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Abstract Details

Positive Disease Modifying Effects of Oral ALZ-801 on Plasma Biomarkers, Volumetric MRI and Cognition at 104 Weeks: Results of a Phase 2 Study in APOE4 Carriers with Early Alzheimer’s Disease
Aging, Dementia, Cognitive, and Behavioral Neurology
ES1 - Emerging Science 1 (11:15 AM-11:21 AM)
001

ALZ-801 (valiltramiprosate), an oral brain-penetrant amyloid-oligomer inhibitor is completing a Phase 3 78-week trial in APOE4/4 homozygotes Early AD (EAD) subjects. The Phase 2 study evaluated its effects (265mg BID) on plasma biomarkers, MRI and cognition in EAD APOE4 carriers over 2 years. Plasma p-tau181 is elevated in AD and reduced by efficacious doses of lecanemab and aducanumab.

To evaluate ALZ-801’s effects on plasma and imaging biomarkers of Alzheimer’s disease (AD).

This 104-week, open-label study enrolled 84 subjects (MMSE 22-30, CDR-G 0.5-1, positive amyloid-PET or CSF biomarkers). Plasma and clinical testing were every 13 weeks, MRI every 52 weeks. Primary outcome was plasma p-tau181, cognitive tests were Rey Auditory-Verbal-Learning-Test (RAVLT) and Digit-Symbol-Substitution-Test (DSST). Dr. Blennow’s Laboratory (Sweden) conducted plasma biomarker analyses (Simoa, EuroImmun assays). Observed data changes-from-baseline were analyzed with 2-sided simple t-tests.

84 subjects were enrolled (51% female, age 69 years, MMSE 26.0, 70%/30% had MCI/Mild AD;70 completed 104-weeks. Plasma p-tau181 showed significant reductions at all timepoints reaching 31%-43% over 52-104 weeks (p=0.045), Aβ42 decreased ~4% over 104 weeks(p=0.042). Hippocampus atrophy (3.6%) was ~28% less than matched external control (ADNI-1 study). RAVLT-total memory and DSST improved at 26 weeks, remaining above/at baseline at 104 weeks; 50% and 33% of MCI and Mild AD subjects maintained their CDR-G stage. Cognitive stabilization correlated with decreased hippocampal atrophy (Spearman’s r=0.38-0.43, p≤ 0.002); and cortical thinning (r=0.35-0.58, p≤ 0.004). COVID-19 infection, nausea, decreased appetite were the main AEs, with no ARIA-E.

Over 2 years, oral ALZ-801 reduced plasma p-tau181 and Aβ42 significantly suggesting improved amyloid clearance. Cognitive stabilization correlated strongly with reduced brain atrophy, both showing treatment benefit compared to external control. No ARIA-E/vasogenic edema was detected. These biomarker results support the disease-modifying effects of ALZ-801 in Early ADwith promising clinical efficacy and favorable safety in APOE4 carriers.

Authors/Disclosures
James Kesslak (Alzheon)
PRESENTER
Dr. Kesslak has received personal compensation for serving as an employee of Alzheon. Dr. Kesslak has stock in Prime First Lending.
John Hey (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.
Sawsan (Susan) Abushakra 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 NIA. Dr. Abushakra has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file
Jakub Hort Dr. Hort has received personal compensation in the range of $0-$499 for serving as a Consultant for Alzheimerchain. Dr. Hort 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. Hort has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Schwabe. Dr. Hort has stock in Alzheon.
Niels Prins (Brain Research Center) Dr. Prins has stock in Brain Research Center. Dr. Prins has received personal compensation in the range of $100,000-$499,999 for serving as a CEO with Brain Research Center.
No disclosure on file
Adem Albayrak (Alzheon) Mr. ALBAYRAK has received personal compensation for serving as an employee of Alzheon.
Winnie Pak (Alzheon) Dr. Pak has received personal compensation for serving as an employee of Alzheon.
Aidan Power (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.
Martin Tolar (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.