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Abstract Details

Effects of Oral Valiltramiprosate on Clinical Efficacy, Safety, and Brain Volume Outcomes in APOE4/4 Homozygotes with Early Alzheimer’s Disease (AD): Topline Results of the 78-week Phase 3 APOLLOE4 Trial
Aging, Dementia, and Behavioral Neurology
P1 - Poster Session 1 (8:00 AM-9:00 AM)
12-001
 To evaluate valiltramiprosate/ALZ-801 effects on clinical and brain volume outcomes in the prespecified MCI group.
Valiltramiprosate/ALZ-801, an oral small molecule inhibitor of amyloid-beta oligomer formation, was evaluated in a randomized, double-blind, placebo-controlled, 78-week trial in APOE4/4 homozygotes with Early AD (NCT04770220).
This trial randomized subjects 1:1 to placebo or valiltramiprosate 265 mg BID; stratified by MCI (MMSE 27-30) or Mild AD (MMSE 22-26). ADAS-Cog13 was the primary outcome, CDR-SB key secondary, functional DAD secondary outcomes, and hippocampal volume (HV) the main imaging outcome. MMRM was the main analysis model.
Safety population (N=325) was 51% females, mean age 69 years, MMSE 25.6, with 39% MCI and 61% Mild AD. In overall analysis population (N=320), ADAS-Cog13 placebo-adjusted effect favored drug non-significantly vs placebo (12%, p=0.61) and secondary outcomes were nonsignificant; however HV favored drug significantly (18% less atrophy, p=0.017). Prespecified Mild AD favored placebo nonsignificantly, but showed HV numerical benefit (12% less atrophy, p= 0.115). In prespecified MCI, all clinical outcomes favored drug (nominal p-values): ADAS-Cog13 (-2.14,p=0.042; 52%); CDR-SB (-0.65,p=0.053, 102%); DAD (+6.1, p=0.016, 96%). HV showed significant benefit versus placebo (108 mm3, 26% less atrophy, p= 0.004), with 35% and 22% less cortical and whole brain atrophy. Nausea (mostly mild) was the most common adverse event; ARIA-E incidence was same as placebo.

The overall population did not achieve significance on primary/secondary clinical outcomes, but showed significant slowing of hippocampal atrophy on valiltramiprosate (18% p=0.017). The pre-specified MCI group showed nominally significant positive effects on cognitive and functional outcomes, with 52% less cognitive decline, functional stabilization, significant slowing of hippocampal (26%) and whole brain atrophy (22%) over 78 weeks. Overall safety was favorable with no increased ARIA-E or ARIA-H. In the high-risk APOE4/4 population, this positive benefit-risk profile supports valiltramiprosate’s potential as an oral disease-modifying treatment for APOE4/4 homozygotes with MCI.
Authors/Disclosures
Susan Abushakra, MD
PRESENTER 		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.
Sharon Cohen, MD Dr. Cohen has nothing to disclose.
Marwan N. Sabbagh, MD, FAAN (Barrow Neurological Institute) 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.
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.
Anton P. Porsteinsson, MD (AD-CARE - University of Rochester School of Medicine) Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ONO Pharmaceuticals. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Porsteinsson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Porsteinsson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for WebMD. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Otsuka. Dr. Porsteinsson has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Porsteinsson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Xenon Pharmaceuticals. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Porsteinsson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cognitive Research Corporation. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Athira. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. The institution of Dr. Porsteinsson has received research support from Alector. The institution of Dr. Porsteinsson has received research support from Eisai. The institution of Dr. Porsteinsson has received research support from Eli Lilly. The institution of Dr. Porsteinsson has received research support from Athira. The institution of Dr. Porsteinsson has received research support from Genentech/Roche. The institution of Dr. Porsteinsson has received research support from Cassava. The institution of Dr. Porsteinsson has received research support from Vaccinex.
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.
Pierre J. Oussett No disclosure on file
Earvin Liang, PhD (Alzheon) Dr. Liang has nothing to disclose.
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.
Adem Albayrak (Alzheon) Mr. ALBAYRAK has received personal compensation for serving as an employee of Alzheon.
Sarah Bray, PhD Dr. Bray has received personal compensation for serving as an employee of Amgen Ltd. Dr. Bray has stock in Amgen Ltd.
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.
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.