More failure with solanezumab - this time in preclinical Alzheimer's disease

There is no cure for Alzheimer's disease, which is the sixth leading cause of death in the USA. Lecanemab is anti-Aβ monoclonal antibody approved for the treatment of early Alzheimer's disease but is only marginally effective. Other antibodies are being developed including solanezumab.

A phase 3 clinical trial of solanezumab in preclinical Alzheimer's disease. In the A4 study, solanezumab did not reduce the decline in cognition or function and had no effect on brain amyloid burden.

After the poor results in the EXPEDITION series of trials, the development of solanezumab should have been terminated. The rationale for undertaking the A4 trial was questionable, and the lack of benefit was probable. The controversial approval of two anti-Aβ monoclonal antibodies (aducanumab and lecanemab) for the treatment of Alzheimer's disease by the US Food and Drug Administration (FDA), despite a high incidence of amyloid-related imagining abnormalities (ARIA), may be fueling this continuation of clinical development of agents such as solanezumab. The lesson from the A4 trial is that more careful/realistic consideration needs to be given before embarking on further phase 3 trials with anti-Aβ monoclonal antibodies.