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 | |
Glutaminergic | Riluzole | Small molecule | Phase II | Not applicable | Sanofi | NCT01703117 | |
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 | ||
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 | |
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 | |
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 | ||
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] |