Lanabecestat	Phase 3	Asymptomatic/Early AD	NCT02569398 NCT01953601 NCT03036280 NCT03131453 NCT02245737	557 1454 2212 1145 2218	Negative effects in cognition, decrease Aβ	Clinical studies halted due to safety concerns with rapid mild negative effects in cognition which may be reversable.

The table represents the recent approaches to Aβ therapeutics highlighting new mechanisms to be tested on prevention trials
^aPotential agents for primary prevention
^bPotential agents for primary/secondary prevention. Proposed potential as a prevention therapy is based on how likely the known mechanism of action aligns with the disease stage of Aβ-pathology (prevent Aβ aggregation or Aβ plaques removal), the known side effect profile (long term treatments likely required) and the available data on clinical efficacy
^cEstimated enrollment

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ISSN: 1750-1326

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