Baseline Characteristics from Evoke and Evoke+: Two Phase 3 Randomized Placebo-controlled Trials of Oral Semaglutide in Patients with Early Alzheimer’s Disease (P11-9.013)

We report the preliminary baseline characteristics in the ongoing phase 3 evoke and evoke+ trials investigating the safety and efficacy of oral semaglutide for early AD. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is approved for use in type 2 diabetes (T2D) or obesity. evoke (NCT04777396) and evoke+ (NCT04777409) are multicenter, randomized, double-blind, placebo-controlled trials. Eligible individuals were 55-85 years, amyloid-positive, with mild cognitive impairment (MCI) due to AD and Mini-Mental State Examination (MMSE) score ≥22. Participants were randomized 1:1 to once-daily oral semaglutide 14 mg (titrated from 3 mg for the initial 4 weeks and 7 mg for the following 4 weeks) or placebo plus standard of care for 156 weeks (104 weeks + 52-week extension). The primary endpoint is change in the CDR - Sum of Boxes (CDR-SB). Baseline characteristics of enrolled patients were compiled after completion of enrollment on September 8, 2023. Trials are ongoing, data may be subject to minor changes until database lock. evoke and evoke+ enrolled 1,855 and 1,835 participants each; data from 118 randomized participants from evoke+ are not included here. Mean (SD) age was 71.8 (7.1) and 72.6 (7.1) years; 53.0% and 51.8% of participants were female; most participants (76.6%) were White; 59.7% and 54.5% were in receipt of AD medication. Mean (SD) CDR-SB score was 3.7 (1.5) and 3.7 (1.6); ADCS-ADL-MCI score was 39.4 (7.3) and 38.9 (7.5); 72.5% and 68.7% of participants had a CDR global score of 0.5. evoke and evoke+ are the first large-scale phase 3 trials to investigate the disease-modifying potential of semaglutide in early AD. Both studies recruited a very similar population. Disclosure: Dr. Scheltens has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NOVO NOrdisk. Dr. Atri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Atri has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Prothena. Dr. Atri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Atri has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eisai. Dr. Atri has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novo Nordisk. Dr. Atri has received personal compensation in the range of $0-$499 for serving as a Consultant for Qynapse. Dr. Atri has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Atri has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Atri has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novo Nordisk. Dr. Atri has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Atri has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lunbeck. The institution of Dr. Atri has received research support from National Institute of Aging (NIA). The institution of Dr. Atri has received research support from AZ Department of Health Services. The institution of Dr. Atri has received research support from Gates Ventures. The institution of Dr. Atri has received research support from Multiple companies, universities & consortia for contracted clinical trials to institution. The institution of Dr. Atri has received research support from Washington University in St. Louis. Dr. Atri has received publishing royalties from a publication relating to health care. The institution of Dr. Feldman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead Pharmaceuticals. The institution of Dr. Feldman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk. The institution of Dr. Feldman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen Research & Development LLC. The institution of Dr. Feldman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Banner/API. The institution of Dr. Feldman has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tau Consortium. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from Vivoryon Therapeutics. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from LuMind Foundation. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from Biohaven Pharmaceuticals. The institution of Dr. Feldman has received research support from UC San Diego School of Medicine Brain Health Support Program & Sanford Institute for Empathy and Compassion. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. Dr. Feldman has received intellectual property interests from a discovery or technology relating to health care. Dr. Feldman has a non-compensated relationship as a Medical Advisory Council with Association for Frontotemporal Degeneration (AFTD) that is relevant to AAN interests or activities. Dr. Feldman has a non-compensated relationship as a International Scientific Advisory Board with Translating Research in Elder Care (TREC) that is relevant to AAN interests or activities. Prof. Hansson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Prof. Hansson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Prof. Knop has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novo Nordisk. Prof. Knop has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Prof. Knop has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Prof. Knop has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zucara. Prof. Knop has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AstraZeneca. Prof. Knop has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novo Nordisk. Prof. Knop has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Prof. Knop has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ShouTi. Prof. Knop has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zucara. Prof. Knop has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novo Nordisk. Prof. Knop has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Eli Lilly. Prof. Knop has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZeneca. Prof. Knop has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanifi. Prof. Knop has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Boehringer Ingelheim. Prof. Knop has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for European Journal of Endocrinology. Prof. Knop has stock in Antag Therapeutics. The institution of Prof. Knop has received research support from Novo Nordisk. The institution of Prof. Knop has received research support from Zealand Pharma. Prof. Knop has received intellectual property interests from a discovery or technology relating to health care. Prof. Knop has received personal compensation in the range of $5,000-$9,999 for serving as a Scientific Steering Committee member on EVOKE / EVOKE+ with Novo Nordisk . Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for Avenir. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen Idec. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for BioXcel. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for CogRx. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for Eisai. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for Genentech. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for F. Hoffman LaRoche. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for Minerva Neuroscience. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for NovoNordisk. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for Pfizer. Dr. Sano has received personal compensation in the range of $0-$499 for serving as a Consultant for vTv Therapeutics. Dr. Sano has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Syneos. Dr. Sano has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Alzheimer's Association. Dr. Sano has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for International Psychogeriatric Association. Mr. Dethlefsen has received personal compensation for serving as an employee of Novo Nordisk. Mr. Dethlefsen has stock in Novo Nordisk. Dr. Johannsen has received personal compensation for serving as an employee of Novo Nordisk. Dr. Johannsen has stock in Novo Nordisk. Dr. Leon has received personal compensation for serving as an employee of Novo Nordisk. Dr. Leon has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lexeo. Dr. Leon has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Healios. Dr. Hansen has received personal compensation for serving as an employee of Novo Nordisk A/S. Dr. Hansen has stock in Novo Nordisk A/S. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ACADIA. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alkahest. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Green Valley. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Grifols. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Otsuaka. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for United Neuroscience. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Cummings has received research support from NIH. Dr. Cummings has received intellectual property interests from a discovery or technology relating to health care.