Alzheimer's disease drug development pipeline: 2026

Abstract

INTRODUCTION

Discovery and development of new therapies for Alzheimer's disease (AD) are urgently needed to address the world's growing population of individuals on the AD pathophysiological continuum. Clinicaltrials.gov is a resource for studying drugs in development for treatment of AD.

RESULTS

There are currently 158 drugs in 192 AD trials. Of the agents in trials, 39% are small molecule disease targeting therapies (DTTs); 34% are biologic DTTs; 18% are cognition enhancing symptom targeted therapies (STTs); and 10% are STTs being developed to treat neuropsychiatric symptoms of AD. Currently active trials require 54,728 participants of which 38,417 are in Phase 3. The biopharmaceutical industry sponsors 59% of AD trials including 72% of Phase 3 trials. Repurposed drugs represent 35% of the drugs in trials.

DISCUSSION

The AD drug development pipeline has a growing number of trials and drugs in trials. A diverse array of AD pathophysiological processes is being addressed by drugs in trials.

Highlights

• There are 158 drugs for the treatment of Alzheimer's disease in the 2026 drug development pipeline.

• Repurposed agents account for 35% of Alzheimer's disease drugs in development.

• 55,000 participants are required to populate all currently active trials.

• 73% of drugs in the pipeline are disease targeted therapies whose goal is to slow disease progression.

• The biopharmaceutical industry sponsors 59% of all trials and 72% of Phase 3 trials.

1. BACKGROUND

Alzheimer's disease (AD) Is the most common cause of cognitive impairment in later life and is projected to increase steadily with the aging of the population. Considering the continuum of AD from asymptomatic biomarker positive, to mild cognitive impairment (MCI) with evidence of AD pathology, to AD dementia, the number of affected individuals in the United States will increase from 46.7 million (biomarker positive, no symptoms), 2.43 million (MCI), and 3.65 million (AD dementia) in 2017 to 75.68 million (biomarker positive without symptoms), 5.7 million (MCI), and 9.3 million (AD dementia) in 2060. ¹ Although calculations, vary, studies suggest that, by 2060, approximately 90 million persons in the United States will have AD‐type changes in the brain with or without manifest symptoms of cognitive impairment.

There has been important progress in developing new disease targeted therapies (DTTs) for AD in the form of anti‐amyloid monoclonal antibodies (MABs) and success in development of symptom targeted therapies (STT) for the treatment of agitation associated with dementia due to AD. ² , ³ There are no DTTs approved for preclinical AD or for moderate to severe AD dementia; no new classes of cognition enhancing agents have been approved since 2004; and there are no treatments for non‐agitation neuropsychiatric symptoms (NPS) such of AD as psychosis, depression, or apathy. There is a great unmet need for DTT and STT drug development to address the needs of the growing population of individuals with AD.

We describe AD drug development as reflected in the clinical trials for AD related therapies registered on clinicaltrials.gov. We describe agents in Phase 1, 2, and 3 clinical trials for preclinical AD (biomarker changes without symptoms), MCI due to AD, and AD dementia. We note biomarkers included in the trial as reported on the federal registry. We sum the number of participants needed for all currently active trials. We discuss the global distribution of trial activity and describe trial sponsorship. Our goal is to provide information useful for trial planning, conduct, and analysis and to assist stakeholders in understanding the landscape of evolving AD therapeutics.

2. METHODS

Our methodologic approach builds on our previous AD pipeline studies. ⁴ , ⁵ The data reviewed for this report were collected from clinicaltrials.gov, a clinical trial registry maintained by the US National Library of Medicine of the National Institutes of Health (NIH). All clinical trials that have at least one site in the US, are conducted under a Food and Drug Administration (FDA) Investigational New Drug (IND) authorization, or involve a drug that is manufactured in the United States or its territories must be registered on clinicaltrials.gov within 21 days of enrolling the first participant.

For this report, data in clinicaltrials.gov are accessed in the application programming interface (API) of the registry and transferred to the database of the UNLV Clinical Trial Observatory and the Cleveland Clinic Laboratory of Network Medicine for analysis and interpretation.Raw data are retrieved from clinicaltrials.gov as they are posted, and the data (in Json format) are parsed according to the API's data structure to extract more than 30 key data fields. Automated filtering is performed combining rule‐based programming and manual curation by experts to identify and characterize trials testing AD pharmacological interventions. All extracted and annotated data are stored in a relational database using PostgreSQL for querying and analysis.

The Index Date for this review is January 1, 2026. Numbers, percentages, and other numerical data provided reflect clinical trials active on the Index Date. Trials reaching their completion date prior to the Index Date or initiated and registered after the Index Date are not included. We capture data on all active trials identified including those labeled as recruiting, active but not recruiting, enrolling by invitation (e.g., open‐label extensions of trials with enrollment limited to those participating in a previous trial of the same drug), and not yet recruiting (e.g., registered on clincaltrials.gov but no participants have been enrolled). Trials that are suspended, terminated, completed, withdrawn, or unknown (defined as having no status update within the past 2 years) are described in the report but not included among the active clinical trial summaries and calculations.

RESEARCH IN CONTEXT

1. Systematic review: Four mechanisms of action have been verified by therapeutic benefit in Alzheimer's disease (AD): cholinergic agents, an N‐methyl‐D‐aspartate agent, three anti‐amyloid monoclonal antibodies, and a multi‐transmitter antipsychotic for reduction of agitation. Agents that address other target processes and study of combination approaches are needed. The current AD drug development pipeline includes 192 clinical trials assessing 158 candidate therapies. There are 36 drugs in Phase 3, 84 potential treatments in Phase 2, and 45 agents in Phase 1. Disease targeting therapies (DTTs) account for 73% of agents in trial; cognition enhancing symptom targeted therapies (STTs) contribute 18% of agents in the pipeline; and drugs targeting neuropsychiatric symptoms account for 10% of drugs in active trials.

2. Interpretation: Most agents in trials are intended to prevent or delay the onset of AD or slow the progression of disease symptoms. A few agents in trials have the goal of improving memory and cognition or reducing behavioral changes occurring in patients with AD. The biopharmaceutical industry sponsors most trials, especially those of drugs in late‐stage development. Repurposing plays an important role in AD drug development and repurposed agents comprise almost half of Phase 2 drugs. The federal registry clinicaltrials.gov is a rich resource of information on drug development for AD.

3. Future directions: Review of the current drug development pipeline provides the basis for optimism regarding the emergence of new therapies for patients with AD. There are a robust number of trials, and agents in trials target a variety of pathophysiological disease processes. Biomarkers are increasingly used for participant identification and as pharmacodynamic outcomes. Progress is evident in clinical trial design, integration of biomarkers into trials, and emergence of promising candidate therapies.

We include trials in Phase 1, Phase 1/2, Phase 2, Phase 2/3, and Phase 3. When trials span two phases, we use the higher number for our calculations. We do not include Phase 0 or Phase 4 clinical trials in this report. We note novel agents in each phase; if an agent is being assessed in more than one phase, it is counted only once in totals of novel agents.

Our search terms include “Alzheimer's disease” and terms related to AD (e.g., dementia of the Alzheimer type, prodromal AD, preclinical AD, and MCI). We do not include trials whose participants have dementia of any cause or in which AD is included with other dementias. MCI as a manifestation of a non‐AD condition such as MCI of Parkinson's disease is excluded.

We capture comprehensive data regarding trials available on clinicaltrials.gov including the name of the test agent, trial title, national clinical trial (NCT) numerical identifier, actual start date, projected primary end date, whether a biomarker was required for eligibility or served as a primary or secondary outcome, and whether the agent was repurposed (e.g., approved for another indication or repositioned during development). To determine if a drug is repurposed (e.g., approved for a non‐AD indication), we compare the agents in the AD drug development pipeline to the available version of DrugBank (https://go.drugbank.com/).

We describe where the trials were performed (North America; non–North America with no North American sites; global, North American and non–North American sites included in the trial). We identify the “lead sponsors” of trials as industry or not industry. AD trials not funded by industry are funded by the National Institute on Aging (NIA), other federal agencies such as the Veterans Administration, non‐US governmental agencies, advocacy groups, or philanthropy.

We calculated the number of active trials sites in seven global regions. An “active” site was participating in at least one clinical trial on the Index Date.

We note if the trial population is cognitively normal with biomarker evidence of AD, has MCI/prodromal AD, or exhibits mild, moderate, or severe AD dementia. If other trial designations are used such as “early AD” (MCI plus mild AD dementia), we use the population as described in clinicaltrials.gov. Not all trials used biomarkers to determine participant eligibility.

We derive the target process of the agent in the trial based on the descriptive categories of the Common Alzheimer's Disease Research Ontology (CADRO). ⁶ CADRO categories include amyloid‐beta protein (Aß); tau; apolipoprotein E (APOE), lipids, and lipoprotein receptors; transmitter receptors; neurogenesis; inflammation and immune dysfunction; oxidative stress; cell death; proteostasis/proteinopathies; metabolism and bioenergetics; vascular factors; growth factors and hormones; synaptic plasticity/neuroprotection; gut–brain axis; circadian rhythm; environmental factors; epigenetic regulators; multitarget; unknown target; and “other”. Within each of these categories of target processes, agents can have one or several specific mechanisms of action (MoAs). The MoAs presented in Tables 1, 2, 3 are derived from clinicaltrials.gov or from review of the relevant literature and informational websites such as ALZFORUM.

TABLE 1.

Agents in Phase 3 Alzheimer's disease drug development (clinicaltrials.gov accessed January 1, 2026).

Agent	Therapeutic purpose	CADRO	Mechanism of action	Clinical trial	Lead sponsor	Start date	Primary completion date
ACP‐204	STT; neuropsychiatric (psychosis)	Neurotransmitter receptors	Selective antagonist/inverse agonist of 5‐hydroxytryptamine (serotonin) receptor subtype 2A	NCT06159673 NCT06194799	ACADIA Pharmaceuticals Inc. ACADIA Pharmaceuticals Inc.	Nov, 2023 Apr, 2024	Jan, 2028 Apr, 2029
AR1001	DTT; small molecule	Synaptic plasticity/ neuroprotection	Phosphodiesterase 5 (PDE‐5) inhibitor; improves synaptic plasticity	NCT05531526	AriBio Co., Ltd.	Dec, 2022	May, 2026
Buntanetap	DTT; small molecule	Proteostasis/ proteinopathies	Inhibits the translation of mRNA of amyloid precursor protein (APP), tau, α‐synuclein	NCT06709014	Annovis Bio Inc.	Feb, 2025	Dec, 2027
Caffeine	STT; cognition enhancer	Neurotransmitter receptors	Adenosine antagonist; non‐specific phosphodiesterase inhibitor	NCT04570085	University Hospital, Lille	Mar, 2021	Nov, 2026
Donanemab	DTT; biologic	Amyloid‐beta	Monoclonal antibody specific for pyroglutamate form of Aβ	NCT04437511 NCT05026866 NCT05508789 NCT05738486 NCT06996730	Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company Banner Health	Jun, 2020 Aug, 2021 Oct, 2022 Feb, 2023 Jan, 2026	Apr, 2023 Nov, 2027 May, 2028 May, 2024 Jun, 2030
Donepezil	STT; cognition enhancer	Neurotransmitter receptors	Cholinesterase inhibitor to raise synaptic levels of brain acetylcholine	NCT04661280	Assistance Publique—Hôpitaux de Paris	Feb, 2022	Aug, 2026
Escitalopram	STT; neuropsychiatric (agitation)	Neurotransmitter receptors	Selective serotonin reuptake inhibitor	NCT03108846	JHSPH Center for Clinical Trials	Jan, 2018	Apr, 2024
Etalanetug (E2814) + Lecanemab (BAN2401)	DTT; biologic	Multi‐target	Anti‐tau monoclonal antibody plus anti‐amyloid monoclonal antibody	NCT01760005 NCT05269394	Washington University School of Medicine Washington University School of Medicine	Dec, 2012 Dec, 2021	Apr, 2028 Apr, 2028
Gantenerumab	DTT; biologic	Amyloid‐beta	Monoclonal antibody directed at Aβ plaques and oligomers	NCT01760005	Washington University School of Medicine	Dec, 2012	Apr, 2028
Gonadorelin	DTT; biologic	Growth factors and hormones	Reduces luteinizing hormone by suppressing the hypothalamic‐pituitary‐gonadal axis with anticipated effects on protein aggregation and synaptic plasticity	NCT04390646	Nelly Pitteloud	Aug, 2020	Dec, 2028
Guanfacine	STT; cognition enhancer	Neurotransmitter receptors	Alpha‐2 adrenergic agonist to enhance noradrenergic function	NCT03116126	Imperial College London	Jan, 2019	Aug, 2024
Huperzine A	STT; cognition enhancer	Neurotransmitter receptors	Cholinesterase inhibitor to raise synaptic levels of brain acetylcholine	NCT07066826	Wanbangde Pharmaceutical Group Co., LTD	Aug, 2025	Aug, 2028
KarXT	STT; neuropsychiatric (psychosis)	Neurotransmitter receptors	Muscarinic cholinergic agonist plus a peripheral anticholinergic agent	NCT05511363 NCT05980949 NCT06126224 NCT06585787	Karuna Therapeutics Karuna Therapeutics Karuna Therapeutics Karuna Therapeutics	Aug, 2022 Jul, 2023 Aug, 2023 Sep, 2024	Oct, 2026 Sep, 2027 Jul, 2025 Sep, 2026
KarXT + KarX‐EC	STT; cognition enhancer STT; neuropsychiatric (agitation, psychosis)	Neurotransmitter receptors	Muscarinic cholinergic agonist plus a peripheral anticholinergic agent	NCT06937229 NCT06947941 NCT06976203 NCT06976216 NCT07011732 NCT07011745	Bristol‐Myers Squibb Bristol‐Myers Squibb Bristol‐Myers Squibb Bristol‐Myers Squibb Bristol‐Myers Squibb Bristol‐Myers Squibb	Dec, 2025 Jul, 2025 Jul, 2025 Jul, 2025 Jul, 2025 Jul, 2025	Jun, 2029 Sep, 2027 Sep, 2028 Sep, 2028 Nov, 2028 Nov, 2028
Latrepirdine	STT; cognition enhancer	Neurotransmitter receptors	H1 histamine blocker; modulator of multiple transmitters	NCT07251023	Bigespas LTD	Nov, 2025	May, 2027
Lecanemab	DTT; biologic	Amyloid‐beta	Anti‐amyloid monoclonal antibody directed at amyloid protofibrils and plaques	NCT01760005 NCT03887455 NCT04468659 NCT06384573	Washington University School of Medicine Eisai Inc. Eisai Inc. Washington University School of Medicine	Dec, 2012 Mar, 2019 Jul, 2020 Jun, 2024	Apr, 2028 Jun, 2029 Dec, 2028 Jun, 2030
Levetiracetam	STT; other symptoms (seizure)	Neurotransmitter receptors	SV2A modulator; improves synaptic function; reduces Aβ‐induced neuronal hyperactivity	NCT07234695	Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau	Nov, 2025	Dec, 2027
Masitinib	DTT; small molecule	Inflammation	Tyrosine kinase inhibitor to activate lyn/fyn and reduce activation of microglial cells	NCT05564169	AB Science	Jun, 2026	Dec, 2028
Masupirdine	STT; neuropsychiatric (agitation)	Neurotransmitter receptors	5‐HT6 antagonist; modulate release of acetylcholine and glutamate	NCT05397639	Suven Life Sciences Limited	Nov, 2022	Dec, 2025
Metformin	DTT; small molecule	Metabolism and bioenergetics	Insulin sensitizer to improve brain glucose metabolism	NCT04098666	Columbia University	Mar, 2021	Apr, 2026
MLC901	DTT; small molecule	Multi‐target	Natural product consisting of several herbs; modulation of Aβ and tau phosphorylation, reduction of oxidative stress and inflammation, and promotion of neurogenesis and synaptogenesis	NCT07191028	Moleac Pte Ltd.	Dec, 2025	Jun, 2028
Nabilone	STT; neuropsychiatric (agitation)	Neurotransmitter receptors	Synthetic cannabinoid agonist; modulates the endocannabinoid system	NCT04516057	Sunnybrook Health Sciences Centre	Feb, 2021	Oct, 2025
Nilotinib	DTT; small molecule	Proteostasis/proteinopathies	Tyrosine kinase inhibitor; autophagy enhancer; promotes clearance of Aβ and tau	NCT05143528	KeifeRx, LLC	Feb, 2022	Dec, 2025
Piromelatine	STT; cognition enhancer	Neurotransmitter receptors	Melatonin receptor agonist; 5‐HT 1A and 1D serotonin receptor agonist	NCT05267535	Neurim Pharmaceuticals Ltd.	May, 2022	Jun, 2025
Remternetug	DTT; biologic	Amyloid‐beta	Anti‐amyloid monoclonal antibody targeting the pyroglutamate form of Aβ	NCT05463731 NCT05552157 NCT06647498 NCT06653153	Eli Lilly and Company Washington University School of Medicine Washington University School of Medicine Eli Lilly and Company	Aug, 2022 Nov, 2024 Nov, 2024 Oct, 2024	Apr, 2024 Mar, 2034 Mar, 2034 Apr, 2029
RG6289	DTT; small molecule	Amyloid‐beta	Gamma secretase modulator altering gamma secretase interaction with amyloid precursor protein	NCT06996730	Banner Health	Jan, 2026	Jun, 2030
RG6289 + donanemab	DTT; biologic	Amyloid‐beta	Gamma secretase modulator altering gamma secretase interaction with amyloid precursor protein + anti‐amyloid monoclonal antibody	NCT06996730	Banner Health	Jan, 2026	Jun, 2030
Rotigotine + rivastigmine	STT; cognition enhancer	Neurotransmitter receptors	Combined dopamine agonist and cholinesterase inhibitor	NCT06702124	I.R.C.C.S. Fondazione Santa Lucia	Dec, 2023	Jul, 2025
Semaglutide	DTT; biologic	Inflammation	GLP‐1 agonist; reduces neuroinflammation and improves insulin signaling in the brain	NCT04777396 NCT04777409 NCT05891496	Novo Nordisk A/S Novo Nordisk A/S Novo Nordisk A/S	May, 2021 May, 2021 Jun, 2023	Sep, 2025 Sep, 2025 Aug, 2024
Solanezumab	DTT; biologic	Amyloid‐beta	Monoclonal antibody directed at Aβ monomers	NCT01760005	Washington University School of Medicine	Dec, 2012	Apr, 2028
T3D‐959	DTT; small molecule	Metabolism and bioenergetics	Dual agonist of PPARδ/γ targeting reduced glucose and altered lipid metabolism	NCT06964230	T3D Therapeutics, Inc.	Oct, 2026	Apr, 2031
Tertomotide	DTT; biologic	Amyloid‐beta	hTERT peptide vaccine; mimics extra‐telomeric functions to inhibit neurotoxicity, apoptosis, and reactive oxygen species	NCT05303701	Samsung Pharmaceutical Co., Ltd.	May, 2025	Dec, 2027
Tricaprilin	STT; cognition enhancer	Metabolism and bioenergetics	Caprylic triglyceride; induces ketosis and improves mitochondrial and neuronal function	NCT05809908	Cerecin	Jun, 2026	Dec, 2028
Trontinemab	DTT; biologic	Amyloid‐beta	Anti‐amyloid monoclonal antibody with Brainshuttle® utilizing transferrin receptor to enhance blood brain barrier penetration	NCT07169578 NCT07170150	Hoffmann‐La Roche Hoffmann‐La Roche	Sep, 2025 Nov, 2025	Jun, 2028 Jun, 2028
Valiltramiprosate	DTT; small molecule	Amyloid‐beta	Prodrug of tramiprosate; inhibits Aβ aggregation into toxic oligomers	NCT06304883	Alzheon Inc.	Apr, 2024	Dec, 2026
Wujia Yizhi	DTT; small molecule	Multi‐target	Herbal mixture with effects on inflammation, apoptosis, calcium signaling	NCT06534723	Sichuan Jishengtang Pharmaceutical Co., Ltd.	Aug, 2024	Aug, 2026

Abbreviations: Aß, amyloid‐beta protein; CADRO, Common Alzheimer's Disease Research Ontology; DTT, disease targeted therapy; GLP‐1, glucagon‐like peptide‐1; STT, symptom targeted therapy.

TABLE 2.

Agents in Phase 2 Alzheimer's disease drug development (clinicaltrials.gov accessed January 1, 2026).

Agent	Therapeutic purpose	CADRO	Mechanism of action	Clinical trial	Lead sponsor	Start date	Primary completion date
2‐HOBA	DTT; small molecule	Oxidative stress	Scavenger for reactive carbonyl species to decreased oxidative neuronal injury	NCT06432166	MTI Biotech Inc	Sep, 2025	Jun, 2028
AADvac1	DTT; biologic	Tau	Active immunotherapy against tau protein	NCT07167966	Paul S. Aisen	Nov, 2025	Aug, 2028
AADvac1 + AAmAb	DTT; biologic	Multi‐target	Tau vaccine + anti‐ Aβ monoclonal antibody	NCT07167966	Paul S. Aisen	Nov, 2025	Aug, 2028
ACI‐24.060	DTT; biologic	Amyloid‐beta	Vaccine against Aβ	NCT05462106	AC Immune SA	Jun, 2022	Jun, 2026
AL101	DTT; biologic	Inflammation	MAB directed at the sortilin receptor to decrease lysosomal degradation of progranulin and enhance progranulin function as an immune regulator	NCT06079190 NCT07105709	GlaxoSmithKline GlaxoSmithKline	Oct, 2023 Aug, 2025	Sep, 2026 Sep, 2028
Aldesleukin	DTT; biologic	Inflammation	Binds with IL‐2 receptor to activate intermediates and reduce cytokine production	NCT05468073 NCT06096090	Centre Hospitalier St Anne The Methodist Hospital Research Institute	Oct, 2022 Jan, 2022	Sep, 2025 Dec, 2025
Aluminum hydroxide	DTT; small molecule	Inflammation	Activates immune pathways to improve the immune response	NCT07107074	ADvantage Therapeutics	Nov, 2023	Dec, 2026
ARO‐MAPT	DTT; biologic	Tau	RNA interference to silence the MAPT tau gene	NCT07221344	Arrowhead Pharmaceuticals	Nov, 2025	Jun, 2027
Astragalus	STT; cognition enhancer	Multi‐target	Traditional Chinese medicine	NCT05578443 NCT05647473	Fujian Medical University Union Hospital Fujian Medical University Union Hospital	May, 2024 Feb, 2024	Jul, 2025 May, 2025
Baricitinib	DTT; small molecule	Inflammation	Janus kinase inhibitor to reduce inflammatory cytokine signaling	NCT05189106	Massachusetts General Hospital	Dec, 2022	Feb, 2025
Benfotiamine	DTT; small molecule	Metabolism and bioenergetics	Synthetic thiamine to improve neuronal metabolism and function	NCT06223360	Alzheimer's Disease Cooperative Study (ADCS)	Mar, 2024	Dec, 2027
BEY2153	DTT; small molecule	Proteostasis/proteinopathies	Aβ and tau aggregation inhibitor; inhibits neuronal death	NCT06885567	BeyondBio Inc.	Jul, 2025	Jul, 2028
BIIB080	DTT; biologic	Tau	Antisense oligonucleotide blocking tau mRNA translation	NCT05399888	Biogen	Aug, 2022	May, 2026
BMS‐986368	STT; neuropsychiatric (agitation)	Neurotransmitter receptors	Inhibits fatty acid amide hydrolase and monoacylglycerol lipase to modulate the endocannabinoid system	NCT06808984	Celgene	Jun, 2025	Jul, 2027
BMS‐986446	DTT; biologic	Tau	Anti‐tau monoclonal antibody targeting reduction of tau spread; directed at epitopes of the microtubule binding region	NCT06268886	Bristol‐Myers Squibb	Mar, 2024	Mar, 2027
Brexanolone	DTT; small molecule	Neurogenesis	Allosteric modulator of GABA‐A receptors	NCT04838301	University of Arizona	Aug, 2023	Mar, 2026
Brivaracetam	STT; cognition enhancer	Neurotransmitter receptors	Anticonvulsant with high affinity for synaptic vesicle protein 2A	NCT05899764	University of California, Los Angeles	Jan, 2025	Jun, 2029
Bumetanide	DTT; small molecule	APOE, lipids and lipoprotein receptors	Reverses APOE4‐specific Alzheimer's transcriptomic signatures	NCT06052163	Stanford University	Apr, 2023	Apr, 2025
Cannabidiol	STT; cognition enhancer STT; neuropsychiatric (agitation)	Neurotransmitter receptors	Endocannabinoid receptor agonist	NCT05822362 NCT06014424	University of Colorado, Denver Sunnybrook Health Sciences Centre	Jan, 2024 Sep, 2023	Apr, 2028 Dec, 2026
Ciprofloxacin + Celecoxib	DTT; small molecule	Inflammation	Celecoxib is a COX‐2 inhibitor that blocks prostaglandin synthesis to reduce an immune response	NCT06185543	NeuroSense Therapeutics Ltd.	Nov, 2023	Nov, 2025
Contraloid acetate	DTT; small molecule	Amyloid‐beta	Aggregation inhibitor	NCT06182085	PRInnovation GmbH	Dec, 2023	Apr, 2026
CORT108297	STT; cognition enhancer	Growth factors and hormones	Selective glucocorticoid receptor antagonist; reduces neuroendocrine stress responses	NCT04601038	Johns Hopkins University	Jun, 2021	Jun, 2026
DAOIB + AO	STT; cognition enhancer	Multi‐target	NMDA enhancement (DAOIB) + antioxidant (AO)	NCT06467539	Chang Gung Memorial Hospital	Jun, 2024	May, 2027
Daridorexant	DTT; small molecule	Circadian rhythm	Dual orexin antagonist for both orexin 1 and orexin 2 receptors	NCT07213349	Douglas Mental Health University Institute	Oct, 2025	Dec, 2028
Dasatinib + Quercetin	DTT; small molecule	Inflammation	Tyrosine kinase inhibitor (dasitinib); reduces T‐cell signaling and production of proinflammatory cytokines	NCT04685590 NCT04785300	Washington University School of Medicine Mayo Clinic	Dec, 2021 Jul, 2022	Jan, 2028 Jun, 2026
Dexmedetomidine	STT; neuropsychiatric (agitation)	Neurotransmitter receptors	Selective α2‐adrenergic receptor agonist to enhance noradrenergic function	NCT06052254	Teikoku Pharma USA, Inc.	Sep, 2025	Jan, 2027
Dimethyl fumarate	DTT; small molecule	Inflammation	Activates Nrf2 with reduction of NF‐kB signaling, inhibits NLRP3 inflammasome activation, reduces microglial activation and cytokine production	NCT06850597	Medical University of Lodz	Oct, 2024	Dec, 2027
Edaravone	DTT; small molecule	Oxidative stress	Free radical scavenger	NCT07252440	Shanghai Auzone Biological Technology Co., Ltd.	Dec, 2025	Oct, 2028
Emestedastat	STT; cognition enhancer	Growth factors and hormones	11‐β‐hydroxysteroid dehydrogenase type 1 inhibitor	NCT06125951	Actinogen Medical	Apr, 2024	Oct, 2026
Enrupatinib	DTT; small molecule	Inflammation	Colony stimulating factor 1 receptor (CSF‐1R) inhibitor to reduce microglial activation	NCT06745583	Elixiron Immunotherapeutics (Hong Kong) Ltd.	Dec, 2024	Mar, 2026
Etalanetug (E2814) + Lecanemab (BAN2401)	DTT; biologic	Multi‐target	Anti‐tau monoclonal antibody plus anti‐amyloid monoclonal antibody	NCT06602258	Eisai Inc.	Sep, 2024	Dec, 2026
EX039	DTT; small molecule	Synaptic plasticity/neuroprotection	Inhibits D‐amino acids oxidate to increase N‐methyl‐D‐aspartate receptor activity	NCT05413655	Excelsior	Aug, 2022	Dec, 2026
Exercised plasma	DTT; biologic	Synaptic plasticity/neuroprotection	Plasma transfusion from exercise‐trained donors to reduce toxic plasma elements and enhance synaptic function	NCT05068830	Norwegian University of Science and Technology	Sep, 2021	Sep, 2025
Fasudil	DTT; small molecule	Vasculature	Vasodilator to improve cerebral blood flow	NCT06362707	Helse Stavanger HF	Aug, 2024	Oct, 2025
Foralumab	DTT; biologic	Inflammation	Anti‐CD3 antibody that reduces effector T‐cells and microglial activation	NCT06489548	Brigham and Women's Hospital	Apr, 2025	Jun, 2026
IGC‐AD1	STT; neuropsychiatric (agitation)	Neurotransmitter receptors	Tetrahydrocannabinol binds to the CB1 receptor	NCT05543681	IGC Pharma, LLC	Oct, 2022	Mar, 2026
ITI‐1284	STT; neuropsychiatric (psychosis, agitation)	Neurotransmitter receptors	A deuterated form of lumateperone; 5‐HT2A receptor antagonist, D1 receptor modulator, D2 receptor modulator	NCT06540833 NCT06651567	Intra‐Cellular Therapies, Inc. Intra‐Cellular Therapies, Inc.	Aug, 2024 Oct, 2024	Sep, 2027 Oct, 2027
IVL3003	STT; cognition enhancer	Neurotransmitter receptors	Cholinesterase inhibitor to enhance acetylcholine and facilitate synaptic function	NCT05345509	Inventage Lab., Inc.	Apr, 2023	Nov, 2025
JNJ‐64042056	DTT; biologic	Tau	Active immunotherapy targeting tau protein	NCT06544616	Janssen Pharmaceutica N.V., Belgium	Jul, 2024	Jul, 2031
KarXT + KarX‐EC + Lecanemab	STT; cognition enhancer	Neurotransmitter receptors	Muscarinic cholinergic agonist plus a peripheral anticholinergic agent and an anti‐amyloid monoclonal antibody (lecanemab)	NCT07212062	Neurology Office of South Florida	Dec, 2025	Apr, 2028
Lemborexant	DTT; small molecule	Neurotransmitter receptors	Dual antagonist of orexin OX1 and OX2 receptors	NCT06274528	Washington University School of Medicine	Mar, 2024	Mar, 2029
Lenalidomide	DTT; small molecule	Inflammation	Multimodal immunomodulator that decreases inflammatory cytokines, increases anti‐inflammatory cytokines, and reduces microglial activation	NCT06177028	St. Joseph's Hospital and Medical Center, Phoenix	Jun, 2025	Jan, 2026
Leuprolide	DTT; small molecule	Growth factors and hormones	Gonadotropin growth hormone receptor agonist; lowers luteinizing hormone levels to reduce amyloid deposition and neurodegeneration	NCT03649724	Weill Medical College of Cornell University	Nov, 2020	Jul, 2026
Levetiracetam	DTT; small molecule	Synaptic plasticity/neuroprotection	SV2A modulator; improves synaptic function; reduces Aβ‐induced neuronal hyperactivity	NCT03875638	Beth Israel Deaconess Medical Center	Aug, 2019	Oct, 2025
LHP588	DTT; small molecule	Multi‐target	Inhibits gingipains leading to reduced inflammation, amyloid plaques, and tau pathology	NCT06847321	Lighthouse Pharmaceuticals, Inc.	Feb, 2025	Sep, 2028
Losartan + Amlodipine	DTT; small molecule	Vasculature	Angiotensin II receptor blocker (losartan), calcium channel blocker (amlodipine)	NCT05331144	Rong Zhang	Oct, 2022	Jun, 2027
Memantine	DTT; small molecule	Neurotransmitter receptors	NMDA receptor antagonist with neuroprotective effects	NCT05063851	University of Virginia	Oct, 2021	Dec, 2025
Methylphenidate + iTBS	STT; neuropsychiatric (apathy)	Neurotransmitter receptors	Norepinephrine and dopamine reuptake inhibitor; primes intermittent theta burst stimulation	NCT07279740	Sunnybrook Health Sciences Centre	Jan, 2026	Oct, 2027
Mevidalen	STT; cognition enhancer	Neurotransmitter receptors	Dopamine D1 receptor positive allosteric modulator	NCT06538116	Eli Lilly and Company	Aug, 2024	May, 2026
MIB‐626	DTT; small molecule	Amyloid‐beta	Decreases oxidative stress to improve mitochondrial function and enhance autophagy leading to decreased amyloid‐beta plaques	NCT05040321	Brigham and Women's Hospital	Dec, 2021	Oct, 2025
MK‐1167	STT; cognition enhancer	Undisclosed	Undisclosed	NCT06721156	Merck Sharp & Dohme LLC	Dec, 2024	Dec, 2026
MK‐2214	DTT; biologic	Tau	Anti‐tau monoclonal antibody	NCT07033494	Merck Sharp & Dohme LLC	Jul, 2025	Apr, 2029
ML‐007C‐MA	STT; neuropsychiatric (psychosis)	Neurotransmitter receptors	M1/M4 muscarinic agonist	NCT06887192	MapLight Therapeutics	Aug, 2025	Feb, 2027
Nicotinic Acid	DTT; small molecule	Inflammation	Engages the hydroxycarboxylic acid receptor 2 (HCAR2) on microglia to reduce plaque burden and neuronal dystrophy	NCT06582706	Indiana University	Dec, 2024	Feb, 2026
NSC001	STT; cognition enhancer	Neurotransmitter receptors	Orthosteric selective M1 cholinergic receptor agonist	NCT06995573	NSC‐Therapeutics	Jun, 2025	Jul, 2026
NSC001 + Trospium	STT; cognition enhancer	Neurotransmitter receptors	Orthosteric selective M1 cholinergic receptor agonist plus a repurposed anticholinergic agent to reduce peripheral cholinergic side effects	NCT06995573	NSC‐Therapeutics	Jun, 2025	Jul, 2026
NTRX‐07	DTT; small molecule	Neurotransmitter receptors	Cannabinoid type 2 receptor agonist; reduces microglial‐mediated inflammation	NCT07058688	NeuroTherapia, Inc.	Mar, 2025	Dec, 2025
ONO‐2020	STT; cognition enhancer STT; neuropsychiatric (agitation)	Epigenetic regulators	Epigenetic regulator modulating immune function and inflammation	NCT06803823 NCT06881836	Ono Pharmaceutical Co. Ltd Ono Pharmaceutical Co. Ltd	May, 2025 Apr, 2025	Dec, 2026 Jul, 2026
Ozanimod	DTT; small molecule	Inflammation	Sphingosine ‐1‐phospaste receptor modulator that reduces lymphocyte migration into the brain, decreasing microglial activation and proinflammatory cytokine release	NCT06862960	ChenXiaoChun	Jul, 2025	Jun, 2027
Parthenolide + Ipriflavone	DTT; small molecule	Multi‐target	Targets microbial‐mediated neuroinflammation and oxidation; reduces aggregation of Aβ protein; down regulates tau protein production; acetylcholinesterase inhibitor	NCT07236190	Massachusetts General Hospital	Dec, 2025	Jun, 2027
Polypill	STT; cognition enhancer	Undisclosed	Undisclosed	NCT06597058	Noah Pharmaceuticals, Inc.	Oct, 2024	Dec, 2025
Posdinemab	DTT; biologic	Tau	Monoclonal antibody targeting soluble tau protein	NCT04619420	Janssen Research & Development, LLC	Jan, 2021	Oct, 2025
Rifaximin	DTT; small molecule	Gut‐brain axis	Antibiotic to change microbiome composition	NCT06718686	Jasmohan Bajaj	Dec, 2024	Dec, 2025
RO7269162	DTT; small molecule	Amyloid‐beta	Gamma‐secretase modulator to reduce Aß production	NCT06402838	Hoffmann‐La Roche	May, 2024	Nov, 2026
RQC	DTT; small molecule	Amyloid‐beta	Reduces production and aggregation of Aß	NCT06470061	Zaparackas and Knepper LTD	Jul, 2024	Jul, 2027
Sabirnetug	DTT; biologic	Amyloid‐beta	Monoclonal antibody targeting soluble Aβ	NCT06335173	Acumen Pharmaceuticals	Feb, 2024	Oct, 2026
Sargramostim	DTT; biologic	Inflammation	Granulocyte macrophage colony stimulating factor that shifts microglia toward a phagocytic phenotype to remove amyloid protein	NCT04902703	University of Colorado, Denver	Jun, 2022	Nov, 2026
Semaglutide	DTT; biologic	Inflammation	GLP‐1 receptor agonist; reduces neuroinflammation and improves insulin signaling in the brain	NCT07135245 NCT07200622	Rune Skovgaard Rasmussen Imperial College London	Jan, 2026 Sep, 2025	Sep, 2030 Dec, 2027
Semaglutide + Candesartan + Vitamin D + Calcium	DTT; biologic	Inflammation	GLP‐1 receptor agonist; (reduces neuroinflammation and improves insulin signaling in the brain); angiotensin receptor blocker; calcium; vitamin D	NCT07135245	Rune Skovgaard Rasmussen	Jan, 2026	Sep, 2030
Senicapoc	DTT; small molecule	Inflammation	Calcium‐activated potassium channel blocker to inhibit activation of microglial and decrease proinflammatory cytokine release	NCT04804241	University of California, Davis	Mar, 2022	Dec, 2025
SHR‐1707	DTT; biologic	Amyloid‐beta	Anti‐amyloid monoclonal antibody	NCT06199037	Shanghai Hengrui Pharmaceutical Co., Ltd.	Feb, 2024	Apr, 2025
Siponimod	DTT; small molecule	Inflammation	Immunomodulation; Sphingosine ‐1‐phosphate receptor modulator to decrease microglial activation and proinflammatory cytokine release	NCT06639282	St. Joseph's Hospital and Medical Center, Phoenix	Jul, 2025	Oct, 2029
Sirolimus	DTT; small molecule	Vasculature	Enhances cerebral blood flow; mammalian target of rapamycin (mTOR) inhibitor with immunosuppressive effects	NCT04629495	The University of Texas Health Science Center at San Antonio	Aug, 2021	Mar, 2026
Sodium pentaborate pentahydrate	DTT; small molecule	Multi‐target	Affects dysregulated genes of multiple biological processes, including inflammation, cell stress, cell growth, cell proliferation, and apoptosis.	NCT06840054	Tabriz University of Medical Sciences	May, 2025	Jan, 2026
SPG302	DTT; small molecule	Synaptic plasticity/neuroprotection	Targets fascin to stimulate neurons to rebuild dendritic spines	NCT06427668	Spinogenix	Jul, 2024	Dec, 2025
Suvorexant	DTT; small molecule	Neurotransmitter receptors	Dual orexin receptor antagonist; improves sleep with effects on clearance of CSF Aβ and tau	NCT04629547	Washington University School of Medicine	May, 2022	May, 2026
Tadalafil	STT; cognition enhancer	Neurotransmitter receptors	Phosphodiesterase 5 (PDE5) inhibitor; elevates cyclic guanosine monophosphate (GMP) to improve neuroplasticity	NCT07172815	Imperial College London	Sep, 2025	Aug, 2028
Tisolagiline	STT; cognition enhancer	Neurotransmitter receptors	Monoamine oxidase inhibitor; increases dopamine availability; may reduce inflammation and neurodegeneration	NCT07027072	NeuroBiogen Co., Ltd	Aug, 2025	Jun, 2027
Trazodone	STT; cognition enhancer	Circadian rhythm	Serotonin reuptake inhibitor to restore sleep	NCT05282550	Johns Hopkins University	Feb, 2023	Jul, 2027
Trontinemab	DTT; biologic	Amyloid‐beta	Anti‐amyloid monoclonal antibody with Brainshuttle® utilizing transferrin receptor to enhance blood brain barrier penetration	NCT04639050	Hoffmann‐La Roche	Mar, 2021	Jun, 2030
VHB937	DTT; biologic	Inflammation	TREM2 antibody agonist that increases phagocytic activity of microglia	NCT07094516	Novartis Pharmaceuticals	Aug, 2025	Sep, 2028
VY7523	DTT; biologic	Tau	Recombinant humanized immunoglobulin gamma 4 (IgG4) monoclonal antibody targeting human pathological tau	NCT06874621	Voyager Therapeutics	Mar, 2025	May, 2027
XPro1595	DTT; biologic	Inflammation	TNF neutralizer to reduce interaction with TNF receptors that activate a pro‐inflammatory cascade	NCT05522387	Inmune Bio, Inc.	Feb, 2023	Jun, 2024
Zervimesine (CT1812)	DTT; small molecule	Synaptic plasticity/neuroprotection	Sigma‐2 receptor antagonist; competes with oligomeric Aβ binding; protects against Aβ‐induced synaptic toxicity	NCT05531656	Cognition Therapeutics	Jun, 2023	Apr, 2027

Abbreviations: Aß, amyloid‐beta protein; DTT, disease targeted therapy; GABA, gamma‐aminobutyric acid; GLP‐1, glucagon‐like peptide‐1; MAB, monoclonal antibody; STT, symptom targeted therapy; TNF, tumor necrosis factor.

TABLE 3.

Agents in Phase 1 Alzheimer's disease drug development (clinicaltrials.gov accessed January 1, 2026).

Agent	Therapeutic purpose	CADRO	Mechanism of action	Clinical trial	Lead sponsor	Start date	Primary completion date
AAV2‐BDNF	DTT; biologic	Growth factors and hormones	Genetically engineered AAV‐2 that expresses the human BDNF cDNA maintain neurons	NCT05040217	Mark Tuszynski	Feb, 2022	Dec, 2027
ADEL‐Y01	DTT; biologic	Tau	Monoclonal antibody targeting tau tubulin to decrease tau aggregation and propagation and enhance microglial tau clearance	NCT06247345	Alzheimer's Disease Expert Lab (ADEL), Inc.	Feb, 2024	Jun, 2027
AK152	DTT; biologic	Amyloid‐beta	Bispecific antibody targeting amyloid‐beta protein and the receptor‐mediated transcytosis mechanism of the blood brain barrier to enhance brain penetration	NCT07301502	Akeso	Dec, 2025	Jun, 2027
ALN‐5288	DTT; biologic	Tau	RNAi therapeutic targeting microtubule‐associated protein tau (MAPT)	NCT07214727	Alnylam Pharmaceuticals	Oct, 2025	Mar, 2030
AS‐S603	DTT; small molecule	Proteostasis/proteinopathies	Targets and dissolves Aβ and tau aggregates	NCT06786676	Amyloid Solution Inc	May, 2025	Apr, 2026
AV‐1959D	DTT; biologic	Amyloid‐beta	Anti‐amyloid vaccine	NCT05642429	Institute for Molecular Medicine	Feb, 2023	Feb, 2026
AV‐1959R	DTT; biologic	Amyloid‐beta	N‐terminal amyloid‐targeted vaccine (Aβ 1‐11)	NCT06831812	Nuravax, Inc.	Jun, 2024	Oct, 2025
AV‐1980R	DTT; biologic	Tau	Vaccine against tau protein epitope	NCT07158905	Institute for Molecular Medicine	Dec, 2025	Jun, 2029
BCG vaccine	DTT; biologic	Inflammation	Immunomodulation by enhancing systemic immunity	NCT06078891	Tamir Ben‐Hur	Jul, 2023	Dec, 2025
BIIB080	DTT; biologic	Tau	Antisense oligonucleotide blocking tau mRNA translation	NCT06454721	Biogen	Jan, 2025	Feb, 2026
BnH‐015B	STT; Cognition enhancer	Neurotransmitter receptors	Modulates GluN2B binding of NMDA receptors; regulates BDNF/TRKβ and microglial‐mediated IL‐33‐OPN signaling	NCT06535308	BnH Research	Oct, 2024	Apr, 2026
Cannabidiol	STT; neuropsychiatric (agitation)	Neurotransmitter receptors	Endocannabinoid receptor agonist	NCT04075435	Mclean Hospital	Jan, 2021	Jan, 2026
Centella asiatica	DTT; small molecule	Synaptic plasticity/neuroprotection	Antioxidant and anti‐inflammatory agent targeting synaptic and neuroprotective effects	NCT05591027	Oregon Health and Science University	Dec, 2022	Nov, 2025
Choline	DTT; small molecule	Metabolism and bioenergetics	Stabilizes lipid metabolism and restores cell function by increasing phosphatidylcholine activity	NCT05880849	Paul E Schulz	Jun, 2023	Nov, 2025
CM383	DTT; biologic	Amyloid‐beta	Anti‐amyloid monoclonal antibody	NCT06412185 NCT06619613	Keymed Biosciences Co.Ltd Keymed Biosciences Co.Ltd	May, 2024 Nov, 2024	Jun, 2025 Dec, 2026
CpG1018	DTT; biologic	Inflammation	Toll‐like receptor agonist that increases phagocytosis by microglia	NCT05606341	NYU Langone Health	Mar, 2023	Nov, 2025
DDN‐A‐0101	DTT; small molecule	Amyloid‐beta	Plaque reduction to decrease neuroinflammation and preserve synaptic function	NCT06367426	Pharmacobio	Apr, 2024	May, 2025
DUVAX	DTT; biologic	Inflammation	Reduces inflammation by preventing amyloid and tau protein aggregation	NCT07142278	Nuravax, Inc.	Nov, 2025	Apr, 2027
Emtricitabine	DTT; small molecule	Inflammation	Nucleoside reverse transcriptase inhibitor that reduces activity of LINE‐1 retrotransposons and inhibits the NLRP3 inflammasome	NCT04500847 NCT07210528	Butler Hospital National University Hospital, Singapore	Dec, 2021 Jun, 2025	Mar, 2026 Mar, 2026
Emtricitabine + Tenofovir alafenamide	DTT; small molecule	Inflammation	Nucleoside reverse transcriptase inhibitors that reduce activity of LINE‐1 retrotransposons and inhibits the NLRP3 inflammasome	NCT07210528	National University Hospital, Singapore	Jun, 2025	Mar, 2026
HHT201	STT; cognition enhancer	Neurotransmitter receptors	Cholinesterase inhibitor	NCT06373094	Shanghai Synergy Pharmaceutical Sciences Co., Ltd.	Jun, 2024	Mar, 2025
ION269	DTT; biologic	Amyloid‐beta	Antisense oligonucleotide directed at amyloid precursor protein	NCT06673069	Ionis Pharmaceuticals, Inc.	Dec, 2024	Feb, 2027
J4	DTT; small molecule	Synaptic plasticity/neuroprotection	Regulates neuronal excitability by modulating synaptic transmission	NCT06938763	Academia Sinica, Taiwan	Feb, 2025	Dec, 2026
KS101	DTT; small molecule	Metabolism and bioenergetics	Restores Klotho levels to improve cell metabolism decreasing oxidative damage, inflammation, and neurodegeneration	NCT07143331	Klotho Sciences Australia Pty Ltd.	Aug, 2025	Apr, 2026
Leucettinib‐21	DTT; small molecule	Tau	Antagonizes activity of the protein (DYRK1A protein kinase) derived from the DYRK1A gene to decrease tau hyperphosphorylation	NCT06206824	Perha Pharmaceuticals	Jan, 2024	Jun, 2026
LX1001	DTT; biologic	Epigenetic regulators	AAV gene transfer vector expressing the cDNA coding for human APOE2 directly to the CNS/CSF of APOE4 homozygotes with AD	NCT05400330	Lexeo Therapeutics	May, 2023	Nov, 2028
LY03017	STT; neuropsychiatric (psychosis, hallucination, delusion)	Neurotransmitter receptors	5‐HT2A receptor inverse agonist and 5‐HT2C receptor antagonist	NCT06388551 NCT06793995 NCT06980207	Luye Pharma Group Ltd. Luye Pharma Group Ltd. Luye Pharma Group Ltd.	May, 2024 Feb, 2025 May, 2025	Mar, 2025 Oct, 2025 Oct, 2025
LY3954068	DTT; biologic	Undisclosed	Undisclosed	NCT06297590	Eli Lilly and Company	Aug, 2024	Feb, 2027
LY4006895	DTT; biologic	Undisclosed	Undisclosed	NCT06657768	Eli Lilly and Company	Oct, 2024	Jul, 2027
MIB‐626	DTT; small molecule	Oxidative stress	Decreases oxidative stress to improve mitochondrial function and autophagy leading to reduction of amyloid‐beta plaques and decreased tau tangles	NCT07278492	Brigham and Women's Hospital	Apr, 2026	Mar, 2028
Mivelsiran	DTT; biologic	Amyloid‐beta	RNAi to decrease APP and downstream Aβ‐related events	NCT05231785	Alnylam Pharmaceuticals	Feb, 2022	Mar, 2029
Nicotinamide riboside	DTT; small molecule	Metabolism and bioenergetics	Mitochondrial function enhancer and antioxidant	NCT04430517	Mclean Hospital	Mar, 2022	Jan, 2026
NIO752	DTT; biologic	Tau	Anti‐tau antisense oligonucleotide	NCT05469360 NCT06372821	Novartis Pharmaceuticals University College, London	Feb, 2023 Nov, 2024	Sep, 2026 Jul, 2026
NPT 2042	STT; cognition enhancer	Neurotransmitter receptors	Modulates the sodium‐potassium‐chloride co‐transporter 1 (NKCC‐1) implicated in disrupting the balance of excitatory and inhibitory neurotransmission by increasing intracellular chloride levels and deceasing gamma‐amino butyric acid (GABA) activity	NCT07222878	NeuroPro Therapeutics, Inc.	Sep, 2025	Oct, 2025
OLX‐07010	DTT; small molecule	Tau	Inhibits tau self‐aggregation	NCT05696483	Oligomerix, Inc	Jan, 2023	Jan, 2026
Phenserine	DTT; small molecule	Cell death	Translational regulation of APP to decrease Aβ and cell death; cholinesterase inhibitor	NCT06774261	Helse Stavanger HF	Feb, 2025	Dec, 2025
Plasma exchange	DTT; biologic	Inflammation	Removes inflammatory mediators from blood	NCT06234436	Oslo University Hospital	Dec, 2023	Dec, 2024
PMN310	DTT; biologic	Amyloid‐beta	Humanized immunoglobulin monoclonal antibody directed at oligomeric amyloid species	NCT06750432	ProMis Neurosciences, Inc	Dec, 2024	Dec, 2026
Probiotics	DTT; biologic	Gut–brain axis	Target the gut microbiome to decrease inflammation	NCT06181513	University of Nicosia	Dec, 2022	Jul, 2025
Psilocybin	STT; neuropsychiatric (depression)	Neurotransmitter receptors	Serotonin 2A receptor (5‐HT2A) agonist	NCT04123314	Johns Hopkins University	Mar, 2021	Sep, 2026
Recombinant human serum albumin	DTT; biologic	Oxidative stress	Delivers antioxidant properties of albumin	NCT06489015	Protgen Ltd	Jun, 2024	Nov, 2025
REM0045392	DTT; small molecule	Tau	Cytoskeletal protein septin modulator	NCT07016464	reMYND	Mar, 2025	Jun, 2026
RO7812653	DTT; biologic	APOE, lipids, and lipoprotein receptors	ASO to selectively reduce apolipoprotein E mRNA in the brain	NCT07234942	Hoffmann‐La Roche	Jan, 2026	Apr, 2028
THN391	DTT; biologic	Inflammation	Anti‐fibrin antibody blocks binding of fibrin to reduce activation of microglia	NCT06814730	Therini Bio, Inc.	Jul, 2025	May, 2026
Xenon	DTT; small molecule	Inflammation	Modulates microglia to assume a protective phagocytic state	NCT06945614	General Biophysics LLC	Apr, 2025	Dec, 2025

Abbreviations: Aß, amyloid‐beta protein; APOE, apolipoprotein E; APP, amyloid precursor protein; ASO, antisense oligonucleotides; CADRO, Common Alzheimer's Disease Research Ontology; CSF, cerebrospinal fluid; CNS, central nervous system; DTT, disease targeted therapy; STT, symptom targeted therapy.

Based on mechanistic and target information, we classify agents as DTTs or as STTs, depending on whether the declared therapeutic purpose is to impact a specific aspect of the pathophysiology of AD with the intention of delaying the occurrence of symptoms or slowing clinical decline or is intended to improve symptoms present at baseline in the trial (cognitive impairment or NPS). This classification can be ambiguous for some therapies; agents may have multiple therapeutic mechanisms; and drugs may have both DTT and STT properties. We identify the principal therapeutic intent of the agent in the trial based on trial characteristics, literature review, and information from the trial sponsor. We divide DTTs into biologics (e.g., MABs, vaccines, antisense oligonucleotides [ASOs], etc.) and small molecules (e.g., drugs usually taken orally and less than 500 Daltons in molecular weight). We divide STTs into those with putative cognition enhancing properties and those intended to ameliorate NPS such as psychosis, agitation, or depression.

In this report, we do not include trials of non‐pharmacologic therapeutic approaches such as exercise, lifestyle interventions, cognitive–behavior therapies, caregiver interventions, supplements, or medical foods. We do not include trials of devices, gene therapies, or stem cell therapies. We do not include biomarker trials if there is no intervention.

3. RESULTS

3.1. Overview

On the Index Date of January 1, 2026, we identified 192 clinical trials for AD assessing 158 drugs. This included 54 trials assessing 36 drugs in Phase 3; 89 trials assessing 84 drugs in Phase 2; and 49 trials assessing 45 drugs in Phase 1 (Figure 1). Twelve of the 192 trials in the pipeline are long‐term extensions of trials with treatment by the agent used in a prior trial.

FIGURE 1.

Agents in clinical trials for treatment of AD on the Index Date of January 1, 2026, as recorded on clinicaltrials.gov. The inner ring shows Phase 3 agents; the middle ring includes Phase 2 agents; the outer ring presents Phase 1 therapies. Agents in green areas are biologics; those in purple areas are disease modifying small molecules; agents in orange areas are symptomatic agents addressing cognition enhancement; and those in the blue sections of the figure target behavioral and neuropsychiatric symptoms. The shape of the icon denotes the population of the trial; the color of the icon denotes the CADRO‐based class of the agent (J. L. Cummings). AD, Alzheimer's disease; CADRO, Common Alzheimer's Disease Research Ontology; Tx, therapy.

The AD drug development pipeline is comprised primarily of DTTs. There are 116 DTTs representing 73% of drugs in development; DTTs account for 134 (70%) of current clinical trials. Sixty‐two (53%) of DTTs are small molecules and 54 (47%) are biological therapies. Phase 3 is comprised of 21 (58%) DTTs; Phase 2 has 61 (73%) DTT agents; Phase 1 has 39 (87%) DTTs. Twenty‐nine of the drugs in the pipeline (18% of agents in trials) are putative cognition enhancers, and 16 (10% of agents in trials) drugs target NPS.

Seventeen of the CADRO categories of AD pathophysiology are targeted by at least one drug in current clinical trials. Thirty‐eight drugs (24%) in the pipeline target neurotransmitter receptors; 28 agents (18%) address inflammation/immune processes; 25 treatments (16%) target Aß protein‐related pathophysiology; 15 agents (9%) target tau‐related processes; eight drugs (5%) address synaptic plasticity/neuroprotection; seven therapies (4%) target metabolism and bioenergetics; five drugs (3%) target growth factors and hormones; four drugs (3%) are posited to treat oxidative stress, and four (3%) address proteostasis/proteinopathy processes; three agents (2%) target vascular pathology of AD; two agents (1%) each target APOE/lipids, gut–brain axis, circadian rhythm disturbances, and epigenetic factors; one (0.6%) each target neuronal loss and neurogenesis; and nine (6%) drugs are described as multi‐target agents.

Fifty‐nine trials (31% of currently active trials) in the AD drug development pipeline are new since the last Index Date (January 1, 2025). There are 14 (26% of Phase 3 trials) new trials in Phase 3, 27 (30% of Phase 2 trials) new trials in Phase 2, and 18 (37% of Phase 1 trials) new trials in Phase 1. Of trials that were active in the pipeline on the Index Date (January 1, 2025) of the last report, 34 clinical trials were completed, nine were terminated, two were withdrawn, and eight are of unknown status (no activity registered on clinicaltrials.gov in the past 2 years).

Repurposed agents approved for non‐AD indications include 56 drugs (35% of drugs in current trials) and 73 (38%) currently active trials. Among the repurposed drugs, six (11%) are DTT biologics, 32 (57%) are DTT small molecules, 12 (21%) are putative cognition enhancers, and eight (14%) are being assessed for the treatment of NPS (some agents are being assessed for both cognition enhancement and NPS). Repurposed agents account for 11% of DTT biologics, 52% of DTT small molecules, 41% of cognition enhancing agents, and 50% of treatments for NPS in the AD drug development pipeline.

All stages of the AD continuum are represented in current clinical trials. Ten trials (5%) involve cognitively unimpaired persons with biomarker or genetic evidence of AD; 67 trials (35%) include participants with MCI due to AD or prodromal AD (with or without biomarker confirmation of AD pathology); 52 trials (27%) involve participants with early AD (MCI or mild AD dementia); 102 trials (53% of active trials) enroll patients with mild AD dementia; and 63 trials (33%) include participants with moderate or severe AD dementia (with or without biomarker confirmation of AD pathological changes). (Some participant categories overlap accounting for why the sum of all the trials listed exceeds the number of active trials.)

Of all currently active trials for which geographic data are given (N = 177), 65 (37%) are conducted only in North America; 59 (33%) include only areas outside of North America; and 53 (30%) include clinical trial sites both in North America and outside of North America (e.g., are “global”).

The biopharmaceutical industry sponsors 113 (59%) of all clinical trials in the current AD pipeline, including 39 (72%) Phase 3 trials; 43 (48%) Phase 2 trials; and 31 (63%) Phase 1 trials.

3.2. Phase 3 trials

There are 54 Phase 3 trials studying 36 drugs (Index Date January 1, 2026; Table 1; Figure 2). Of the agents in Phase 3, 21 (58%) are DTTs; nine (25%) target cognition enhancement; and six (17%) address NPS (one STT is for an “other” indication, i.e., seizures). Of the DTTs, 10 (47%) are small molecules and 11 (52%) are biologics. There are five prevention trials assessing DTTs in the Phase 3 AD pipeline, five assessing biologic DTTs, and one studying a DTT small molecule (one trial is assessing both a biologic and a small molecule). Seven trials (13% of Phase 3 trials) are long‐term extensions of trials of drugs that have completed a prior trial of the same drug.

FIGURE 2.

Mechanisms of action of agents in Phase 3 Alzheimer clinical trials as classified using four categories of therapeutic purpose (left) or the CADRO categories (right) (Index Date: January 1, 2026) (J. L. Cummings). CADRO, Common Alzheimer's Disease Research Ontology.

There are four Phase 3 trials focusing on preclinical AD, eight trials for MCI/prodromal participants; 15 trials for participants with early AD; 32 trials for mild AD dementia participants; and 25 and nine trials for participants with moderate or severe AD dementia, respectively (categories are not mutually exclusive and total more than 100%).

Fifteen (42%) Phase 3 agents are repurposed, originating in a non‐AD indication or repositioned in an industry drug development pipeline. Six (40%) of the repurposed agents in Phase 3 are DTTs, four are small molecules, and two are biologics. Five (33%) Phase 3 repurposed agents are putative cognition enhancing agents, and four (27%) Phase 3 repurposed agents are being developed to treat NPS. One STT agent is being developed for treatment of seizures in AD.

There are 14 new trials in Phase 3 (26% of Phase 3 trials). Compared to the last Index Date (January 1, 2025), two Phase 3 trials were completed, six trials were terminated, and one trial is of unknown status (no recorded activity for 2 years).

Eight CADRO categories of AD pathophysiology are targeted by at least one drug in current Phase 3 clinical trials (Figure 3). Fourteen drugs (39%) target neurotransmitter receptors; 10 agents (28%) address aspects of Aß pathophysiology; three (8%) address metabolic and bioenergetic processes; two (5%) each target inflammation/immune processes or proteostasis/proteinopathy; one (3%) each address growth factors and hormones or synaptic function; three (8%) have multiple pathophysiologic targets.

FIGURE 3.

Alzheimer‐related processes as categorized by the CADRO for agents in each phase of the Alzheimer's drug development pipeline (Index Date: January 1, 2026) (J. L. Cummings). CADRO, Common Alzheimer's Disease Research Ontology.

The biopharmaceutical industry sponsors 39 (72%) Phase 3 trials and 22 (61%) Phase 3 drugs. Biopharmaceutical companies sponsor seven repurposed agents in Phase 3 trials (47% of Phase 3 repurposed agents) compared to 15 (62%) novel, non‐repurposed agents in Phase 3 trials.

Review of the global distribution of Phase 3 trials reveals that six (12%) are conducted only in North America; 12 (24%) are conducted only outside North America; and 31 (63%) are conducted in both North American and non–North American regions (location data are unavailable for five trials). Phase 3 trials require 38,417 participants, accounting for 70% of the 54,728 participants needed to populate all currently active AD trials.

3.3. Phase 2 trials

There are 89 Phase 2 trials in the 2026 AD drug development pipeline, comprising 46% of all currently active trials. Phase 2 involves 84 unique drugs representing 53% of all pharmacologic therapies in active AD trails (Table 2; Figure 4). Of the agents in Phase 2, 61 (72% of Phase 2 drugs) are DTTs; 17 (20%) target cognition enhancement; and eight (9%) address NPS. Of the DTTs, 23 (38%) are biologics and 38 (62%) are small molecules.

FIGURE 4.

Mechanisms of action of agents in Phase 2 Alzheimer clinical trials as classified using four categories of therapeutic purpose (left) or the CADRO categories (right) (Index Date: January 1, 2026) (J. L. Cummings). CADRO, Common Alzheimer's Disease Research Ontology.

Thirty‐eight (45%) Phase 2 agents are repurposed. Twenty‐eight (74%) repurposed drugs in Phase 2 are DTTs, including one (11% of Phase 2 repurposed agents) biologic DTT and 24 (63% of Phase 2 repurposed agents) small molecule DTTs. Seven (18%) Phase 2 repurposed agents are putative cognition enhancing agents, and four (11%) Phase 2 repurposed agents are being developed to treat NPS.

There are four long‐term extension trials for participants that have completed a prior trial of the same agent (4% of Phase 2 trials).

There are 2 trials of preclinical AD populations in Phase 2; 40 trials for MCI/prodromal AD participants; 27 trials including participants with early AD; 56 trials for mild AD participants; and 33 and eight trials including moderate and severe AD dementia, respectively (categories are not mutually exclusive, allowing the sum to exceed 100%). There are six (7%) trials among the 89 Phase 2 trials in the AD pipeline aiming to forestall (prevent) some aspect of AD.

Among the 89 active Phase 2 trials, 27 (30%) are new to the pipeline since January 1, 2025.Compared to the last Index Date (January 1, 2025), 17 Phase 2 trials were completed, three trials were terminated, two trials were withdrawn, and three trials are of unknown status (no recorded activity for 2 years).

Sixteen CADRO categories of AD pathophysiology are targeted by at least one drug in current Phase 2 clinical trials (Figure 3). Nineteen drugs (23% of Phase 2 agents) in the AD pipeline target neurotransmitter receptors and 19 (23%) target inflammation/immune dysfunction. Eight drugs (9%) each target Aß or tau biology; five agents (6%) address synaptic plasticity; three drugs (3%) each, target vascular factors or growth factors and hormones; two agents (2%) target oxidative stress and two target circadian rhythm disturbances; and one drug (1%) targets each of the APOE/lipids, neurogenesis, proteostasis/proteinopathy, metabolism and bioenergetics, gut–brain axis, and epigenetic regulator processes. Seven (8%) Phase 2 drugs are reported to be multi‐modal targeting agents, and two (2%) had undisclosed mechanisms.

The biopharmaceutical industry sponsors 43 (48%) of Phase 2 trials. Biopharmaceutical companies sponsor six (16%) repurposed agents in Phase 2 trials and 35 (76%) novel, non‐repurposed agents in Phase 2.

Review of the global distribution of Phase 2 trials with location information reveals that 39 (48%) are conducted only in North America; 24 (30%) are conducted only outside North America; and 18 (22%) are conducted at both North American and non–North American regions.

3.4. Phase 1 trials

Phase 1 of the 2026 AD drug development pipeline includes 49 trials assessing 45 drugs (Index Date January 1, 2026; Table 3). Of the agents in Phase 1, 39 (87%) are DTTs; three (7%) target cognition enhancement; and three (7%) address NPS. Of the DTTs, 24 (62%) are biologics and 15 (38%) are small molecules.

There are six (13%) repurposed agents in Phase 1 trials. Five of the six repurposed agents are DTTs, including one biologic and four small molecules. One Phase 1 repurposed agent is being developed to treat NPS. There is one long‐term extension trial of an agent that had been assessed in a completed trial of the same agent.

There are 22 (45%) Phase 1 trials testing AD‐relevant drugs and comprised of healthy volunteers with no clinical or biomarker evidence of AD. Four (8%) Phase 1 trials include participants with preclinical AD; 19 (39%) Phase 1 trials involve MCI participants; 10 (20%) trials include participants with early AD; 14 (29%) trials involve mild AD dementia; and five (10%) include participants with moderate AD dementia. There are no Phase 1 trials specifically for participants with severe AD; one trial includes participants with AD dementia of unspecified severity (categories are not mutually exclusive).

There are 18 new trials in Phase 1 comprising 37% of the trials in this phase of the AD pipeline. Compared to the last Index Date (January 1, 2025), 15 Phase 1 trials were completed, no Phase 1 trials were terminated or withdrawn, and four trials are of unknown status (no recorded activity for 2 years).

Processes involved in 13 CADRO categories of AD pathophysiology are targeted by at least one drug in current Phase 1 clinical trials (Figure 3). The CADRO categories of amyloid, tau, and inflammation/immune dysfunction each has eight (18% of the Phase 1 drugs for each of these targets) related agents in Phase 1 trials. Six (13%) drugs in Phase 1 target neurotransmitter receptors, and three (7%) address metabolic/bioenergetic targets. Two agents (4%) are being developed for each of the categories of oxidative stress and synaptic plasticity. One (2%) agent is in development for each of the CADRO targets involved of APOE/lipids, cell death, proteostasis/proteinopathy, growth factors and hormones, gut–brain axis, and epigenetic regulators. There were two Phase 1 agents (4%) with undisclosed mechanisms.

The biopharmaceutical industry sponsors 31 (63%) Phase 1 trials. Biopharmaceutical companies sponsor one of six Phase 1 trials for repurposed agents and 30 (70%) trials of novel, non‐repurposed agents in Phase 1.

Review of the global distribution of Phase 1 trials reveals that 20 (43%) are conducted only in North America; 23 (49%) are conducted only outside North America; and four (8%) are conducted in both North American and non–North American regions. Phase 1 trials collectively require 2,350 participants for the currently registered trials.

3.5. Longitudinal trial observations

The annual review of the AD drug development pipeline began in 2016 allowing longitudinal review of pipeline activity. We assessed the number of trials and the number of agents in the pipeline over the decade of 2017–2026. The number of trials increased by approximately 35%, and the number of agents in trials increased by approximately 40% during this interval (Figure 5A). The number of trials active in the pipeline is the sum of new trials that have entered since the previous Index Date and previously registered trials that have not yet completed. Examination of the three most active areas of DTT drug development revealed that the percentage of the pipeline devoted to inflammation/immune dysfunction drugs has increased from 6% to approximately 20%, tau targeted agents have increased from 6% to approximately 20%, and amyloid targeted agents have decreased from 33% of the pipeline to approximately 20% of agents in the pipeline (Figure 5B). The percentage of inflammation/immune dysfunction drugs and of amyloid targeted agents has been stable since 2022.

FIGURE 5.

(A) The number of trials and the number of agents in the AD drug development pipeline over the decade of 2017–2026. (B) The percent of drugs in the pipeline accounted for by inflammation/immune dysfunction, tau, and amyloid targeted agents during the 2017–2026 interval. AD, Alzheimer's disease.

3.6. Biomarkers in trials

Most active trials include a biomarker in the trial design — 47 Phase 3 trials (87%), 79 Phase 2 trials (89%), and 33 Phase 1 trials (67%) — include a biomarker for at least one context of use. Among the 192 clinical trials, 96 (50%) have an inclusion biomarker for trial eligibility, with amyloid positron emission tomography (PET) identified as the most common biomarker modality (N = 49). Fluid biomarkers are used for inclusion in 58 (60% if trials in which an inclusion biomarker was incorporated) trials, 44 trials measure biomarkers in cerebrospinal fluid (CSF) analytes, 26 trials measure blood‐based biomarkers, and one trial has saliva as a biomarker source.

Fifty‐two (27%) active AD trials have a biomarker as a primary outcome measure (nine in Phase 3, 32 in Phase 2, and 11 in Phase 1) with or without a clinical measure as a concomitant primary outcome. Imaging was used as a primary outcome in 29 trials (56% if trials in which a biomarker functioned as a primary outcome) (one trial had ocular imaging as a primary outcome). There are 43 trials (46% of trials with biomarker as a primary outcome) using a fluid biomarker as a primary outcome measure; with 16 measuring a blood‐based biomarker, 10 measuring CSF analytes, one measuring exosomes from an undefined fluid, and one measuring changes in stool samples. Aβ biomarkers are used as a primary outcome measure in 16 trials (31% of trials with a primary outcome biomarker; five in Phase 3, nine in Phase 2, and two in Phase 1), and tau biomarkers are used in 14 trials (27% of trials with a biomarker as a primary outcome; two in Phase 3, nine in Phase 2, three in Phase 1). The most common outcome biomarkers are Aβ PET (11), MRI (eight), and tau PET (four).

3.7. Trial participants

To fully populate currently active trials, 54,728 participants are required: 38,417 in Phase 3; 13,961 in Phase 2; and 2,350 in Phase 1. Of the total number of required participants, 70% are needed for Phase 3 trials, 26% are required for Phase 2 trials, and 4% for Phase 1 trials.

Trial participants are divided among trials for DTTs (39,390; 72% of participants); trials for cognition enhancing agents (6,658; 12%); trials for dugs addressing NPS (8,560 participants; 16%); and trial for “other” symptoms (120; 0.2%).

3.8. Global trial distribution

Phase 3 trials require the largest number of patients and correspondingly the largest number of sites and participating regions. Sixty‐three percent of Phase 3 trials include both North American and non–North American sites; 22% of Phase 2 trials include both North American and non–North American sites; and 9% Phase 1 trials are conducted in North American and non–North American sites. Forty‐seven of 53 (89%) global trials are sponsored by the biopharmaceutical industry.

Five percent of DTT small molecule trials are conducted globally; 50% of DTT biological agent trials are conducted globally; 23% of trials for cognition enhancing agents are global; and 42% of trials for NPS therapies are conducted globally.

We calculated the global distribution of unique clinical trial sites active on the Index Date (January 1, 2026) and found that there are 3156 sites in North America and 3607 sites in non–North American regions including 1363 in Western Europe/Israel, 661 in Eastern Europe/Russia, 571 in Asia (not including Japan), 516 in Japan, 321 in South America/Mexico, and 175 in South Africa, Australia, or New Zealand.

3.9. Repurposed agents

The 56 repurposed agents and 73 trials of repurposed drugs in the 2026 AD drug development pipeline represent 35% of the total number of drugs in trials and 38% of all trials. Repurposed agents account for 42% of drugs in Phase 3, 45% of drugs in Phase 2, and 13% of drugs in Phase 1. Of repurposed agents in trials, 57% are DTT small molecules, 11% are DTT biological agents, 21% are STTs addressing cognition enhancement, and 14% are STTs for NPS of AD. The biopharmaceutical industry sponsors most of the repurposed agents in Phase 3 (47%; N = 7) and relatively fewer of the repurposed drugs in Phase 2 (16%; N = 7) and Phase 1 (6%; N = 1).

3.10. Trial funders

The biopharmaceutical industry sponsors 59% of all clinical trials in the 2026 AD drug development pipeline, including 72% of Phase 3 trials, 48% of Phase 2 trials, and 63% of Phase 1 trials. Biopharmaceutical industry‐sponsored trials account for 42% of DTT small molecule trials, 68% of DTT trials of biological agents, 57% of trials of cognition enhancers, and 78% of STTs trials addressing NPS. Non‐industry funders include federal agencies (e.g., NIH in the United States, non‐US governmental agencies), philanthropic and advocacy organizations, academic medical centers, and public‐private collaborations (if industry is not identified as the lead sponsor).

3.11. Combination therapies

There are few trials involving combination therapies in the 2026 pipeline. Phase 3 combination trials include MABs targeting tau and Aß (NCT01760005; NCT05269394), a gamma secretase modulator plus an anti‐Aß plaque MAB (NCT06996730), a combination of a dopamine agonist (rotigotine) and a cholinesterase inhibitor (rivastigmine) (NCT06702124), and a combination of a muscarinic cholinergic agonist (xanomeline) and a peripheral cholinergic antagonist (trospium) (KarXT 10 trials). Phase 2 combination trials include a tau vaccine and an anti‐Aß MAB (NCT07167966), MABs targeting tau and Aß (NCT06602258), two agents targeting hypertension to determine the impact on tau and Aß (NCT05331144), and a combination of a repurposed antibiotic (ciprofloxacin) and repurposed anti‐inflammatory agent (celecoxib)(NCT06185543). The combination of two reverse transcriptase inhibitors (emtricitabine plus tenofovir alafenamide) is being assessed in a Phase 1 clinical trial involving participants with MCI (NCT07210528). Most trial descriptions on clinicatrials.gov do not specify if patients on MABs are eligible for participation; those allowing participants on MABs may be viewed as assessing combination therapies.

3.12. Drugs scheduled to complete Phase 3 and Phase 2 trials in 2026

Eight Phase 3 trials will reach their primary completion date in 2026 including trials of AR1001, a phosphodiesterase 5 (PDE 5) inhibitor (NCT05531526); caffeine, an adenosine receptor blocker (NCT04570085); donepezil, an acetylcholinesterase inhibitor (NCT04661280); metformin, an insulin sensitizer (NCT04098666); valiltramiprosate, an amyloid anti‐aggregation agent (NCT06304883); Wujia Yizhi, a Chinese herbal therapy (NCT06534723); and a muscarinic cholinergic agonist, xanomeline plus trospium for the treatment of AD psychosis (NCT05511363; NCT06585787). The Phase 3 trial of donanemab in preclinical AD (NCT05026866) could read out in 2026 if enough events occur to trigger the analysis in the time‐to‐event design. In addition, there are 11 drugs in 14 Phase 3 trials scheduled for primary completion prior to 2026 that have not been reported as completed, terminated, or withdrawn. These trials could have end‐of‐study reports in 2026.

Twenty‐nine Phase 2 clinical trials will be completed in 2026 providing information across a variety of Aß, tau, hormonal, senolytic, inflammatory, transmitter, epigenetic, and vascular disease processes. In addition, there are 19 drugs in 21 Phase 2 trials whose primary completion date was reported to be prior to 2026 and have not yet been updated on clinicaltrials.gov as completed, terminated, or withdrawn. These delayed trial reports could provide information in 2026.

4. DISCUSSION

The 192 clinical trials and 158 novel agents in the 2026 AD drug development pipeline expands on the 182 clinical trials assessing 138 drugs present in the 2025 pipeline. The 59 new trials registered since the Index Date of January 1, 2025, is only slightly larger than the 56 new trials initiated in the previous year. The larger number of active trials observed in 2026 may reflect longer treatment and recruitment periods with fewer trial completions in the past year.

Biomarkers have transformed clinical trials with the ability to confirm the diagnosis of AD for trial eligibility, stratify or enroll patients based on likelihood of progression, monitor therapeutic effects longitudinally, and verify the pharmacodynamic effect of the candidate therapy as a study outcome. ⁷ Fifty percent of current trials use a biomarker for eligibility. Many currently active trials were registered before diagnostic biomarkers were widely available, and it is anticipated that the proportion of trials using diagnostic biomarkers will increase. Twenty‐seven percent of trials have a biomarker as a primary outcome measure (with or without a clinical measure as a concomitant primary outcome). These trials anticipate a change in the biomarker to verify the mechanism of action, demonstrating substantial optimism for the biomarker's pharmacodynamic performance.

Compared to the 2025 pipeline, the 2026 pipeline has more transmitter‐based treatment candidates (plus eight), multi‐target agents (plus six), inflammatory/immune function modulating drugs (plus four), epigenetic drugs (plus two), and more agents addressing oxidation, cell death, proteostasis/proteinopathies, and circadian rhythm disturbances (plus one each). In 2026, there are fewer drugs addressing in the pipeline for neurogenesis, metabolism and bioenergetics, and synaptic plasticity (one fewer in each category). Between 2025 and 2026, there have been no changes in the number of drugs addressing targets related to Aß, tau, APOE/lipids, vasculature, growth factors and hormones, or the gut–brain axis.

Seventeen CADRO categories are represented among the targeted disease processes addressed by drugs in the 2026 pipeline. For each CADRO target process, numerous drug MoAs are included. For example, the inflammation/immune dysfunction category includes 10 agents targeting primarily the microglia, nine targeting cytokines, six addressing both microglia and cytokines, and three directed at some other inflammation/immune related function. In addition, several agents in the multi‐target category are posited to have important effects on inflammation and immune function. Together, the total number of mechanisms represented among drugs in the pipeline is very large and is anticipated to be informative regarding key disease processes and the consequences of modulating them.

There are 56 repurposed drugs in the 2026 pipeline (35% of pipeline drugs) compared to 46 repurposed agents (33% of the pipeline) in 2025. Our analyses demonstrate that involvement of industry in repurposing differs substantially from its involvement in development of novel compounds. In Phase 2, industry is responsible for advancing six repurposed agents and 35 novel agents; this contrasts with non‐industry sponsors that are advancing 11 novel agents and 32 repurposed agents. In Phase 3, industry is advancing 15 novel agents and eight repurposed agents; non‐industry sponsors are advancing nine novel agents and eight repurposed agents. Repurposing represents 16% of the industry pipeline and 57% of the non‐industry pipeline. Our observations suggest that industry sponsors typically assess few repurposed compounds in Phase 3, possibly reflecting the lack of intellectual property for many of the generic agents and the difficulty of generating a return on investment required for development of these agents. The pattern emphasizes the importance of repurposing in Phase 2 as an opportunity for non‐industry sponsors such as academic medical centers to advance research workforce training, drug development tool creation, and trial infrastructure development. ⁸ These activities translate to benefits for drug development by all sponsors across the drug development ecosystem.

This report has important limitations. All data are derived from clinicaltrials.gov. This registry is comprehensive but not exhaustive, and some drugs in clinical trials — particularly those conducted in non–North American sites — may not be registered and are not included in this report. Registration of US trials on clinicaltrials.gov is mandated but not completely standardized and irregularities of data entry could affect our report. We assign categories of DTT or STT based on clinicaltrials.gov, sponsor information, and published reports. These categories may not accurately characterize the intended purpose of all compounds. Our database team adheres to good practices in data management and governance, but errors in data capture or interpretation are possible. ⁹ , ¹⁰

This review of currently active AD clinical trials and the drugs being assessed indicates that AD drug development is a robust enterprise with an increased number of trials and drugs in trials in 2026 compared to 2025 and an approximately 40% increase in drugs and trials since 2017. A diverse array of pathophysiological processes is addressed by drugs in the pipeline. Biomarkers are increasingly used for trial eligibility as well as being integrated as pharmacodynamic outcomes. Phase 2 proof‐of‐concept studies are the innovation engines of AD drug development and are populated by the largest number of trials in the pipeline. Non‐industry sponsors account for a substantial number of Phase 2 trials (52%). There have been no new drug approvals for AD since 2023, and the overall failure rate of AD drug development is high. Better target identification, improved ascertainment of potentially responsive patient populations, enhanced use of biomarkers to inform understanding of drug effects, and more stringent criteria for advancing drugs to late‐stage development are anticipated to improve the success rate of AD drug development.

CONFLICT OF INTEREST STATEMENT

Jeffrey L. Cummings has provided consultation to Acadia, Acumen, ALZpath, AnnovisBio, Artery, Axsome, Biogen, Bristol‐Myers Squib, Eisai, Fosun, GAP Foundation, Hummingbird Diagnostics, IGC, Janssen, Julius Clinical, Kinoxis, Lilly, LSP/eqt, Merck, MoCA Cognition, Novo Nordisk, NSC Therapeutics, Otsuka, ReMYND, Roche, Scottish Brain Sciences, Signant Health, Simcere, sinaptica, and T‐Neuropharmaceutical, assessment, and investment companies. Kate Zhong is CEO of CNS Innovations. Yadi Zhou, Amanda Leisgang Osse, and Jorge Fonseca declare no competing interests. Author disclosures are available in the Supporting Information.

CONSENT STATEMENT

Not applicable. All data are from an anonymized publicly available clinical trial registry (clinicaltrials.gov). No individual participant‐level data are available on the registry.

Supporting information

Supporting Information

DATA AVAILABILITY STATEMENT

Data are available in summary form on alzpipeline.com. Data will be made available through the AD work bench of the Gates Ventures’ Alzheimer's Disease Data Initiative.