Drug development in Alzheimer's disease: The path to 2025

Alzheimer's Research and Therapy

Volumn 8, Issue 1, 2016, Pages

  Cummings, Jeffrey ^a   Aisen, Paul S ^b   Dubois, Bruno ^c   Frölich, Lutz ^d   Jack, Clifford R ^e   Jones, Roy W ^f   Morris, John C ^g   Raskin, Joel ^h   Dowsett, Sherie A ^h   Scheltens, Philip ⁱ  

^a Lou Ruvo Center for Brain Health   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^c PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^d UNIVERSITY OF HEIDELBERG   (Germany)

^e MAYO CLINIC   (United States)

^f ROYAL UNITED HOSPITAL   (United Kingdom)

^g WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h ELI LILLY AND COMPANY   (United States)

ⁱ VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Alzheimer's disease; Disease modifying therapy 2025

Indexed keywords

ANTICONVULSIVE AGENT; ANTIHYPERTENSIVE AGENT; ANTINEOPLASTIC AGENT; BIOLOGICAL MARKER; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; TAU PROTEIN; NOOTROPIC AGENT;

ALZHEIMER DISEASE; ALZHEIMER DISEASE ASSESSMENT SCALE; ARTICLE; AWARENESS; BASIC RESEARCH; BIOINFORMATICS; CLINICAL ASSESSMENT TOOL; CLINICAL DEVELOPMENT PLAN; COMBINATION DRUG THERAPY; DAILY LIFE ACTIVITY; DISEASE MODEL; DISEASE MODIFYING THERAPY; DISEASE REGISTRY; DRUG APPROVAL; DRUG DEVELOPMENT; DRUG REPOSITIONING; DRUG RESEARCH; FUNCTIONAL ASSESSMENT; FUNDING; HEALTH EDUCATION; HUMAN; MILD COGNITIVE IMPAIRMENT; MINI MENTAL STATE EXAMINATION; NONHUMAN; PALLIATIVE THERAPY; PATIENT PARTICIPATION; PRIORITY JOURNAL; RISK ASSESSMENT; THERAPY; ANIMAL;

ALZHEIMER DISEASE; ANIMALS; DRUG DISCOVERY; HUMANS; NOOTROPIC AGENTS;

EID: 84988384555     PISSN: None     EISSN: 17589193     Source Type: Journal    
DOI: 10.1186/s13195-016-0207-9     Document Type: Article

References (68)

1. Alzheimer's Disease International, 2015. https://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf. Accessed 25 May 2016.
2. Vradenburg G. A pivotal moment in Alzheimer's disease and dementia: how global unity of purpose and action can beat the disease by 2025. Expert Rev Neurother. 2015;15:73-82. Erratum: Expert Rev Neurother. 2015;15:459.
3. National Alzheimer's Project Act. http://napa.alz.org/national-alzheimers-project-act-backgroun. Accessed 25 May 2016.
4. Schneider LS, Mangialasche F, Adreasen N, Feldman H, Giacobini E, Jones R, et al. Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014. J Intern Med. 2014;275:251-83.
5. Cummings JL, Morstorf T, Zhong K. Alzheimer's disease drug-development pipeline: few candidates, frequent failures. Alz Res Ther. 2014;6:37.
6. Schneider LS, Sano M. Current Alzheimer's disease clinical trials: methods and placebo outcomes. Alzheimers Dement. 2009;5:388-97.
7. Siemers E. Drug development in AD: point of view from the industry. J Prev Alz Dis. 2015;2:216-8.
8. Henley DB, Sundell KL, Sethuraman G, Dowsett SA, May PC. Safety profile of semagacestat, a gamm-secretase inhibitor: IDENTITY trial findings. Curr Med Res Opin. 2014;10:2021-32.
9. Sugino H, Watanabe A, Amada N, Yamamoto M, Ohgi Y, Kostic D, Sanchez R. Global trends in Alzheimer disease clinical development: increasing the probability of success. Clin Ther. 2015;37:1632-42.
10. Andrieu S, Coley N, Lovestone S, Aisen PS, Vellas B. Prevention of sporadic Alzheimer's disease: lessons learned from clinical trials and future directions. Lancet Neurol. 2015;14:926-44.
11. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:270-9.
12. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, DeKosky ST, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614-29. Erratum in: Lancet Neurol. 2014;13:757.
13. Scott TJ, O'Connor AC, Link AN, Beaulieu TJ. Economic analysis of opportunities to accelerate Alzheimer's disease research and development. New York Academy of Sciences. 2013. http://onlinelibrary.wiley.com/doi/10.1111/nyas.12417/epdf. Accessed 25 May 2016.
14. ALZFORUM therapeutics database. http://www.alzforum.org/therapeutics. Accessed 25 May 2016.
15. Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, Van der Flier WM. Alzheimer's disease. Lancet. 2016;388:505-17.
16. Hendrix JA, Bateman RJ, Brashear HR, Duggan C, Carrillo MC, Bain LJ, et al. Challenges, solutions, and recommendations for Alzheimer's disease combination therapy. Alzheimers Dement. 2016;12:623-30.
17. The Alzheimer's Prevention Registry. https://www.endalznow.org/. Accessed 25 May 2016.
18. The Dominantly Inherited Alzheimer Network (DIAN). https://dian-tu.wustl.edu/en/about-dian-trials-unit/. Accessed 25 May 2016.
19. The Brain Health Registry. http://www.brainhealthregistry.org/. Accessed 25 May 2016.
20. The Global Alzheimer's Platform Initiative. www.globalalzplatform.org. Accessed 25 May 2016.
21. Cumming J, Aisen P, Barton R, Bork J, Doody R, Dwyer J, et al. Re-engineering Alzheimer clinical trials: Global Alzheimer's Platform network. J Prev Alz Dis. 2016;3:114-20.
22. The Cleveland Clinic Healthy Brains Registry available at https://healthybrains.org/. Accessed 25 May 2016.
23. The Alzheimer's Disease Cooperative Study. http://www.adcs.org/. Accessed 25 May 2016.
24. The Join Dementia Research Initiative. https://www.joindementiaresearch.nihr.ac.uk. Accessed 25 May 2016.
25. Gillette-Guyonneta S, Vellas B. The Toulouse Gérontopôle Research Center: report of activities, 2007-2011. J Alzheimers Dis. 2012;28:721-32.
26. van der Flier WM, Pijnenburg YA, Prins N, Lemstra AW, Bouwman FH, Teunissen CE, et al. Optimizing patient care and research: the Amsterdam Dementia Cohort. J Alzheimers Dis. 2014;41:313-27.
27. Kornhuber J, Schmidtke K, Frolich L, Perneczky R, Wolf S, Hampel H, et al. Early and differential diagnosis of dementia and mild cognitive impairment: design and cohort baseline characteristics of the German Dementia Competence Network. Dement Geriatr Cogn Disord. 2009;27:404-17.
28. Zahodne LB, Manly JJ, MacKay-Brandt A, Stern Y. Cognitive declines precede and predict functional declines in aging and Alzheimer's disease. PLoS One. 2013;8:e73645.
29. Liu-Seifert H, Siemers E, Sundell K, Price K, Han B, Selzler K, et al. Cognitive and functional decline and their relationship in patients with mild Alzheimer's dementia. J Alz Dis. 2015;43:949-55.
30. Dubois B, Albert ML. Amnestic MCI or prodromal Alzheimer's disease? Lancet Neurol. 2004;3:246-8.
31. Sarazin M, Berr C, De Rotrou J, Fabrigoule C, Pasquier F, Legrain S, et al. Amnestic syndrome of the medial temporal type identifies prodromal AD: a longitudinal study. Neurology. 2007;69:1859-67.
32. Wagner M, Wolf S, Reischies FM, Daerr M, Wolfsgruber S, Jessen F, et al. Biomarker validation of a cued recall memory deficit in prodromal Alzheimer disease. Neurology. 2012;78:379-86.
33. Jekel K, Damian M, Wattmo C, Hausner L, Bullock R, Connelly PJ, et al. Mild cognitive impairment and deficits in instrumental activities of daily living: a systematic review. Alzheimers Res Ther. 2015;18:7-17.
34. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Draft guidance for industry - Alzheimer's disease: developing drugs for the treatment of early stage disease. Feb 2013. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM338287.pdf. Accessed 25 May 2016.
35. Donohue MC, Sperling RA, Salmon DP, Rentz DM, Raman R, Thomas RG, et al. Australian Imaging, Biomarkers, and Lifestyle Flagship Study of Ageing, Alzheimer's Disease Neuroimaging Initiative, Alzheimer's Disease Cooperative Study. The preclinical Alzheimer cognitive composite: measuring amyloid-related decline. JAMA Neurol. 2014;71:961-70.
36. Wessels AM, Siemers ER, Yu P, Andersen SW, Holdridge KC, Sims JR, et al. A combined measure of cognition and function for clinical trials: the integrated Alzheimer's disease rating scale. J Prev Alz Dis. 2015;2:227-41.
37. Wang J, Logovinsky V, Hendrix SB, Stanworth SH, Perdomo C, Xu L, et al. ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials. J Neurol Neurosurg Psychiatry. 2016;87:993-9.
38. Olsson B, Lautner R, Andreasson U, Öhrfelt A, Portelius E, Bjerke M, et al. CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15:673-84.
39. Siemers ER, Sundell KL, Carlson C, Case M, Sethuraman G, Liu-Seifert H, et al. Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer's disease patients. Alzheimers Dement. 2016;12:110-20.
40. Petersen RC, Aisen P, Boeve BF, Geda YE, Ivnik RJ, Knopman DS, et al. Criteria for mild cognitive impairment due to alzheimer's disease in the community. Ann Neurol. 2013;74:199-208.
41. Appleby BS, Nacopoulos D, Milano N, Zhong K, Cummings JL. A review: treatment of Alzheimer's disease discovered in repurposed agents. Dement Geriatr Cogn Disord. 2013;35:1-22.
42. Appleby BS, Cummings JL. Discovering new treatments for Alzheimer's disease by repurposing approved medications. Curr Top Med Chem. 2013;13:2306-27.
43. Cummings JL, Zhong K, Kinney JW, Heaney C, Moll-Tudla J, Joshi A, et al. Double-blind, placebo-controlled, proof-of-concept trial of bexarotene in moderate Alzheimer's disease. Alz Res Ther. 2016;8:4.
44. Sanchez PE, Zhu L, Verret L, Vossel KA, Orr AG, Cirrito JR, Devidze N, Ho K, Yu GQ, Palop JJ, Mucke L. Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model. Proc Natl Acad Sci U S A. 2012;109:E2895-903.
45. Cummings JL, Zhong K. Repackaging FDA-approved drugs for degenerative diseases: promises and challenges. Expert Rev Clin Pharmacol. 2014;7:161-5.
46. European Medicines Agency Committee for Medicinal Products for Human Use. Draft guideline on the clinical investigation of medicines for the treatment of Alzheimer's disease and other dementias. Jan 2016 (EMA/CHMP/539931/2014). http://www.ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2016/02/WC500200830.pdf. Accessed 25 May 2016.
47. CDER New Drug Review: 2015 Update. FDA/CMS Summit 2014. http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM477020.pdf slide 20. Accessed 25 May 2016.
48. Food US, Administration D. White Paper: FDA and accelerating the development of the new pharmaceutical therapies. 2015. http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm439082.htm. Accessed 25 May 2016.
49. Shea M, Ostermann L, Hohman R, Roberts S, Kozak M, Dull R, et al. Impact of breakthrough therapy designation on cancer drug development. Nature. 2016;15:152.
50. European Medicines Agency Committee for Medicinal Products for Human Use. Draft guideline on the scientific application and the practical arrangements necessary to implement the procedure for accelerated assessment pursuant to article 14(9) of regulation (EC) No 726/2004 7. Jul 2015 (EMA/CHMP/697051/2014-Rev). http://ec.europa.eu/health/files/committee/stamp/2015-10-stamp3/stamp-3-16-3b-guideline-on-accelerated-assessment-public-consultation.pdf. Accessed 25 May 2016.
51. Cummings JL, Morstorf T, Lee G. Alzheimer's drug development pipeline: 2016. Alzheimers Dement. 2016 (in press).
52. Liu Q, Waltz S, Woodruff G, Ouyang J, Israel MA, Herrera C, et al. Effect of potent-secretase modulator in human neurons derived from multiple presenilin 1-induced pluripotent stem cell mutant carriers. JAMA Neurol. 2014;71:1481-9.
53. Choi SH, Kim YH, Hebisch M, Sliwinski C, Lee S, D'Avanzo C, et al. A three-dimensional human neural cell culture model of Alzheimer's disease. Nature. 2014;515:274-8.
54. Innovative Medicines Initiative. http://www.imi.europa.eu/. Accessed 25 May 2016.
55. Prediction of cognitive properties of new drug candidates for neurodegenerative diseases in early clinical development. http://www.alzheimer-europe.org/EN/Research/PharmaCog. Accessed 25 May 2016.
56. European Medical Information Framework Platform http://www.emif.eu/. Accessed 25 May 2016.
57. European Prevention of Alzheimer's Dementia (EPAD) Initiative. http://ep-ad.org/. Accessed 25 May 2016.
58. Critical Path Institute. https://c-path.org/. Accessed 25 May 2016.
59. Romero K, Ito K, Rogers JA, Polhamus D, Qiu R, Stephenson D, et al. The future is now: model-based clinical trial design for Alzheimer's disease. Clin Pharmacol Ther. 2015;97:210-4.
60. Global Alzheimer's Association Interactive Network. http://www.gaain.org/. Accessed 25 May 2016.
61. Accelerating Medicines Partnership - Alzheimer's Disease. https://www.nia.nih.gov/alzheimers/amp-ad. Accessed 25 May 2016.
62. Tariot PN, Ho C, Langlois C, Reiman EM, Lopera F, Langbaum JB, et al. The Alzheimer's Prevention Initiative. Alzheimers Dement. 2014;10(4):247.
63. Toga AW, Foster I, Kesselman C, Madduri R, Chard K, Deutsch EW, et al. Big biomedical data as the key resource for discovery science. J Am Med Inform Assoc. 2015;22:1126-31.
64. Haas M, Stephenson D, Romero K, Gordon M, Zach N, Geerts H; Brain Health Modeling Initiative. Big data to smart data in AD: real-world examples of advanced modeling and simulation. Alzheimers Dement. 2016. [Epub ahead of print]. doi: 10.1016/j.jalz.2016.05.005.
65. Geerts H, Dacks PA, Devanarayan V, Haas M, Khachaturian Z, Gordon MF, Maudsley S, Romero K, Stephenson D; Brain Health Modeling Initiative (BHMI). From big data to smart data in Alzheimer's disease. The brain health modeling initiative to foster actionable knowledge. Alzheimers Dement. 2016. [Epub ahead of print]. doi: 10.1016/j.jalz.2016.04.008.
66. The Alzheimer's Drug Discovery Foundation https://www.alzdiscovery.org/. Accessed 25 May 2016.
67. The Cure Alzheimer's Fund. http://www.curealz.org. Accessed 25 May 2016.
68. Give To Cure. http://www.givetocure.org/. Accessed 25 May 2016.