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Abstract Details

Correlations between Clinical and Brain Volume Effects of Oral Valiltramiprosate in APOE4/4 Homozygotes with MCI: Pre-specified Analyses of the Phase-3 APOLLOE4 78-Week Trial in APOE4/4 Homozygotes with Early Alzheimer’s Disease (AD)
Aging, Dementia, and Behavioral Neurology
P6 - Poster Session 6 (5:00 PM-6:00 PM)
12-010
To evaluate valiltramiprosate/ALZ-801 effects on clinical and brain volume outcomes and their correlations over 78 weeks.
Valiltramiprosate/ALZ-801, an oral small molecule inhibitor of amyloid-beta (Aβ) oligomer formation, was evaluated in APOE4/4 homozygotes with Early AD (NCT04770220). Hippocampal atrophy, an early neuropathological change in AD, is prominent in APOE4/4 homozygotes and is associated with clinical decline.
A total of 325 homozygotes (placebo, 265mg BID, randomized 1:1) stratified by MCI (MMSE 27-30) or Mild AD (MMSE 22-26),were enrolled. Primary and key secondary outcomes were ADAS-Cog13 and CDR-SB respectively, DAD was a secondary outcome. Volumetric MRI, collected every 26 weeks, was centrally analyzed for quantitative brain volumes. HV was the main imaging outcome, with secondary measures of cortical thickness (CT) and whole brain volume (WBV). MMRM was main analysis model, analyses by disease stage were prespecified; Spearman’s correlations of drug effects are presented.
In overall population, primary and secondary clinical outcomes were not significant but all vMRI outcomes showed significant atrophy slowing versus placebo (HV, 18% less atrophy, p=0.017). Prespecified, MCI (N=125), showed positive effects/trends on ADAS-Cog13 (52%, p=0.041), DAD (96%, p=0.016) and CDR-SB (102%, p=0.053); with significant atrophy slowing in HV (26%), CT (35%), both p< 0.01, and in WBV (22%, p=0.027). In MCI group, subject-level correlations between HV-ADAS (r=-0.45), HV-CDR (r=-0.46) were both significant (p<0.0001); clinical correalations for CT, WBV were also significant (correlation coefficients 0.39-0.51).
In the Phase 3 pre-specified MCI group, valiltramiprosate showed nominally significant cognitive and functional benefits with statistically significant atrophy slowing in all brain compartments (HV 26%, WBV 22%). Hippocampal and whole-brain volume effects showed significant subject-level correlations with cognitive and functional benefits over 78 weeks (correlations 0.45-0.49). These strong subject-level imaging-clinical correlations support the efficacy of valiltramiprosate in APOE4/4 MCI subjects.
Authors/Disclosures
Marwan N. Sabbagh, MD, FAAN (Barrow Neurological Institute)
PRESENTER 		Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genetech=Roche. Dr. Sabbagh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novo Nordisk. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Synaptogenix. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant Health. Dr. Sabbagh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Anavex. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cognito Therapeutics. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Sabbagh has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for CervoMed. Dr. Sabbagh has stock in Neurotau. Dr. Sabbagh has stock in Seq Biomarque. Dr. Sabbagh has stock in uMethod Health. Dr. Sabbagh has stock in Athira. Dr. Sabbagh has stock in Lighthouse Pharmaceuticals. Dr. Sabbagh has stock in Alzheon. The institution of Dr. Sabbagh has received research support from NIH. The institution of Dr. Sabbagh has received research support from ADDF.
Susan Abushakra, MD Dr. Abushakra has received personal compensation for serving as an employee of Alzheon Inc.. Dr. Abushakra has stock in Alzheon Inc.. The institution of Dr. Abushakra has received research support from NIH. Dr. Abushakra has received intellectual property interests from a discovery or technology relating to health care.
Duygu Tosun, PhD Prof. Tosun has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alzheon. The institution of Prof. Tosun has received research support from NIH.
David A. Watson, PsyD Dr. Watson has nothing to disclose.
Aidan Power, PhD (Alzheon) Dr. Power has received personal compensation for serving as an employee of Alzheon. Dr. Power has stock in Pfizer. Dr. Power has stock in Alzheon.
Earvin Liang, PhD (Alzheon) Dr. Liang has nothing to disclose.
Emer MacSweeney (Re:Cognition Health) No disclosure on file
Mercè Boada Rovira, MD, PhD (Fundació ACE. Institut Català de Neurociènces Aplicades) Dr. Boada Rovira has received personal compensation for serving as an employee of FUNDACIO ACE. ICNA. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GRIFOLS. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ARACLON BIOTECH. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIOGEN. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MERCK. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ZAMBON. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GRIFOLS. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ARACLON BIOTECH. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ROCHE. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIOGEN. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for LILLY. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MERCK. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ZAMBON. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NOVO NORDISK. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIOIBERICA. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SERVIER. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SCHWABE PHARMA. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ROCHE. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOGEN. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GRIFOLS. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for NUTRICIA. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ARACLON BIOTECH. The institution of Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for SERVIER. Dr. Boada Rovira has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for ZAMBON.
karim bennys, MD Dr. bennys has nothing to disclose.
Jorge Matias Guiu Guia, MD (Hospital Clinico San Carlos) No disclosure on file
John A. Hey, PhD (Alzheon) Dr. Hey has received personal compensation for serving as an employee of Alzheon. Dr. Hey has stock in Alzheon. Dr. Hey has stock in Alzheon. Dr. Hey has received intellectual property interests from a discovery or technology relating to health care.
Susan M. Flint, MS (Alzheon) Ms. Flint has received personal compensation for serving as an employee of Alzheon. Ms. Flint has stock in Alzheon.
James P. Kesslak, PhD (Alzheon) Dr. Kesslak has received personal compensation for serving as an employee of Alzheon.
Luc Bracoud, MSc Mr. Bracoud has nothing to disclose.
Sarah Bray, PhD Dr. Bray has received personal compensation for serving as an employee of Amgen Ltd. Dr. Bray has stock in Amgen Ltd.
Martin Tolar, MD, PhD (Alzheon) Dr. Tolar has received personal compensation for serving as an employee of Alzheon. Dr. Tolar has received intellectual property interests from a discovery or technology relating to health care.