TABLE 3.
Agents in Phase 1 of Alzheimer's disease drug development (ClinicalTrials.gov accessed February 27, 2020)
| Agent | CADRO mechanism class | Mechanism of action | Therapeutic purpose | Status(CT.gov ID) | Sponsor | Start date | Estimated end date |
|---|---|---|---|---|---|---|---|
| AAV‐hTERT | Epigenetic | hTERT delivered via transduction using AAV | Extending telomeres may benefit AD; reduce amyloid‐induced neurotoxicity; effects on multiple cellular pathways (DMT) |
Recruiting |
Libella gene therapeutics | Oct 2019 | Jan 2021 |
| AAVrh.10hAPOE2 | Epigenetic | Serotype rh. 10 AAV gene transfer vector expressing the cDNA coding for ApoE2 | Conversion of the ApoE protein isoforms in the CSF of ApoE4 homozygotes from ApoE4 to ApoE2‐ApoE4 (DMT) |
Recruiting |
Cornell University | Oct 2019 | Dec 2021 |
| AL002 | Inflammation | Monoclonal antibody targeting TREM2 receptors | Promote microglial clearance of amyloid and other toxic proteins (DMT) |
Recruiting |
Alector | Nov 2018 | Mar 2020 |
| AL003 | Inflammation | Monoclonal antibody targeting SIGLEC‐3 (CD33) | Reactivates microglia and immune cells in the brain; improve microglial clearance of toxic proteins (DMT) |
Recruiting |
Alector | Mar 2019 | Jul 2020 |
| Allopregnanolone (Allo) | Growth factors/hormones | GABA‐A receptor modulator; neurosteroid | Promote neurogenesis; reduce inflammation (DMT) |
Recruiting |
University of Southern California, University of Arizona, Alzheimer's Association | Oct 2019 | Oct 2020 |
| anle138b | Tau | Aggregation inhibitor |
Prevents/reduces aggregation of tau, α‐synuclein and prion proteins (DMT) |
Recruiting |
MODAG, quotient sciences | Dec 2019 |
Oct 2020 |
| BDPP (bioactive dietary polyphenol preparation) | Metabolism and bioenergetics, amyloid | Combination of grape seed polyphenolic extract and resveratrol | Prevents amyloid and tau aggregation (DMT) |
Recruiting |
Johns Hopkins University, Mount Sinai School of Medicine | Jun 2015 | Jun 2020 |
| BIIB076 | Tau | Monoclonal antibody | Remove tau and reduce tau propagation (DMT) |
Active, not recruiting |
Biogen | Feb 2017 | Mar 2020 |
| CT1812 | Synaptic plasticity/neuroprotection | Sigma‐2 receptor antagonist; competes with oligomeric Aβ binding | Preserve synaptic plasticity and protect against Aβ‐induced synaptic toxicity (DMT) |
Recruiting |
Cognition therapeutics | May 2018 | Mar 2021 |
| Dabigatran | Metabolism and bioenergetics, vasculature | Direct thrombin inhibitor | Reduce neurovascular damage (DMT) |
Not yet recruiting |
University of Rhode Island, ADDF, boehringer ingelheim | Nov 2018 | Dec 2021 |
| Efavirenz | Metabolism and bioenergetics, vasculature | Antiretroviral; non‐nucleoside reverse transcriptase inhibitor | Promote cholesterol removal from the brain and enhance amyloid reduction (DMT) |
Recruiting |
Case Western Reserve University, Cleveland Medical Center, Massachusetts General Hospital | May 2018 | Dec 2020 |
| Empagliflozin | Metabolism and bioenergetics | SGLT2 inhibitor | Improve glycemic control and enhance neuronal function (DMT) |
Recruiting |
NIA | Mar 2019 | Dec 2022 |
| Escitalopram and Venlafaxine | Neurotransmitter receptors | SSRI (escitalopram), SNRI (venlafaxine) | Improve neurotransmission (cognitive enhancer) |
Recruiting |
New York University | Jul 2017 | Jan 2020 |
| Fecal microbiota transplant (FMT) | Inflammation | Oral FMT intervention | Improve gut microbiota; reduce AD pathology (DMT) |
Recruiting |
University of Wisconsin, Madison | Nov 2019 | May 2022 |
| J147 | Metabolism and bioenergetics | Mitochondrial ATP synthase inhibitor | Increases use of free fatty acid to increase ketones for energy use; vascular protective effects (DMT) |
Recruiting |
Abrexa |
Jan 2019 | Jan 2020 |
| JNJ‐40346527 | Inflammation | CSF‐1R antagonist | Attenuates microglial proliferation and neurodegeneration (DMT) |
Not yet recruiting |
Janssen, University of Oxford | Nov 2019 | Nov 2021 |
| Lu AF87908 | Tau | Monoclonal antibody | Remove tau (DMT) |
Recruiting |
Lundbeck | Sep 2019 | Mar 2021 |
| MK‐4334 | Growth Factors and Hormones | Corticosteroid | Reduce inflammation (DMT) |
Not yet recruiting |
Merck | Sep 2019 | Feb 2020 |
| NNI‐362 | Neurogenesis | Nerve cell proliferation | Enhance neurogenesis; activates progenitor cells (DMT) |
Recruiting |
Neuronascent, NIA | Aug 2019 | Apr 2020 |
| RO7126209 | Amyloid | Monoclonal antibody; “brain‐shuttle” gantenerumab | Remove amyloid (DMT) |
Recruiting |
Roche | Aug 2019 | Jul 2020 |
| Salsalate | Inflammation | Non‐steroidal anti‐inflammatory | Reduce inflammation and neuronal injury (DMT) |
Recruiting |
University of California, San Francisco | Jul 2017 | Oct 2019 |
| Telmisartan | Vasculature | Angiotensin II receptor blocker | Improve vascular function with effects on amyloid pathology (DMT) |
Recruiting |
Emory University | Apr 2015 | Jun 2020 |
| TPI‐287 | Tau |
Tubulin‐binding and microtubule‐stabilization |
Reduce tau‐mediated cellular damage (DMT) |
Active, not recruiting |
University of California, San Francisco |
Nov 2013 |
Nov 2019 |
|
Tricaprilin (AC‐DS‐03) |
Metabolism and bioenergetics | Caprylic triglyceride; ketone body stimulant | Induce ketosis to improve mitochondrial metabolism (DMT) |
Recruiting |
Cerecin | Aug 2019 | Aug 2020 |
|
Not yet recruiting |
Cerecin | Feb 2020 | Jul 2020 | ||||
| Vorinostat | Epigenetic | Histone deacetylase (HDAC) inhibitor | Neuroprotection and enhanced synaptic plasticity (DMT) |
Recruiting |
German Center for Neurodegenerative Diseases, University Hospital, Bonn, University of Gottingen | Sep 2017 | Mar 2022 |
| XPro1595 | Inflammation | TNF inhibitor | Reduce neuroinflammation |
Recruiting |
Immune bio, Alzheimer's association | Nov 2019 | Dec 2020 |
Abbreviations: AAV, adeno‐associated virus; Aβ, amyloid beta; ADDF, Alzheimer's Drug Discovery Foundation; ApoE, apolipoprotein E; CADRO, Common Alzheimer's Disease and Related Disorders Research Ontology; CSF, cerebrospinal fluid; CSF‐1R, colony‐stimulating factor 1 receptor; DMT, disease‐modifying therapy; GABA, gamma‐aminobutyric acid; hTERT, human telomerase reverse transcriptase; NIA, National Institute on Aging; RIPK1, receptor‐interacting serine/threonine‐protein kinase 1; SGLT2, sodium glucose co‐transporter 2; SIGLEC‐3, sialic acid‐binding Ig‐like lectin 3; SNRI, serotonin‐norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TREM2, triggering receptor expressed on myeloid cells 2.
Note: Twenty‐seven agents in 27 Phase 1 clinical trials currently ongoing as of February 27, 2020 according to ClinicalTrials.gov.
Note: Bolded terms represent new agents into the 2020 Phase 1 pipeline since 2019.