Is Valiltramiprosate a Magic Pill for APOE4 carriers?

In this video, I analyze groundbreaking data from the Valiltramiprosate session that happened during the AAIC July 2025 showing unprecedented results for APOE4 carriers:

• 52% benefit on ADAS-cog, maintaining above baseline for 52 weeks (p=0.04)
• 102% benefit on CDR-SB, remaining at baseline for 78 weeks
• Zero ARIA-E or ARIA-H across all patients
• Hippocampal volume protection (p=0.04) correlating with clinical benefit (r=0.89)
• 16 million APOE4 homozygotes worldwide could benefit

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Timestamps
0:00 Introduction
1:40 10x toxicity comes from oligomers, not plaques
05:42 Prevention of oligomers sets valiltramiprosate apart in alzheimer's therapy
09:28 52% cognitive improvement in ApoE4 homozygotes
11:33 Preserved brain volume means better outcomes
16:26 Zero ARIA = Safe for ApoE4
18:05 ApoE4 carriers respond best with early treatment
21:28 The impact - 16M ApoE4 carriers
23:52 Conclusion

Source and credits to:
Alzheimer's Association International Conference July 2025

Session detail:
Pathogenic Role of Beta Amyloid Oligomers in Alzheimer’s Disease (AD)» Overview of amyloid cascade in AD» Differentiating beta amyloid species by neurotoxic profile» Measuring and detecting oligomers in AD patients

Insights into Mechanism of Action of Valiltramiprosate
Impact of valiltramiprosate on beta amyloid aggregation and oligomer formation
Anti-aggregation stoichiometry of beta amyloid monomer to valiltramiprosate
Implications for therapeutic utility of valiltramiprosate in ADQSP Analysis of Inhibition of Amyloid Oligomer Formation by Valiltramiprosate
Influence of APOE4 genotype on disease trajectory as measured by quantitative systems pharmacology (QSP)
QSP analysis linking amyloid-ß aggregation dynamics and neurodegeneration by hippocampal atrophy
Valiltramiprosate effects on Aβ aggregation dynamics, hippocampal atrophy & AD trajectory
Disease Modifying Effects of Valiltramiprosate in Early Symptomatic AD» Development of valiltramiprosate: an optimized prodrug
Disease modifying effects of valiltramiprosate in early symptomatic AD
Stage-dependent effects of valiltramiprosate linked to MOA

Presenters:
Sharon Cohen, M.D.
Sam Gandy, M.D., Ph.D.
Kenjiro Ono, M.D., Ph.D.
Hugo Geerts, Ph.D.
John Hey, Ph.D.