Safety and biomarker effects of solanezumab in patients with Alzheimer's disease

Martin Farlow, Steven E. Arnold, Christopher H. Van Dyck, Paul S. Aisen, B. Joy Snider, Anton P. Porsteinsson, Stuart Friedrich, Robert A. Dean, Celedon Gonzales, Gopalan Sethuraman, Ronald B. Demattos, Richard Mohs, Steven M. Paul, Eric R. Siemers

Research output: Contribution to journalArticle

180 Scopus citations

Abstract

Objectives: To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of 12 weekly infusions of solanezumab, an anti-β-amyloid (Aβ) antibody, in patients with mild-to-moderate Alzheimer's disease. Cognitive measures were also obtained. Methods: In this phase 2, randomized, double-blind, placebo-controlled clinical trial, 52 patients with Alzheimer's disease received placebo or antibody (100 mg every 4 weeks, 100 mg weekly, 400 mg every 4 weeks, or 400 mg weekly) for 12 weeks. Safety and biomarker evaluations continued until 1 year after randomization. Both magnetic resonance imaging and cerebrospinal fluid (CSF) examinations were conducted at baseline and after the active treatment period. The Aβ concentrations were measured in plasma and CSF, and the Alzheimer's Disease Assessment Scale-cognitive portion was administered. Results: Clinical laboratory values, CSF cell counts, and magnetic resonance imaging scans were unchanged by treatment, and no adverse events could be clearly related to antibody administration. Total (bound to antibody and unbound) Aβ 1-40 and Aβ 1-42 in plasma increased in a dose-dependent manner. Antibody treatment similarly increased total Aβ 1-40 and Aβ 1-42 in CSF. For patients taking 400 mg weekly, antibody treatment decreased unbound Aβ 1-40 in CSF (P <.01), but increased unbound Aβ 1-42 in CSF in a dose-dependent manner. The Alzheimer's Disease Assessment Scale-cognitive portion was unchanged after the 12-week antibody administration. Conclusions: Antibody administration was well tolerated with doses up to 400 mg weekly. The dose-dependent increase in unbound CSF Aβ 1-42 suggests that this antibody may shift Aβ equilibria sufficiently to mobilize Aβ 1-42 from amyloid plaques.

Original languageEnglish (US)
Pages (from-to)261-271
Number of pages11
JournalAlzheimer's and Dementia
Volume8
Issue number4
DOIs
StatePublished - Jul 1 2012

Keywords

  • β-amyloid
  • Aβ monoclonal antibody
  • Alzheimer's disease
  • Cerebrospinal fluid immunotherapy
  • LY2062430
  • Solanezumab

ASJC Scopus subject areas

  • Health Policy
  • Epidemiology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience
  • Clinical Neurology

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    Farlow, M., Arnold, S. E., Van Dyck, C. H., Aisen, P. S., Snider, B. J., Porsteinsson, A. P., Friedrich, S., Dean, R. A., Gonzales, C., Sethuraman, G., Demattos, R. B., Mohs, R., Paul, S. M., & Siemers, E. R. (2012). Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimer's and Dementia, 8(4), 261-271. https://doi.org/10.1016/j.jalz.2011.09.224