Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the manifestation of neuropsychiatric symptoms throughout its course. Although not all neuropsychiatric symptoms are debilitating, agitation is among the most distressing for both the patient and the caregiver. It is also associated with rapid disease progression and early institutionalization. There remains a void in the available treatment options for managing agitation.

Masupirdine is a pure, potent, and orally active serotonin-6 (5-HT₆) receptor antagonist. Its effects on aggressive behaviors were evaluated using the rat models of resident intruder task and dominant-submissive assay. Additionally, Masupirdine’s impact on brain neurotransmitter modulation was assessed using the microdialysis technique in rats.

Subgroup analysis of a Phase-2 study targeting cognition in AD patients showed Masupirdine significantly decreases the agitation associated with AD, which warrants further evaluation. A Phase-3 pivotal global study (NCT05397639; EudraCT: 2021-003405-22) targeting Masupirdine for the treatment of agitation in patients with Alzheimer’s dementia is currently underway.

Findings from animal models suggest that Masupirdine reduces aggressive behaviors and modulates neurotransmitters involved in agitation. Analyses from the Neuropsychiatric Inventory 12-item (NPI-12) scale used in the Phase-2 clinical trial supports the beneficial effects of Masupirdine on agitation. Furthermore, Masupirdine was found to be safe and well tolerated in AD patients. A Phase-3 study is currently ongoing in the USA and Europe to substantiate Masupirdine’s effects on agitation. The demographic and baseline characteristics of the enrolled patients are consistent across regions and representative of the typical AD population experiencing agitation.

Approximately 45% of the total study population have been enrolled. Results from the Phase-3 study will inform the utility of Masupirdine in treating agitation in Alzheimer's dementia.