{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T15:15:06Z","timestamp":1765552506534,"version":"3.48.0"},"reference-count":31,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer's Disease Reports"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fosgonimeton, a small-molecule positive modulator of the neurotrophic hepatocyte growth factor (HGF) system, was studied in participants with Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the efficacy and safety of fosgonimeton in AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LIFT-AD was a randomized, placebo-controlled, Phase 2\/3 trial (NCT04488419; 23Jun2020), the primary analysis (N\u2009=\u2009287) included participants with mild-to-moderate AD not receiving concomitant acetylcholinesterase inhibitors (AChEIs) randomized 1:1 to daily subcutaneous fosgonimeton 40\u2005mg or placebo. The primary endpoint, the Global Statistical Test (GST) score, combined ADAS-Cog11 and ADCS-ADL23. Secondary endpoints included ADAS-Cog11, ADCS-ADL23, and NfL. Exploratory endpoints included plasma biomarkers of AD. Safety included all dosed participants, including those receiving and not receiving AChEIs or randomized to fosgonimeton 70\u2005mg (N\u2009=\u2009549).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The trial did not achieve its primary or secondary endpoints; between-group difference in the least-square mean change (SE) from baseline to Week 26 in the GST score was \u22120.08 (0.10) (p\u2009=\u20090.70), \u22120.70 (0.77) (p\u2009=\u20090.35) in ADAS-Cog11, and +0.67 (0.92) (p\u2009=\u20090.61) in ADCS-ADL23. This showed small differences favoring fosgonimeton versus placebo. Nominally significant changes in plasma biomarkers were observed in p-\u03c4217 only. Fosgonimeton had an acceptable safety profile. Serious AEs were balanced between groups (4.2% fosgonimeton, 6.9% placebo). More participants in the fosgonimeton group (14.2%) discontinued due to AEs versus placebo (4.6%), mostly from injection site reactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Fosgonimeton did not significantly improve ADAS-Cog11 or ADCS-ADL23 versus placebo. However, the consistently observed non-significant improvements favoring fosgonimeton suggests potentially relevant biological activity with fosgonimeton and that positive modulation of HGF signaling may impact components of the pathophysiologic processes of neurodegenerative diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/25424823251405817","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T14:52:21Z","timestamp":1765551141000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fosgonimeton in mild-to-moderate Alzheimer's disease"],"prefix":"10.1177","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0166-1738","authenticated-orcid":false,"given":"Anton P","family":"Porsteinsson","sequence":"first","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8139-3309","authenticated-orcid":false,"given":"Marwan","family":"Sabbagh","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute, St Joseph's Hospital and Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-8032","authenticated-orcid":false,"given":"Pierre N","family":"Tariot","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute and University of Arizona College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1261-7035","authenticated-orcid":false,"given":"Kevin J","family":"Church","sequence":"additional","affiliation":[{"name":"Athira Pharma, Inc."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5127-2129","authenticated-orcid":false,"given":"Javier","family":"San Martin","sequence":"additional","affiliation":[{"name":"Athira Pharma, Inc."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4030-6790","authenticated-orcid":false,"given":"Kai-Bin C","family":"Ooi","sequence":"additional","affiliation":[{"name":"Athira Pharma, Inc."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7098-0492","authenticated-orcid":false,"given":"Simon","family":"Daggett","sequence":"additional","affiliation":[{"name":"Athira Pharma, Inc."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6890-196X","authenticated-orcid":false,"given":"Michael D","family":"Hale","sequence":"additional","affiliation":[{"name":"Athira Pharma, Inc."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Holub","sequence":"additional","affiliation":[{"name":"Neurological Associates Albany, Albany, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6311-0157","authenticated-orcid":false,"given":"Hans J","family":"Moebius","sequence":"additional","affiliation":[{"name":"Senior Scientific Advisor to Athira Pharma, Inc., Bothell, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0333-5"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-019-0524-y"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-022-01325-5"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101580"},{"key":"e_1_3_5_6_2","article-title":"The economic and societal burden of Alzheimer disease: managed care considerations","volume":"28","author":"Skaria AP","year":"2022","unstructured":"Skaria AP. 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