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Alzheimer's disease drug development pipeline: 2017
Open accessAbstract
Introduction: There is an urgent need to develop new treatments for Alzheimer's disease (AD) and to understand the drug development process for new AD therapies. Methods: We assessed the agents in the AD pipeline as documented in clinicaltrials.gov for phase I, phase II, and phase III, accessed 1/5/2017. Results: There are 105 agents in the AD treatment development pipeline, of which 25 agents are in 29 trials in phase I, 52 agents are in 68 trials in phase II, and 28 agents are in 42 trials in phase III. Seventy percent of drugs in the AD pipeline are disease‐modifying therapies (DMTs). Fourteen percent are symptomatic cognitive enhancers, and 13% are symptomatic agents addressing neuropsychiatric and behavioral changes (2% have undisclosed mechanisms). Most trials are sponsored by the biopharmaceutical industry. Trials include patients with preclinical AD (cognitively normal with biomarker evidence of AD), prodromal AD (mild cognitive symptoms and biomarker evidence of AD), and AD dementia. Biomarkers are included in many drug development programs particularly those for DMTs. Thirteen of 46 phase II DMT trials have amyloid imaging as an entry criterion, and 10 of 28 phase III trials incorporate amyloid imaging for diagnosis and entry. A large number of participants are needed for AD clinical trials; in total, 54,073 participants are required for trials spanning preclinical AD to AD dementia. When compared with the 2016 pipeline, there are eight new agents in phase I, 16 in phase II, and five in phase III. Discussion: The AD drug development pipeline has 105 agents divided among phase I, phase II, and phase III. The trials include a wide range of clinical trial populations, many mechanisms of action, and require a substantial number of clinical trial participants. Biomarkers are increasingly used in patient identification and as outcome measures, particularly in trials of DMTs.
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“A number of additional pathogenic mechanisms have been described, possibly overlapping with Aβ plaques and NFT formation or induced by them, including inflammation, oxidative damage, iron deregulation, and cholesterol metabolism blood-brain barrier (BBB) dysfunction or α-synuclein toxicity.9-13”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [12]
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Cites
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059 · cited 1×
“Aducanumab targets multiple Ab species, has had an encouraging phase I/II trial, and is continuing in phase III [35].”
BackgroundAlzheimer’s disease drug-development pipeline: Few candidates, frequent failures
Cummings, J. L., Morstorf, T., & Zhong, K. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt269 · Cited by 1,744 · cited 1×
“Although there are promising agents in the pipeline that could achieve this goal, it is clear that given the high rate of failure of AD drug development [38], the aim of having a repertoire of agents that could respond comprehensively and individually to a patient’s clinical circumstances within the 2025 timeframe is…”
BackgroundSelf-citation2015 Alzheimer's disease facts and figures
Alzheimer's Association (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.02.003 · Cited by 1,673
Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework
Cook, D., Brown, D., Alexander, R., March, R., Morgan, P., Satterthwaite, G., & Pangalos, M. N. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4309 · Cited by 1,344 · cited 1×
“Biomarkers can contribute substantially to drug development success [39].”
BackgroundClinical Trial Registration: A Statement from the International Committee of Medical Journal Editors
De Angelis, C., Drazen, J. M., Frizelle, F. A., Haug, C., Hoey, J., Horton, R., Kotzin, S., Laine, C., Marusic, A., Overbeke, A. J. P. M., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejme048225 · Cited by 1,241
Sperling, R. A., Jack, C. R., Black, S. E., Frosch, M. P., Greenberg, S. M., Hyman, B. T., Scheltens, P., Carrillo, M. C., Thies, W., Bednar, M. M., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.05.2351 · Cited by 857
Lombardo, I., Ramaswamy, G., Piscitelli, S. C., & Friedhoff, L. T. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.08.154 · Cited by 656
Weiner, M. W., Veitch, D. P., Aisen, P. S. S., Beckett, L. A., Cairns, N. J., Green, R. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Morris, J. C., et al. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.10.006 · Cited by 523
Drug development in Alzheimer’s disease: the path to 2025
Cummings, J., Aisen, P. S., DuBois, B., Frölich, L., Jack, C. R., Jones, R. W., Morris, J. C., Raskin, J., Dowsett, S. A., & Scheltens, P. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0207-9 · Cited by 459 · cited 3×
“This means that under current circumstances, an agent must now be in phase II to possibly be approved by 2025 [5].”
BackgroundSelf-citationGauthier, S., Feldman, H. H., Schneider, L. S., Wilcock, G. K., Frisoni, G. B., Hardlund, J. H., Moebius, H. J., Bentham, P., Kook, K. A., Wischik, D. J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31275-2 · Cited by 427 · cited 1×
“Leuco-methylthioninium (LMTM) (or TRx0237) derived from methylene blue and addressing tau aggregation completed its phase III trials in 2016 and failed to meet prespecified outcomes of the trial [22]; however, its open-label extension study is listed as ongoing.”
BackgroundTrial Reporting in ClinicalTrials.gov — The Final Rule
Zarin, D. A., Tse, T., Williams, R. J., & Carr, S. (2016) · New England Journal of Medicine · doi:10.1056/nejmsr1611785 · Cited by 332 · cited 1×
“the trial [7], but not all sponsors meet this deadline.”
BackgroundVassar, R., Kuhn, P., Haass, C., Kennedy, M. E., Rajendran, L., Wong, P. C., & Lichtenthaler, S. F. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12715 · Cited by 311
Issues in the Registration of Clinical Trials
Zarin, D. A., Ide, N. C., Tse, T., Harlan, W. R., West, J. C., & Lindberg, D. A. B. (2007) · JAMA · doi:10.1001/jama.297.19.2112 · Cited by 228 · cited 1×
“The data provided may not represent the entire universe of AD drug development [23].”
Backgroundβ-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease
Menting, K. W., & Claassen, J. A. H. R. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00165 · Cited by 144
Toward a New Era of Trust and Transparency in Clinical Trials.
Hudson, K., Lauer, M., & Collins, F. (2016) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.2016.14668 · Cited by 132
Commercializing biomedical research through securitization techniques
Fernandez, J.-M., Stein, R. M., & Lo, A. W. (2012) · Nature Biotechnology · doi:10.1038/nbt.2374 · Cited by 124 · cited 1×
“New investment vehicles are needed, and some have been proposed such as private-federal bonds [41,42].”
BackgroundBiomarkers in Alzheimer's disease drug development
Cummings, J. L. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.06.004 · Cited by 122
Self-citationAlzheimer's drug‐development pipeline: 2016
Cummings, J., Morstorf, T., & Lee, G. (2016) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2016.07.001 · Cited by 108 · cited 2×
“This closely resembles the pipeline as it appeared in 2016 where 73% were DMTs, 18% cognitive enhancers, and 9% psychotropic agents [4].”
BackgroundSelf-citationRevolutionizing Alzheimer's disease and clinical trials through biomarkers
Mattsson, N., Carrillo, M. C., Dean, R. A., Devous, M. D., Nikolcheva, T., Pesini, P., Salter, H., Potter, W. Z., Sperling, R. A., Bateman, R. J., et al. (2015) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2015.09.001 · Cited by 102
Economic analysis of opportunities to accelerate Alzheimer's disease research and development
Scott, T. J., O’Connor, A. C., Link, A. N., & Beaulieu, T. J. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12417 · Cited by 91 · cited 1×
“A recent analysis of AD drug development showed that it takes on average 13 years for a candidate treatment to move from laboratory to FDA review and 10 years for an agent to navigate the clinical development period from start of phase I to end of FDA review [37].”
A Review: Treatment of Alzheimer’s Disease Discovered in Repurposed Agents
Appleby, B. S., Nacopoulos, D. A., Milano, N. J., Zhong, K., & Cummings, J. L. (2013) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000345791 · Cited by 90 · cited 2×
“Antihypertensive agents, statins, anti-inflammatory agents, calcium channel blockers, and agents with many other MOAs have been proposed as drugswith effects possibly useful in treatingADand can enter AD drug development pipelines at phase II or phase III [15,19,20].”
BackgroundSelf-citationDiscovering New Treatments for Alzheimer's Disease by Repurposing Approved Medications
Appleby, B. S., & Cummings, J. L. (2013) · Current Topics in Medicinal Chemistry · doi:10.2174/15680266113136660162 · Cited by 78 · cited 2×
“Antihypertensive agents, statins, anti-inflammatory agents, calcium channel blockers, and agents with many other MOAs have been proposed as drugswith effects possibly useful in treatingADand can enter AD drug development pipelines at phase II or phase III [15,19,20].”
BackgroundSelf-citationGad, S. C. (2009) · DigitalGeorgetown (Georgetown University Library) · Cited by 66
Merck ends trial of potential Alzheimer’s drug verubecestat
Hawkes, N. (2017) · BMJ · doi:10.1136/bmj.j845 · Cited by 61 · cited 1×
“The first BACE inhibitor trial to be tested in phase III in an AD dementia population was recently terminated for the lack of efficacy [33].”
BackgroundRE-ENGINEERING ALZHEIMER CLINICAL TRIALS: GLOBAL ALZHEIMER’S PLATFORM NETWORK
Cummings, J. L., Aisen, P. S. S., Barton, R. D., Bork, J., Doody, R. S., Dwyer, J. R., Egan, J. C., Feldman, H., Lappin, D. R., Truyen, L., et al. (2016) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2016.93 · Cited by 55 · cited 2×
“This observation underlies recent efforts in the AD drug development arena to advance new methods for patient recruitment including electronic engagement of potential participants, creation of registries of candidate subjects, and providing transportation, neighborhood vans, and insurance-based referral mechanisms to…”
BackgroundSelf-citationFuture Therapeutics in Alzheimer’s Disease: Development Status of BACE Inhibitors
Evin, G. M. (2016) · BioDrugs · doi:10.1007/s40259-016-0168-3 · Cited by 52 · cited 1×
“The published results of phase I testing in both healthy participants and AD populations have demonstrated robust (45%–95%) reductions in CSF amyloid b protein (Ab) levels [31].”
BackgroundJekunen, A. (2014) · Drug Design Development and Therapy · doi:10.2147/dddt.s68579 · Cited by 51 · cited 1×
“, insufficient funding, reprioritization of agents in development, change in company business agenda, and management decision after assessment of the competitive landscape) [21].”
BackgroundParallel Discovery of Alzheimer’s Therapeutics
Lo, A. W., Ho, C., Cummings, J., & Kosik, K. S. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008228 · Cited by 50 · cited 1×
“New investment vehicles are needed, and some have been proposed such as private-federal bonds [41,42].”
BackgroundSelf-citationSolanezumab and the amyloid hypothesis for Alzheimer’s disease
Couteur, D. G. L., Hunter, S., & Brayne, C. (2016) · BMJ · doi:10.1136/bmj.i6771 · Cited by 40 · cited 1×
“It was terminated as a candidate therapy for AD dementia [34].”
BackgroundGlobalization of Alzheimer's disease clinical trials
Cummings, J. L., Reynders, R., & Zhong, K. (2011) · Alzheimer s Research & Therapy · doi:10.1186/alzrt86 · Cited by 38 · cited 1×
“The anticipated recruitment period is often longer than the treatment period, and in many cases, these planned recruitment goals are not met [25,26].”
BackgroundSelf-citationNew directions for protease inhibitors directed drug discovery
Hamada, Y., & Kiso, Y. (2015) · Biopolymers · doi:10.1002/bip.22780 · Cited by 38 · cited 1×
“Advances in small-molecule screening approaches have helped overcome these challenges and facilitated the entry of a number of BACE inhibitors into the pipeline [30].”
BackgroundRepackaging FDA-approved drugs for degenerative diseases: promises and challenges
Cummings, J. L., & Zhong, K. (2014) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2014.884923 · Cited by 32 · cited 2×
“Antihypertensive agents, statins, anti-inflammatory agents, calcium channel blockers, and agents with many other MOAs have been proposed as drugswith effects possibly useful in treatingADand can enter AD drug development pipelines at phase II or phase III [15,19,20].”
BackgroundSelf-citationAdaptive design clinical trials and trial logistics models in CNS drug development
Wang, S., Hung, H., & O’Neill, R. T. (2010) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2010.09.003 · Cited by 30 · cited 1×
“Phases II and III trials are often called “learn” and “confirm” trials, respectively, with phase III intended to confirm effects observed in phase II in larger populations treated for longer periods of time [11,13].”
BackgroundPrinciples and Practice of Pharmaceutical Medicine
Edwards, L. D., Fox, A. W. 1., & Stonier, P. D. (2010) · Wiley eBooks · doi:10.1002/9781444325263 · Cited by 26
Alzheimer's disease research in the context of the national plan to address Alzheimer's disease
Snyder, H. M., Hendrix, J. A., Bain, L. J., & Carrillo, M. C. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2015.06.005 · Cited by 18 · cited 1×
“President Obama articulated a goal of cure or meaningful treatment for AD by the year 2025 [5,36].”
BackgroundThe need for thorough phase II studies in medicines development for Alzheimer’s disease
Gray, J. A., Fleet, D., & Winblad, B. G. (2015) · Alzheimer s Research & Therapy · doi:10.1186/s13195-015-0153-y · Cited by 17 · cited 2×
“Phases II and III trials are often called “learn” and “confirm” trials, respectively, with phase III intended to confirm effects observed in phase II in larger populations treated for longer periods of time [11,13].”
BackgroundPhase I: The First Opportunity for Extrapolation from Animal Data to Human Exposure
Curry, S. H., Decory, H. H., & Gabrielsson, J. (2010) · doi:10.1002/9781444325263.ch9 · Cited by 12
Principles of CNS drug development : from test tube to patient
Kelly, J. J. P. (2009) · Cited by 9
Norfleet, E., & Gad, S. C. (2010) · Pharmaceutical Sciences Encyclopedia · doi:10.1002/9780470571224.pse210 · Cited by 6
Refolo, L. M., & Fillit, H. M. (2006) · Current Alzheimer Research · doi:10.2174/156720506777632853 · Cited by 6 · cited 1×
“Philanthropy and innovative approaches such as venture philanthropy may help accelerate AD drug discovery and development funding [40].”
BackgroundTan, S. B., & Machin, D. (2010) · Pharmaceutical Sciences Encyclopedia · doi:10.1002/9780470571224.pse211 · Cited by 4
Symptomatic Cognitive Enhancing Agents
Cummings, J. L., & Zhong, K. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802173-6.00017-4 · Cited by 4
Self-citationViglietta, V., O'Gorman, J. T., Williams, L. J., Chen, T., EnayetAllah, A. E., Chiao, P., Höck, C., Nitsch, R. M., Haeberlein, S. B., & Sandrock, A. W. (2017) · Neurology · doi:10.1212/wnl.88.16_supplement.s7.003 · Cited by 2
Flagged first, then by citations
3 of the 47 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- Alzheimer's Association, 2015, Changing the Trajectory of Alzheimer's Disease: How a Treatment by 2025 Saves Lives and Dollars
- Tan S.B., 2009, Clinical Trials Handbook, 255
- Babic T., 2016, Improving screen fail and recruitment rates in Alzheimer's disease clinical trials, J Clin Stud, 8, 38
Cited by
Sorted by citations
Diagnosis and Management of Dementia: Review
Arvanitakis, Z., Shah, R. C., & Bennett, D. A. (2019) · JAMA · doi:10.1001/jama.2019.4782 · Cited by 1,561
Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics
Tiwari, S., Atluri, V., Kaushik, A., Yndart, A., & Nair, M. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s200490 · Cited by 1,308
“Table 1 summarizes the drugs specific to amyloid that are being studied andwhich target sufficiently fundamental and proximate degenerative mechanisms.(64,65)”
BackgroundReligious Orders Study and Rush Memory and Aging Project
Bennett, D. A., Buchman, A. S., Boyle, P. A., Barnes, L. L., Wilson, R. S., & Schneider, J. A. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179939 · Cited by 1,260
“Therearecurrentlyabout100drugsintheAD pipelineintheUSAwithanadditional100indevel-opmentintheEuropeanUnionwithparticipants rangingfromthosewithmoderatetosevereAD dementiatoasymptomaticpersons[443,444].”
Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01911-3 · Cited by 1,138
Current and Future Treatments in Alzheimer Disease: An Update
Yiannopoulou, K. G., & Papageorgiou, S. G. (2020) · Journal of Central Nervous System Disease · doi:10.1177/1179573520907397 · Cited by 966
Metadata
- Authors
- Cummings, J., Lee, G., Mortsdorf, T., Ritter, A., & Zhong, K.
- Affiliations
- Cleveland Clinic (US)
- Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas NV USA
- Touro University Nevada Henderson NV USA
- Corresponding author
- Cummings, Jeffrey
- Venue
- Alzheimer's & Dementia: Translational Research & Clinical Interventions
- Publisher
- Wiley
- Published
- 2017-05-24
- Volume
- 3
- Issue
- 3
- Pages
- 367-384
- ISSN
- 2352-8737 (ISSN-L)
- PMC
- PMC5651419
- OpenAlex
- W2617072792
- Cited by
- 549
- References
- 47
- Citations by year
- 2026: 14 · 2025: 53 · 2024: 48 · 2023: 52 · 2022: 67 · 2021: 59 · 2020: 53 · 2019: 91 · 2018: 103 · 2017: 7
- FWCI
- 52.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia Translational Research & Clinical Interventions (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Scholarship - UNLV (University of Nevada Reno) (submittedVersion, cc-by-nc)
- Funders
- National Institute on Aging (R01AG084250 R56AG074001 U01AG073323 R01AG066707 R01AG076448 R01AG082118 RF1AG082211 R21AG083003 R35AG71476)
- National Institute of General Medical Sciences (NIA R25AG083721, NIA R35AG71476, P20GM109025)
- National Institute of Neurological Disorders and Stroke (RF1NS133812)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, drug development pipeline, clinical trials, disease-modifying therapy, prodromal Alzheimer's disease, preclinical Alzheimer's disease, amyloid imaging, biomarkers, clinical trial participants
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