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. 2024 Apr 24;10(2):e12465. [Article in Dutch] doi: 10.1002/trc2.12465

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

NCT04241068

NCT05310071

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

NCT02446132

NCT03393520

NCT04408755

NCT04464564

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

NCT04947553

NCT05557409

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

NCT04437511

NCT05026866

NCT05508789

NCT05738486

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

NCT04661280

NCT05592678

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

NCT01760005

NCT05269394

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

NCT04488419

NCT04886063

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

NCT05511363

NCT05980949

NCT06126224

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

NCT01760005

NCT03887455

NCT04468659

NCT05269394

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

NCT04777396

NCT04777409

NCT05891496

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

NCT04994483

NCT05026177

NCT05575076

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