Abstract Details

Title Efficacy and Safety of Intravenous Solanezumab in Patients with Mild to Moderate Alzheimer's Disease: Results of Two Phase 3 Studies

Topic Aging and Dementia

Presentation(s) S24 - (-)

Poster/Presentation
Number 006

Objective

Background Solanezumab, a humanized monoclonal antibody that binds to the mid-domain of soluble monomeric forms of amyloid beta peptide was developed for the treatment of Alzheimer's disease (AD).

Design/Methods Subjects with mild to moderate stage AD (baseline Mini-Mental State Examination scores 16-26) were enrolled in 2 Phase 3 trials (EXPEDITION and EXPEDITION2.) Participants were randomized to 400 mg solanezumab IV or placebo once every 4 weeks for 80 weeks. Cognition was assessed using the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog); daily functioning, by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) inventory. Additional measures of efficacy and safety were also assessed. Data analyses were conducted according to the Lilly prespecified statistical analysis plan.

Results A total of 2052 participants were randomized. For the EXPEDITION study, the primary outcome measures were the ADAS-Cog11 and ADCS-ADL. No statistically significant differences were seen between the solanezumab-treated group and placebo group for the overall mild to moderate population for either measure (p=0.312 and 0.931, respectively.) However, a prespecified secondary analysis revealed a statistically significant difference favoring the solanezumab group in cognition (ADAS-Cog14, p=0.006) for the mild subpopulation. Consequently, the primary outcome measure for EXPEDITION2 was revised to the ADAS-Cog14 for the mild subpopulation prior to database lock. However, this did not meet statistical significance (p=0.120.) Statistically significant differences favoring solanezumab for cognition in the pooled mild subpopulation and the overall population for the two studies were seen, as well as for instrumental ADLs in the mild subpopulation of EXPEDITION2 and the pooled mild subpopulation for the two studies. Solanezumab was generally safe and well tolerated.

Conclusions These Phase 3 results will provide important efficacy and safety data for solanezumab, relative to its use in patients with mild and moderate AD; and will help to advance the understanding of the amyloid hypothesis.

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 $100,000-$499,999 for serving as a Consultant for Cogstate Ltd. 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. The institution of Dr. Siemers has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for US Green Valley Pharmaceuticals, Inc. Dr. Siemers has stock in Acumen Pharmaceuticals. Dr. Siemers has 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. Dr. Siemers has a non-compensated relationship as a Board of Directors with Bright Focus Foundation that is relevant to AAN interests or activities. Dr. Siemers has a non-compensated relationship as a Board of Directors with Huntington Study Group that is relevant to AAN interests or activities.
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
	No disclosure on file
Yun-Fei Chen, PhD	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
Eric Klawiter, MD, FAAN (Massachusetts General Hospital)	Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Galen/Atlantica. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Banner Life Sciences. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Klawiter has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for OM1. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. The institution of Dr. Klawiter has received research support from Biogen. The institution of Dr. Klawiter has received research support from Abbvie. The institution of Dr. Klawiter has received research support from Genentech.

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