Abstract Details

Title Effects of Intravenous Solanezumab 400 mg q 4 Weeks vs. Placebo on Biomarkers in Patients with Mild to Moderate Alzheimer's Disease: Results of Two Phase 3 Studies

Topic Aging and Dementia

Presentation(s) P01 - (-)

Poster/Presentation
Number 011

Objective

Background Solanezumab is a humanized monoclonal antibody developed for the treatment of Alzheimer's disease (AD). It binds to the mid-domain of soluble monomeric forms of amyloid beta (A?) peptide but not to deposited amyloid plaques.

Design/Methods Subjects with mild to moderate stage AD (as determined using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria and baseline Mini-Mental State Examination scores of 16-26) were enrolled in two Phase 3 trials (EXPEDITION and EXPEDITION2) between May 2009 and December 2010. Participants were randomized to 400 mg solanezumab IV or placebo once every 4 weeks for 80 weeks. Cognition and daily functioning as well as several additional measures of efficacy and safety were assessed. Plasma was repeatedly collected from all subjects. Cerebrospinal fluid (CSF) was obtained in a subpopulation by lumbar puncture at study baseline and endpoint. Plasma and CSF total A?1-40 and A?1-42 and CSF free A?1-40, free A?1-42, total tau and P-tau181 were determined using validated immunoassays. All participants underwent structural and volumetric magnetic resonance imaging at baseline and at Weeks 12, 28, 52 and 80. A subset of participants underwent florbetapir PET imaging. Analyses of the individual studies were performed, as well as pre-specified pooled analyses of the overall and mild populations.

Results A total of 2052 participants were randomized. Solanezumab administration was associated with target engagement and evidence of effect on plaque, but effects on downstream markers of pathology were not demonstrated.

Conclusions Solanezumab target engagement is associated with alteration of amyloid biology. There was a lack of apparent effect on markers of neurodegeneration. The overall findings lend support for the amyloid cascade hypothesis and suggest that various aspects of the cascade are viable targets for treatment of Alzheimer's disease.

Authors/Disclosures
Ann M. Hake, MD, FAAN (Eli Lilly & Co.) PRESENTER	No disclosure on file
Eric R. Siemers, MD (Siemers Integration LLC)	Dr. Siemers has received personal compensation for serving as an employee of Acumen Pharmaceuticals. The institution of Dr. Siemers has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for Vaccinex Pharmceuticals. The institution of Dr. Siemers has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for Gates Ventures LLC. Dr. Siemers has or had stock in Acumen Pharmaceuticals.Dr. Siemers has or had stock in Ell Lilly and Company.Dr. Siemers has received personal compensation in the range of $0-$499 for serving as a study section reviewer with National Institutes of Health. Dr. Siemers has a non-compensated relationship as a Volunteer with Alzheimer's Association that is relevant to AAN interests or activities.
	No disclosure on file
Christopher Carlson, PhD	No disclosure on file
Wahiba B. Estergard, PharmD	No disclosure on file
Karen Sundell (Eli Lilly and Company)	Karen Sundell has received personal compensation for serving as an employee of Acumen Pharmaceuticals . Karen Sundell has stock in Acumen Pharmaceuticals .
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Benjamin M. Greenberg, MD, FAAN (UT Southwestern Medical Center)	Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Greenberg has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Greenberg has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Clene. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IQVIA. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abcuro. Dr. Greenberg has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Siegel Rare Neuroimmune Association. Dr. Greenberg has or had stock in GenrAb.Dr. Greenberg has or had stock in Clene.Dr. Greenberg has received intellectual property interests from a discovery or technology relating to health care. Dr. Greenberg has received publishing royalties from a publication relating to health care.
	No disclosure on file
Yun-Fei Chen, PhD	No disclosure on file
Mark A. Mintun, MD	Dr. Mintun has received personal compensation for serving as an employee of Eli Lilly & Co.
Michael J. Pontecorvo, PhD (Avid Radiopharmaceuticals)	Dr. Pontecorvo has received personal compensation for serving as an employee of Eli Lilly. Dr. Pontecorvo has stock in Eli Lilly.
	No disclosure on file
Robert A. Dean	Robert A. Dean has received personal compensation for serving as an employee of Acumen Pharmaceutics. Robert A. Dean has received personal compensation for serving as an employee of Gates Ventures. Robert A. Dean has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Robert A Dean Consulting, LLC. Robert A. Dean has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acumen.
	No disclosure on file
	No disclosure on file
Richard Mohs, PhD	No disclosure on file

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