This decision was made due to observations of mild cognitive decline and brain atrophy in participants.446,447 Elenbecestat (15, E2609), a fourth-generation BACE1 inhibitors, was among the last BACE1 inhibitors to reach phase III clinical trials.448 A phase III trial (NCT02956486) assessing effectiveness and safety in early-stage AD patients was terminated due to an unfavorable risk-benefit ratio. This evidence concerns the gene BACE1 and Alzheimer disease.