Therapeutic Potential of Oral ALZ-801 in Patients with Alzheimer's Disease.

Alzheimer's disease (AD), the most common cause of dementia, is characterized by amyloid-β (Aβ) plaques in the brain. ALZ-801, a prodrug of tramiprosate, was developed as an oral disease-modifying therapy for patients with AD. Tramiprosate and ALZ-801 inhibit Aβ aggregation and reduce Aβ-induced cytotoxicity. Although the prespecified endpoints were not met in two Phase 3 trials involving tramiprosate, post hoc analyses indicated benefits in apolipoprotein E ε4 homozygotes. Furthermore, no cases of amyloid-related imaging abnormalities-edema/effusion were detected. In the APOLLOE4 Phase 3 study of ALZ-801 in apolipoprotein E ε4 homozygous patients with early AD, the primary endpoint was not achieved; however, the mild cognitive impairment subgroup demonstrated nominal efficacy. ALZ-801 has not been associated with amyloid-related imaging abnormalities, a major safety concern of anti-Aβ antibodies, and may represent a safe oral alternative to anti-Aβ antibody therapies.