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N Engl J Med. 2018 Jan 25;378(4):321-330. doi: 10.1056/NEJMoa1705971.

Trial of Solanezumab for Mild Dementia Due to Alzheimer's Disease.

Author information

1
From the Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York (L.S.H.); Gérontopôle, Centre Hospitalier Universitaire Toulouse, Unité Mixte de Recherche INSERM Unité 1027 Université Toulouse III-Paul Sabatier, Toulouse, France (B.V.); Austin Health Continuing Care Clinical Service Unit, Heidelberg, and the University of Melbourne, Melbourne, VIC - both in Australia (M.W.); Fundació ACE, Alzheimer Research Center and Memory Clinic, Institut Català de Neurociències Aplicades, Barcelona (M. Boada); Kingshill Research Centre, Victoria Hospital, Swindon, United Kingdom (R.B.); the Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada (M. Borrie); Clinic for Medicine of the Elderly, Diakovere Henriettenstift, Hannover, Germany (K.H.); Karolinska Institutet Alzheimer's Disease Research Center and Clinical Trial Unit, Geriatric Clinic, Karolinska University Hospital, Huddinge, Sweden (N.A.); the Department of Pathophysiology and Transplantation, Neurology Unit, Dino Ferrari Center, University of Milan, Fondazione Ca' Granda, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico, Milan (E. Scarpini); Eli Lilly (H.L.-S., M.C., A.H., K.S., V.P.H., C.C., R.K., M.M., R.D., K.J.S., E. Siemers) and the Department of Pathology and Laboratory Medicine, Indiana University School of Medicine (R.A.D.) - both in Indianapolis; and Avid Radiopharmaceuticals, Philadelphia (M.M.).

Abstract

BACKGROUND:

Alzheimer's disease is characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. The humanized monoclonal antibody solanezumab was designed to increase the clearance from the brain of soluble Aβ, peptides that may lead to toxic effects in the synapses and precede the deposition of fibrillary amyloid.

METHODS:

We conducted a double-blind, placebo-controlled, phase 3 trial involving patients with mild dementia due to Alzheimer's disease, defined as a Mini-Mental State Examination (MMSE) score of 20 to 26 (on a scale from 0 to 30, with higher scores indicating better cognition) and with amyloid deposition shown by means of florbetapir positron-emission tomography or Aβ1-42 measurements in cerebrospinal fluid. Patients were randomly assigned to receive solanezumab at a dose of 400 mg or placebo intravenously every 4 weeks for 76 weeks. The primary outcome was the change from baseline to week 80 in the score on the 14-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog14; scores range from 0 to 90, with higher scores indicating greater cognitive impairment).

RESULTS:

A total of 2129 patients were enrolled, of whom 1057 were assigned to receive solanezumab and 1072 to receive placebo. The mean change from baseline in the ADAS-cog14 score was 6.65 in the solanezumab group and 7.44 in the placebo group, with no significant between-group difference at week 80 (difference, -0.80; 95% confidence interval, -1.73 to 0.14; P=0.10). As a result of the failure to reach significance with regard to the primary outcome in the prespecified hierarchical analysis, the secondary outcomes were considered to be descriptive and are reported without significance testing. The change from baseline in the MMSE score was -3.17 in the solanezumab group and -3.66 in the placebo group. Adverse cerebral edema or effusion lesions that were observed on magnetic resonance imaging after randomization occurred in 1 patient in the solanezumab group and in 2 in the placebo group.

CONCLUSIONS:

Solanezumab at a dose of 400 mg administered every 4 weeks in patients with mild Alzheimer's disease did not significantly affect cognitive decline. (Funded by Eli Lilly; EXPEDITION3 ClinicalTrials.gov number, NCT01900665 .).

PMID:
29365294
DOI:
10.1056/NEJMoa1705971
[Indexed for MEDLINE]
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