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Table 1 Update of selected anti-Alzheimer’s disease drugs in clinical trials (updated in June 2017)

From: Drug candidates in clinical trials for Alzheimer’s disease

Target Drug name Therapy type Trial status Reasons for Discontinuation Company Clinical Trial Identifier References
Serotoninergic
(5-HT6 receptor antagonist)
Idalopirdine Small molecule Phase III
Discontinued in 2017
No clinical efficacy H. Lundbeck, Otsuka Pharmaceutical Co., Ltd. NCT01019421
NCT02006641
NCT02006654
[13]
Intepirdine Small molecule Phase II/III Not applicable Axovant Sciences Ltd. NCT02910102 NCT02585934
NCT02586909
[14]
Histaminergic
(H3 receptor antagonist)
ABT-288 Small molecule Phase II Discontinued in 2011 No clinical efficacy AbbVie NCT01018875 [16]
GSK239512 Small molecule Phase II Discontinued in 2012 No improvements in memory test GlaxoSmithKline (GSK) NCT01009255 [17]
SUVN-G3031 Small molecule Phase I Not applicable Suven Life Sciences Ltd NCT02342041  
Acetylcholine response ↑
(α7nAChR agonist)
Encenicline Small molecule Phase III Discontinued in 2015 Adverse effects: gastrointestinal side effect FORUM Pharmaceuticals Inc., Mitsubishi Tanabe Pharma NCT01969136
NCT01969123
[23, 24]
Glutaminergic Riluzole Small molecule Phase II Not applicable Sanofi NCT01703117 [29,30,31,32]
BACE inhibitor BI 1181181 Small molecule Phase I Discontinued in 2015 Low oral bioavailability and low blood-brain barrier penetration Boehringer Ingelheim, Vitae Pharmaceuticals NCT02044406
NCT02106247
NCT02254161
 
RG7129 Small molecule Phase I Discontinued in 2013 Liver toxicity Roche NCT01664143
NCT01592331
 
LY2811376 Small molecule Phase I Discontinued
In 2008
Liver toxicity Eli Lilly & Co. NCT00838084  
LY2886721 Small molecule Phase II Discontinued
In 2013
Liver toxicity Eli Lilly & Co. NCT01561430 [36]
E2609 Small molecule Phase III Not applicable Biogen, Eisai Co., Ltd. NCT03036280
NCT02956486
 
AZD3293 Small molecule Phase III Not applicable AstraZeneca, Eli Lilly & Co. NCT02783573  
CNP520 Small molecule Phase II/III Not applicable Amgen, Inc., Novartis Pharmaceuticals Corporation NCT02576639
NCT02565511
 
JNJ-54861911 Small molecule Phase II/III Not applicable Janssen, Shionogi Pharma NCT02406027
NCT02569398
 
Verubecestat Small molecule Phase III Not applicable Merck NCT01953601 [37]
γ-Secretase inhibitor Semagacestat Small molecule Phase III Discontinued in 2012 No clinical efficacy and adverse effects: skin cancer and infections Eli Lilly & Co. NCT00762411
NCT00594568
NCT01035138
[40]
Avagacestat Small molecule Phase II Discontinued in 2012 Adverse effects: cerebral microbleeds,
glycosuria, and nonmelanoma skin cancer
Bristol-Myers Squibb NCT00890890  
EVP-0962 Small molecule Phase II
Discontinued in 2016
Not applicable FORUM Pharmaceuticals Inc. NCT01661673 [41]
NIC5-15 Small molecule Phase II Not applicable Humanetics Pharmaceuticals Corporation NCT00470418
NCT01928420
 
Aβ clearance AN-1792 Active immunotherapy
(Aβ1-42 peptides)
Phase II Discontinued in 2002 Adverse effects: meningoencephalitis Janssen, Pfizer NCT00021723 [44]
CAD106 Active immunotherapy
(Aβ1-6 peptides)
Phase II/III Not applicable Novartis Pharmaceuticals Corporation NCT01097096
NCT02565511
[47]
ACC-001 Active immunotherapy
(Aβ1-4 peptides)
Phase II Discontinued in 2013 Adverse effects: strong autoimmune response Janssen NCT01238991
NCT00479557 NCT00498602
[48]
Affitope AD02 Active immunotherapy
(6 a.a. peptides mimic Aβ1-42 N-terminus)
Phase II-discontinued in 2014 Not applicable AFFiRiS AG NCT01117818 [49]
Bapineuzumab Passive immunotherapy
(against Aβ N-terminal)
Phase III- discontinued in 2012 No clinical efficacy Janssen, Pfizer NCT00667810 NCT00676143 [50]
AAB-003 Passive immunotherapy Phase I Not applicable Janssen, Pfizer NCT01193608 NCT01369225  
GSK933776 Passive immunotherapy
(against Aβ N-terminal)
Phase I Discontinued in 2012 No clinical benefit GlaxoSmithKline (GSK) NCT00459550
NCT01424436
 
Solanezumab Passive immunotherapy
(against Aβ16-24)
Phase III
Discontinued in 2016
Missed primary endpoint Eli Lilly & Co. NCT01127633 NCT01900665 [51,52,53]
Crenezumab Passive immunotherapy
against Aβ)
Phase III Not applicable AC Immune SA, Genentech, Hoffmann-La Roche NCT02670083  
Gantenerumab Passive immunotherapy
(against Aβ3-12 & Aβ18-27)
Phase III Not applicable Chugai Pharmaceutical Co., Ltd., Hoffmann-La Roche NCT02051608
NCT01900665
 
BAN2401 Passive immunotherapy
(against large soluble Aβ protofibrils)
Phase II Not applicable Biogen, Eisai Co., Ltd. NCT01767311  
Aducanumab Passive immunotherapy
(against aggregated Aβ)
Phase III Not applicable Biogen NCT02477800
NCT02484547
[54]
Tau stabilization Epothilone D Small molecule Phase I Discontinued in 2013 Not applicable Bristol-Myers Squibb Not available  
TPI 287 Small molecule Phase I Not applicable Cortice Biosciences NCT01966666  
Tau aggregation inhibitor Rember™ Small molecule Phase II Discontinued in 2007 Adverse effects: diarrhea, urinary urgency, and painful urination, etc. TauRx Therapeutics Ltd NCT00515333
NCT00684944
[59, 60]
TRx0237 Small molecule Phase III Not applicable TauRx Therapeutics Ltd NCT01689233
NCT01689246
NCT01626378
[61]
p-Tau clearance AADvac-1 Active immunotherapy
(synthetic peptide truncated and misfolded tau)
Phase II Not applicable Axon Neuroscience SE NCT01850238
NCT02031198
NCT02579252
[61, 62]
ACI-35 Active immunotherapy
(Human protein tau sequence 393 to 408 of longest tau isoform
phosphorylated at S396 and S404)
Phase I Not applicable AC Immune SA, Janssen Main ID in the WHO International Clinical Trials Registry Platform: ISRCTN13033912 [61,62,63]
Microglial activation inhibitor Alzhemed™ Small molecule Phase III
Discontinued in 2007
No clinical efficacy Neurochem, Inc. Not available [64]
Azeliragon Small molecule Phase III Not applicable Pfizer, TransTech Pharma, Inc., vTv Therapeutics LLC NCT02080364  
Ibuprofen Small molecule Phase IV
Discontinued in 2005
No clinical efficacy Not applicable Not available [65]
Flurizan™ Small molecule Phase III Discontinued in 2008 No clinical efficacy Myriad Genetics & Laboratories NCT00322036  
CHF 5074 Small molecule Phase II Not applicable CereSpir™ Incorporated, Chiesi Pharmaceuticals Inc. NCT01421056 [66]