Schneider LS, Thomas RG, Hendrix S, et al. - Researchers investigated the safety and efficacy of edonerpic maleate, an experimental drug that protects against neurotoxic effects, preserves synapses, and improves memory deficits in preclinical models related to Alzheimer disease, in patients with Alzheimer disease. Researchers conducted a randomized phase 2 clinical trial recruiting 484 patients with mild to moderate Alzheimer disease treated with cholinesterase inhibitors with or without memantine at 52 US clinical and academic centers. Participants were randomly assigned (1:1:1 allocation) to receive a placebo or 224 mg or 448 mg of edonerpic maleate, once per day. Outcomes revealed no achievement of improved cognition or function with either dose of edonerpic over 52 weeks compared with placebo. Further, they identified no clear effects of edonerpic on amyloid, tau, or brain magnetic resonance imaging biomarkers. In advancing from preclinical testing, they identified no clinical proof of concept for edonerpic maleate for patients with mild to moderate Alzheimer disease.