ALZ-801, oral pro-drug of tramiprosate, is in development as an Alzheimer’s disease (AD) treatment. Tramiprosate, the active molecule, is an amyloid anti-aggregation agent that inhibits formation of Aβ oligomers and neurotoxicity. In a Phase 3 study with tramiprosate, patients homozygous for the e4 allele of apolipoprotein E (APOE4/4 subgroup) showed significant efficacy over 78 weeks. Efficacy results for APOE4/4 patients who enrolled in extension study for an additional 52 weeks are presented.Method
78-week Phase 3 North American study enrolled 1,053 AD patients (MMSE range 16-26) including 148 APOE4/4 homozygotes in 3 arms: placebo, 100mg BID, 150mg BID. Patients completing 78 weeks were offered extension study at the high dose. Drug assignment during the placebo-controlled phase remained blinded. Change from original baseline in ADAS-cog and CDR-SB were analyzed using MMRM at all visits up to 130 weeks.Results
Total of 104 APOE4/4 homozygous patients enrolled in the extension study: 43, 33 and 28 from placebo, low and high-dose groups respectively; and 27, 25, 18 completed 130 weeks. The 150mg to 150mg group showed larger ADAS-cog benefits at both 104 and 130 weeks than the placebo to 150mg group (D = 3.9, p-value < 0.05), and a positive trend on CDR-SB (D = 1.0, p-value < 0.1). Adverse event profile was favorable, similar to blinded phase.Conclusion
APOE4/4 AD patients tramiprosate exhibited sustained cognitive and functional benefits over 2.5 years, compared to patients whose treatment was delayed by 78 weeks (delayed start group). Efficacy profile supports a disease-modifying benefit, consistent with amyloid anti-aggregation action.