As a potential disease-modifying treatment for AD, Alzhemed (tramiprosate) is a compound that binds to soluble amyloid-beta peptide (Aβ) and inhibits the formation of neurotoxic aggregates that lead to amyloid plaque deposition in the brain. The safety, tolerability, and pharmacodynamic effects of Alzhemed were assessed in a double-blind study in which 58 individuals with mild-to-moderate AD (MMSE 13-25) were randomized to receive placebo or Alzhemed 50, 100 or 150 mg BID for 3 months. At the end of the double-blind phase, 42 of these subjects entered a 36-month openlabel (OL) phase in which they received Alzhemed 150 mg BID. Assessments included plasma and cerebrospinal fluid (CSF) Alzhemed concentrations, CSF levels of Aβ, as well as cognitive (Alzheimers Disease Assessment Scale-cognitive subscale, Mini-Mental State Examination) and clinical performance (Clinical Dementia Rating scale, Sum-of-Boxes) measures. Alzhemed was safe and well tolerated, crossed the blood-brain barrier, and dose-dependently reduced CSF Aβ42 levels after 3 months of treatment. Mild AD subjects (MMSE 19-25 at entry) displayed greater reduction of CSF Aβ42 levels than moderate AD participants (MMSE 13-18 at entry). There was no effect of Alzhemed on the cognitive or clinical measures after 3 months of treatment. The OL follow-up suggested a stabilization of cognitive function especially in mild AD subjects over the 36-month study period. Alzhemed thus appears to be well tolerated with long-term exposure and reduces CSF Aβ42 levels in mild-to-moderate AD subjects. These findings will be discussed in the context of two large-scale randomized, double-blind, placebo-controlled Phase III clinical trials that are currently being conducted to test the long-term safety and efficacy of Alzhemed.