TABLE 1.
Agents in Phase 3 Alzheimer's disease drug development (clinicaltrials.gov accessed January 1, 2024).
| Agent | Therapeutic purpose | CADRO target | Mechanism of action | Clinical trial | Lead sponsor | Start Date | Estimated primary completion date |
|---|---|---|---|---|---|---|---|
| ACP‐204 | Neuropsychiatric symptom | Neurotransmitter Receptors | Selective antagonist/inverse agonist of 5‐hydroxytryptamine (serotonin) receptor subtype 2A | NCT06159673 | ACADIA Pharmaceuticals Inc. | Nov 2023 | Jan 2028 |
| Aducanumab | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid monoclonal antibody directed at plaques and oligomers |
Biogen Biogen |
Mar 2020 Jun 2022 |
Aug 2023 Dec 2025 |
|
| AR1001 | Disease‐modifying small molecule | Neurotransmitter receptors | PDE5 inhibitor that reduces amyloid production and decreases inflammation in animal models of AD | NCT05531526 | AriBio Co., Ltd. | Dec 2022 | Dec 2025 |
| AVP‐786 | Neuropsychiatric symptom | Neurotransmitter receptors | NMDA receptor antagonist, sigma 1 receptor agonist; serotonin and norepinephrine transporter inhibitor |
Otsuka Pharmaceutical Development & Commercialization, Inc. |
Dec 2015 Oct 2017 Jul 2020 Sep 2020 |
Jul 2025 Dec 2023 Dec 2024 Dec 2024 |
|
| AXS‐05 | Neuropsychiatric symptom | Neurotransmitter receptors | NMDA receptor antagonist, sigma 1 receptor agonist; serotonin and norepinephrine transporter inhibitor | Axsome Therapeutics, Inc. |
Jun 2021 Sep 2022 |
Jun 2023 Jun 2025 |
|
| Blarcamesine | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | Sigma‐1 receptor agonist, M2 autoreceptor antagonist | NCT04314934 | Anavex Life Sciences Corp. | Oct 2019 | Jul 2024 |
| Buntanetap | Disease‐modifying small molecule | Proteostasis/proteinopathies | Decrease protein translation | NCT05686044 | Annovis Bio Inc. | Apr 2023 | Feb 2024 |
| Caffeine | Cognitive enhancement | Neurotransmitter receptors | Adenosine antagonist; non‐specific phosphodiesterase inhibitor | NCT04570085 | University Hospital, Lille | Mar 2021 | Nov 2024 |
| Donanemab | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid monoclonal antibody specific for pyroglutamate plaque amyloid |
Eli Lilly and Company |
Jun 2020 Aug 2021 Oct 2022 Feb 2023 |
Apr 2023 Oct 2027 Apr 2027 Mar 2024 |
|
| Donepezil | Cognitive enhancement | Neurotransmitter receptors | Acetylcholinesterase inhibitor; adipokine modulation |
Assistance Publique—Hôpitaux de Paris The University of Texas Health Science Center at San Antonio |
Feb 2022 Mar 2024 |
Aug 2026 Nov 2028 |
|
| E2814 | Disease‐modifying biologic | Tau | Anti‐tau monoclonal antibody |
Washington University School of Medicine |
Dec 2012 Dec 2021 |
Oct 2027 Jul 2027 |
|
| Escitalopram | Neuropsychiatric symptom | Neurotransmitter receptors | Selective serotonin reuptake inhibitor | NCT03108846 | JHSPH Center for Clinical Trials | Jan 2018 | May 2024 |
| Fosgonimeton | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | Hepatocyte growth factor (HGF); activates signaling via the hepatocyte growth factor (HGF)/MET receptor system; promotes survival of neurons, enhances hippocampal synaptic plasticity | Athira Pharma |
Sep 2020 Jun 2021 |
Jul 2024 Jan 2027 |
|
| Gantenerumab | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid monoclonal antibody | NCT01760005 | Washington University School of Medicine | Dec 2012 | Oct 2027 |
| GnRH | Disease‐modifying biologic | Growth factors and hormones | Anti‐aging | NCT04390646 | Nelly Pitteloud | Aug 2020 | Dec 2028 |
| Guanfacine | Cognitive enhancement | Neurotransmitter receptors | Alpha‐2 adrenergic agonist | NCT03116126 | Imperial College London | Jan 2019 | Dec 2022 |
| KarXT | Neuropsychiatric symptom | Neurotransmitter receptors | Muscarinic cholinergic agonist with peripheral anticholinergic |
Karuna Therapeutics |
Aug 2022 Jul 2023 Dec 2023 |
Mar 2025 Apr 2026 Jul 2025 |
|
| Lecanemab | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid monoclonal antibody directed at amyloid protofibrils and amyloid plaques |
Washington University School of Medicine Eisai Inc. Eisai Inc. Washington University School of Medicine |
Dec 2012 Mar 2019 Jul 2020 Dec 2021 |
Oct 2027 Sep 2027 Oct 2027 Jul 2027 |
|
| Levetiracetam | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | Modulator of the synaptic vesicle protein (SV2A) to reduce aberrant neuronal hyperactivity | NCT05986721 | AgeneBio | Dec 2024 | Jul 2028 |
| Masitinib | Disease‐modifying small molecule | Inflammation | Tyrosine kinase inhibitor; exhibits neuroprotection via inhibition of mast cell and microglia/macrophage activity | NCT05564169 | AB Science | Jan 2024 | Dec 2026 |
| Masupirdine | Neuropsychiatric symptom | Neurotransmitter receptors | 5HT6 receptor antagonist | NCT05397639 | Suven Life Sciences Limited | Nov 2022 | Jan 2025 |
| Metformin | Disease‐modifying small molecule | Metabolism and bioenergetics | Insulin sensitizer | NCT04098666 | Columbia University | Mar 2021 | Mar 2026 |
| Nabilone | Neuropsychiatric symptom | Neurotransmitter receptors | Synthetic cannabinoid; cannabinoid (receptor agent); antiemetic | NCT04516057 | Sunnybrook Health Sciences Center | Feb 2021 | Oct 2025 |
| Nilotinib BE | Disease‐modifying small molecule | Proteostasis/Proteinopathies | Abl tyrosine kinase inhibitor; autophagy enhancer | NCT05143528 | KeifeRx, LLC | Feb 2022 | Dec 2025 |
| Piromelatine | Disease‐modifying small molecule | Circadian rhythm | Melatonin and serotonin receptor agonist | NCT05267535 | Neurim Pharmaceuticals Ltd. | May 2022 | May 2024 |
| PM012 | Disease‐modifying small molecule | Neurogenesis | Upregulation of BDNF | NCT05811000 | Mediforum Ltd., Co. | Nov 2020 | Feb 2021 |
| Remternetug | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid monoclonal antibody | NCT05463731 | Eli Lilly and Company | Aug 2022 | Oct 2025 |
| Semaglutide | Disease‐modifying biologic | Inflammation | GLP‐1 agonist; anti‐inflammatory and insulin sensitivity effects |
Novo Nordisk A/S |
May 2021 May 2021 Jun 2023 |
Sep 2025 Sep 2025 May 2024 |
|
| Simufilam | Disease‐modifying small molecule | Synaptic plasticity/neuroprotection | Filamin A conformation stabilizer; disrupts the interaction of filamin A with the alpha 7 nicotinic acetylcholine receptor to reduce tau hyperphosphorylation and neurodegeneration; dependent on A‐beta's signaling via the alpha 7 pathway |
Cassava Sciences, Inc. |
Nov 2021 Nov 2021 Nov 2022 |
Oct 2024 May 2025 Jul 2026 |
|
| Solanezumab | Disease‐modifying biologic | Amyloid beta | Anti‐amyloid monoclonal antibody | NCT01760005 | Washington University School of Medicine | Dec 2012 | Oct 2027 |
| Tricaprilin | Cognitive enhancement | Metabolism and bioenergetics | Caprylic acid is metabolized to ketone bodies to create ketosis and stimulate mitochondria | NCT05809908 | Cerecin | Jan 2024 | Jan 2026 |
| Valiltramiprosate | Disease‐modifying small molecule | Amyloid beta | Prodrug of tramiprostate | NCT04770220 | Alzheon Inc. | May 2021 | May 2024 |