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Safety and Changes in Plasma and Cerebrospinal Fluid Amyloid β After a Single Administration of an Amyloid β Monoclonal Antibody in Subjects With Alzheimer Disease

Siemers, Eric R. MD*; Friedrich, Stuart PhD*; Dean, Robert A. MD, PhD*; Gonzales, Celedon R. MS*; Farlow, Martin R. MD; Paul, Steven M. MD*; DeMattos, Ronald B. PhD*

doi: 10.1097/WNF.0b013e3181cb577a
Original Articles
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Objectives: Active and passive immunization strategies have been suggested as possible options for the treatment of Alzheimer disease (AD). LY2062430 (solanezumab) is a humanized monoclonal antibody being studied as a putative disease-modifying treatment of AD.

Methods: Patients with mild to moderate AD were screened and selected for inclusion. Initial screening was performed for 54 subjects, and 29 of these underwent additional screening; after this second screening, a total of 19 subjects were included. Single doses of solanezumab using 0.5, 1.5, 4.0, and 10.0 mg/kg were administered. Safety assessments included gadolinium-enhanced magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) analyses at baseline and 21 days after dosing. Plasma and CSF concentrations of solanezumab and amyloid β (Aβ) and cognitive evaluations were obtained.

Results: Administration of solanezumab was generally well tolerated except that mild self-limited symptoms consistent with infusion reactions occurred for 2 of 4 subjects given 10 mg/kg. No evidence of meningoencephalitis, microhemorrhage, or vasogenic edema was present based on magnetic resonance image and CSF analyses. A substantial dose-dependent increase in total (bound plus unbound) Aβ was demonstrated in plasma; CSF total Aβ also increased. No changes in cognitive scores occurred.

Conclusions: A single dose of solanezumab was generally well tolerated, although infusion reactions similar to those seen with administration of other proteins may occur with higher doses. A dose-dependent change in plasma and CSF Aβ was observed, although changes in cognitive scores were not noted. Further studies of solanezumab for the treatment of AD are warranted.

From the *Eli Lilly and Company, Lilly Research Laboratories; and †Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana.

Address correspondence and reprint requests to Eric Siemers, MD, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285; E-mail: esiemers@lilly.com

This clinical trial was conducted by Eli Lilly and Company.

© 2010 Lippincott Williams & Wilkins, Inc.