New data published in The Journal of the Prevention of Alzheimer’s Disease reports on analyses of Phase 3 data for tramiprosate in patients with mild to moderate Alzheimer’s disease. This marks the first data from a large clinical study to correlate efficacy of an amyloid-targeted drug with APOE4 status in patients with Alzheimer’s disease. 

The efficacy analyses looked at patient subgroups based on the number of ε4 alleles of apolipoprotein E (APOE4). The data showed a gene-dose effect with high-dose tramiprosate 150mg twice daily in patients with two APOE4 alleles (APOE4/4 homozygotes) associated with the greatest clinical benefit. Patients with one APOE4 allele (APOE4 heterozygotes) showed an intermediate benefit, and APOE4 non-carriers exhibited no benefit from tramiprosate. Patients who were APOE4/4 homozygous that received high-dose tramiprosate showed efficacy benefit vs. placebo on both cognitive and functional measures in the Phase 3 analyses.  

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The cognitive outcome effects were significant at Week 65 (P=0.007) and Week 78 (P=0.043), corresponding to a 66% and 40% benefit from tramiprosate vs. placebo. Functional benefits were also seen at Week 65 with a positive trend favoring tramiprosate at Week 65 (P=0.063) and Week 78 (P=0.21).

Alzheon Inc., is currently developing ALZ-801, an optimized oral prodrug of tramiprosate designed to improve the pharmacokinetic and gastrointestinal tolerability profile, while keeping tramiprosate as the active agent. It is being evaluated as a potential disease-modifying drug in symptomatic Alzheimer’s disease patients who are APOE4/4 homozygotes.

Martin Tolar, MD, PhD, Founder, President and CEO of Alzheon said, “To our knowledge, this is the first time that the clinical benefits of an amyloid-targeted agent have been associated with the number of APOE4 alleles in Alzheimer’s patients. This new insight shows how we can apply a precision medicine approach in AD and develop this drug for the right patients, namely patients with the APOE4 genotype, which carries the highest risk as well as the earliest onset and faster disease progression.”

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