Beyond lecanemab: Examining Phase III potential in Alzheimer's therapeutics

Abstract

This review focuses on the development of therapeutic interventions for Alzheimer's dementia. While established treatments targeted acetylcholine and NMDA receptors, there is a growing demand for innovative therapies as the aging population increases. The paper highlights the US Food and Drug Administration's approval of aducanumab (Aduhelm) and lecanemab (Leqembi), emphasizing the developmental status of new treatments. Specifically, it covers seven principal drugs in Phase III trials, detailing their mechanisms of action, clinical trial specifics in the United States and Japan, and the current status of regulatory applications. The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease-modifying small molecules (fosgonimeton, hydralazine, masitinib). However, Gantenerumab and Solanezumab, unsuccessful in Phase III, are not covered. While the future approval status remains uncertain, we hope these drugs will offer beneficial therapeutic effects for potential dementia patients.