{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T09:35:55Z","timestamp":1776504955308,"version":"3.51.2"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T00:00:00Z","timestamp":1589241600000},"content-version":"vor","delay-in-days":132,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The recent failure of several late\u2010stage Alzheimer's disease (AD) clinical trials focused on amyloid beta (A\u03b2) highlights the challenges of finding effective disease\u2010modifying therapeutics. Despite major advances in our understanding of the genetic risk factors of disease and the development of clinical biomarkers, and that not all A\u03b2\u2010based approaches are equivalent, these failures may engender skepticism regarding the value of the AD pipeline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate these concerns, we compiled a database of current Phase 2 and 3 trials based on disease\u2010modifying targets through a query of the National Institutes of Health's ClinicalTrials.gov. We then assessed the financial value of the pipeline. Financial modeling utilized risk\u2010adjusted net present value (rNPV) measurements and included sensitivity analyses to help inform the drug development process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Results indicate that the preponderance of current Phase 3 trials were indeed targeting A\u03b2, with only 15% addressing other targets. In contrast, the pipeline of Phase 2 trials was more diverse. The estimated rNPV of Phase 2 and 3 therapeutics was estimated to be $338 billion over 10 years. This figure increased to a theoretical cumulative value of $788 billion when incorporating the assumption that diagnostics will be developed to identify individuals at high risk for developing AD. Results from model sensitivity analyses showed that speed of market penetration and patient access contributed the most weight to financial value. In contrast, decreasing drug development costs had minimal impact on rNPV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings argue in favor of conducting thorough biomarker\u2010driven Phase 2 proof of concept studies to avoid prematurely advancing assets into Phase 3. Insights from these analyses are also discussed in the context of the financial ecosystem needed to maintain a healthy AD pipeline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.12009","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T14:21:50Z","timestamp":1589293310000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["On the horizon\u2014the value and promise of the global pipeline of Alzheimer's disease therapeutics"],"prefix":"10.1002","volume":"6","author":[{"given":"Michael A.","family":"Cole","sequence":"first","affiliation":[{"name":"Clinical Science Program University of California Berkeley  Berkeley California USA"},{"name":"Global Neurohealth Ventures  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy R.","family":"Seabrook","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson Innovation  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.01.010"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1311"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21434"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nic.2005.09.008"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv404"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2583"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20412"},{"key":"e_1_2_6_10_1","first-page":"2","article-title":"Moving away from amyloid beta to move on in Alzheimer research","volume":"7","author":"Moreno\u2010Trevino MG","year":"2015","journal-title":"Front Aging Neurosci"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/mi.7.5.8"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr1611785"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.14668"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0901-813"},{"key":"e_1_2_6_15_1","unstructured":"PrinceM WimoA GuerchetM AliG\u2010C WuY\u2010T PrinaM.World Alzheimer Report 2015: the Global impact of dementia an analysis of prevalence incidence cost and trends.2015."},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.03.001"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.6669"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.2445"},{"key":"e_1_2_6_19_1","unstructured":"LangrethR MigliozziB GokhaleK The U.S. pays a lot more for top drugs than other countries.2015[cited November 4 2019]; 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