Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease

• Published in: The New England journal of medicine Vol. 370; no. 4; pp. 311 - 321
• Main Authors: Doody, Rachelle S, Thomas, Ronald G, Farlow, Martin, Iwatsubo, Takeshi, Vellas, Bruno, Joffe, Steven, Kieburtz, Karl, Raman, Rema, Sun, Xiaoying, Aisen, Paul S, Siemers, Eric, Liu-Seifert, Hong, Mohs, Richard
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 23.01.2014
• Subjects: Activities of Daily Living; Adult and adolescent clinical studies; Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - drug therapy; Alzheimer's disease; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - cerebrospinal fluid; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Apolipoproteins E - blood; Apolipoproteins E - genetics; Biological and medical sciences; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Clinical trials; Cognition - drug effects; Cognitive ability; Data processing; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Double-Blind Method; Drug therapy; Edema; Female; General aspects; Gliosis; Hemorrhage; Humans; Intention to Treat Analysis; Male; Medical sciences; Monoclonal antibodies; Neurodegenerative diseases; Neurofibrillary tangles; Neuroimaging; Neurology; Neuropsychological Tests; Older people; Organic mental disorders. Neuropsychology; Plaques; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Quality of life; Severity of Illness Index; tau Proteins - cerebrospinal fluid; Treatment Failure; Medicine; Nervous system diseases; Degenerative disease; Alzheimer disease; Central nervous system disease; Cerebral disorder
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1312889

In two phase 3 placebo-controlled, randomized trials in 1012 and 1040 patients with mild-to-moderate Alzheimer's disease, solanezumab, a humanized monoclonal antibody that preferentially binds soluble forms of amyloid, did not improve cognition or functional status. Alzheimer's disease is associated with the accumulation of aggregated amyloid-beta (Aβ) peptide in the cerebral cortex and hippocampus. One approach to reducing brain amyloid involves increasing the clearance of Aβ by means of prolonged treatment with monoclonal antibodies directed against this peptide. In preclinical studies, a murine antibody that targeted the central domain of Aβ and was selective for soluble forms slowed Aβ deposition in a transgenic mouse model 1 ; in another transgenic murine model, Aβ–antibody complexes were present in the cerebrospinal fluid (CSF) and plasma, and behavioral deficits were reversed without a decrease in amyloid plaques, as assessed by . . .