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
GSK3 inhibitor
Tideglusib (NP12)
2012.6
306
45 weeks
Missed its primary endpoint and some secondary endpoints