Abstract Details

Title The Alzheimer Prevention Initiative Generation Program: Evaluation of CNP520 in Preclinical Alzheimer's Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-005

Objective

Evaluate the efficacy, safety and tolerability of CNP520, an oral Beta-site-APP cleaving enzyme-1 (BACE-1) inhibitor, compared to placebo, in people at risk for the onset of clinical symptoms of AD.

Background The lack of efficacy of BACE inhibitors in symptomatic AD patients supports the evaluation of this mechanism earlier in the disease process.

Design/Methods The Generation Program comprises two pivotal (phase 2/3) randomized, double-blind, placebo-controlled, parallel group studies with similar design to assess the efficacy and safety of CNP520 in a cognitively unimpaired population at increased risk for developing AD based on their age and APOE4 genotype. Generation Study 1 evaluates CNP520 and CAD106 (an active amyloid immunotherapy), in separate cohorts, in participants who are homozygous (HM) for APOE4. Generation Study 2 evaluates CNP520 in subjects who carry 1 or 2 copies of the APOE4 gene, with heterozygotes (HTs) requiring elevated brain amyloid as measured by amyloid PET imaging or Aβ levels in cerebrospinal fluid. Approximately 3500 participants will be randomized across studies. Participants will be treated for 60-96 months.

Results

Efficacy will be evaluated by two primary endpoints: (i) time to event (TTE), with event defined as diagnosis of MCI due to AD or dementia due to AD, and (ii) changes from baseline in APCC test score, a cognitive battery developed to track cognitive decline in individuals at risk to progress to clinical stages of AD. CDR-SOB, RBANS, and ECog, are included as secondary endpoints. The program will also investigate the effects of CNP520 on the underlying AD pathology assessed by a broad panel of biomarkers.

Conclusions

The Generation Program is designed to provide efficacy, safety and tolerability data for CNP520 compared to placebo in people at risk for the onset of clinical symptoms of AD. Generation Study 1 and Generation Study 2 are currently enrolling.

Authors/Disclosures
PRESENTER	No disclosure on file
Cristina Lopez Lopez, MD, PhD (Novartis)	No disclosure on file
Pierre Tariot (Banner Alzheimer's Institute)	Pierre Tariot has received personal compensation for serving as an employee of Banner Alzheimer's Institute. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Axsome. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for WebMD. Pierre Tariot has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arcadia. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BioXcel. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cortexyme. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Pierre Tariot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for eNOVA. Pierre Tariot has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Pierre Tariot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Syneos. Pierre Tariot has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Fonda Liu	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Jessica Langbaum, PhD	Dr. Langbaum has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Langbaum has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Denovo Biopharma. Dr. Langbaum has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Langbaum has received research support from Eli Lilly.
Vissia Viglietta, MD	No disclosure on file
Eric M. Reiman, MD (Banner Alzheimer's Institute)	Dr. Reiman has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Denali, Green Valley, Zinfandel, and Takeda. Dr. Reiman has received stock or an ownership interest from Alkahest, Alzheon, Aural Analytics, Denali, and United Neuroscience.. Dr. Reiman has received intellectual property interests from a discovery or technology relating to health care. Dr. Reiman has received personal compensation in the range of $500-$4,999 for serving as a Member, National Advisory Council on Aging (NACA) with NIA.
Ana Graf, MD (Novartis)	No disclosure on file

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