Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer's disease patients
Eric Siemers,Karen Sundell,Christopher Carlson,Michael Case,Gopalan Sethuraman,Hong Liu-Seifert,Sherie A. Dowsett,Michael J. Pontecorvo,Robert A. Dean,Ronald B. DeMattos +9 more
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TLDR
Two identically designed placebo‐controlled phase 3 studies assessing effects of solanezumab, an antiamyloid monoclonal antibody binding soluble amyloid‐β peptide, on cognitive and functional decline over 80 weeks in patients with mild‐to‐moderate Alzheimer's disease (AD).Abstract:
Introduction EXPEDITION and EXPEDITION2 were identically designed placebo-controlled phase 3 studies assessing effects of solanezumab, an antiamyloid monoclonal antibody binding soluble amyloid-β peptide, on cognitive and functional decline over 80 weeks in patients with mild-to-moderate Alzheimer's disease (AD). Primary findings for both studies have been published. Methods Secondary analyses of efficacy, biomarker, and safety endpoints in the pooled (EXPEDTION + EXPEDITION2) mild AD population were performed. Results In the mild AD population, less cognitive and functional decline was observed with solanezumab (n = 659) versus placebo (n = 663), measured by Alzheimer's Disease Assessment Scale Cognitive subscale, Mini-Mental State Examination, and Alzheimer's Disease Cooperative Study–Activities of Daily Living functional scale Instrumental ADLs. Baseline-to-endpoint changes did not differ between treatment groups for Alzheimer's Disease Cooperative Study–Activities of Daily Living functional scale, basic items of the ADCS-ADL, and Clinical Dementia Rating Sum of Boxes. Plasma/cerebrospinal fluid biomarker findings indicated target engagement by solanezumab. Solanezumab demonstrated acceptable safety. Efficacy findings for the moderate AD population are also provided. Discussion These findings describe solanezumab effects on efficacy/safety measures in a mild AD population. Another phase 3 study, EXPEDITION3, will investigate solanezumab's effects in a mild AD population.read more
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Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease
Lawrence S. Honig,Bruno Vellas,Michael M Woodward,Mercè Boada,Roger Bullock,Michael Borrie,Klaus Hager,Niels Andreasen,Elio Scarpini,Elio Scarpini,Hong Liu-Seifert,Michael Case,Robert A. Dean,Ann Marie Hake,Karen Sundell,Vicki Poole Hoffmann,Christopher Carlson,Rashna Khanna,Mark A. Mintun,Mark A. Mintun,Ronald B. DeMattos,Katherine J. Selzler,Eric Siemers +22 more
TL;DR: Solanezumab at a dose of 400 mg administered every 4 weeks in patients with mild Alzheimer's disease did not significantly affect cognitive decline and the secondary outcomes were considered to be descriptive and are reported without significance testing.
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Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease
Stephen Salloway,Reisa A. Sperling,Nick C. Fox,Kaj Blennow,William E. Klunk,Murray A. Raskind,Marwan N. Sabbagh,Lawrence S. Honig,Anton P. Porsteinsson,Steven H. Ferris,Marcel Reichert,Nzeera Ketter,Bijan Nejadnik,Volkmar Guenzler,Maja Miloslavsky,Daniel Wang,Yuan Lu,Julia Lull,Iulia Cristina Tudor,Enchi Liu,Michael Grundman,Eric C. Yuen,Ronald Black,H. Robert Brashear +23 more
TL;DR: Bapineuzumab did not improve clinical outcomes in patients with Alzheimer's disease, despite treatment differences in biomarkers observed in APOE ε4 carriers.
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