Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyond β-Amyloid: Insights from Clinical Trials

Table 4

Terminated trials targeting Aβ hypothesis.

Mechanism	RCT	End	Enrollment	Duration	Main reasons
BACE1 inhibitor	Rosiglitazone	2009.2	693	24 weeks	Unimproved cognitive status
	LY2886721	2013.8	128		AE: 4 cases of liver damage in a phase 2 study in June 2013
GSI/GSM	Semagacestat	2011.5	164	>7 months	Unimproved cognitive status, but worsening functional ability; AE: skin cancers and infections
	Avagacestat	2010.6	209	24 weeks	AE: gastrointestinal and dermatological abnormalities like diarrhea, nausea, vomiting, rash, and itching skin; nonmelanoma skin cancers; and worsened cognition
	tarenflurbil	2008.5	1684	18 months	Insufficient pharmacodynamics: poor capability to penetrate the BBB
Active immunology	AN1792	2003.9	375		AE: 6 patients developed aseptic meningoencephalitis due cytotoxic T cell response in phase 2a trial
	ACC-001	2014.2	126	24 months	Showed a serious side effect in phase 2 trial
Passive immunology	Bapineuzumab (AAB-001)	2012.6	1331	18 months	Showed no treatment effect on either cognitive or functional outcomes in two phase 3 trials
GSK3𝛽 inhibitor	Tideglusib (NP12)	2012.6	306	45 weeks	Missed its primary endpoint and some secondary endpoints

RCT: randomized controlled trial; AE: adverse event; BBB: blood brain barrier.
Data sources: http://www.clinicaltrials.gov/; http://www.alzforum.org/.