Clinical Trials in Alzheimer’s Disease: A Hurdle in the Path of Remedy

Table 2

Recent clinical trial failures involving the beta-amyloid hypothesis.

Agent	Target/mechanism; [relevant references]	Trial phase	Reasons for failure	Comments
	Gamma secretase inhibitors
Semagacestat	[65]	III	Toxicity and lack of efficacy	Worsens cognition
Avagacestat	[66]	II	Toxicity and lack of efficacy
	Monoclonal antibodies to Aβ or its oligomers or fibrils
Bapineuzumab	[78]	III	Lack of efficacy	Asymptomatic amyloid-related imaging Aβ normalities
Aducanumab	[68, 69]	III	Futility analysis	Prediction that trials would not improve cognition
Solanezumab	[74]	III	Lack of efficacy	Also tested on prodromal AD
Gantenerumab	[79]	II	Lack of efficacy
Crenezumab	[75]	II	Lack of efficacy
	BACE-1 inhibitors
Verubecestat	[57]	III	Lack of efficacy	Worsens cognition
	[60]	III	Lack of efficacy	Tested on prodromal AD
Atabecestat	[61]	III	Toxicity	Worsens cognition
Lanabecestat	[62]	III	Lack of efficacy	Worsens cognition