Masupirdine (SUVN‐502) for the Potential Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type: Preliminary Efficacy and Phase‐3 Study Design

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder with manifestations in cognitive, functional and neuropsychiatric symptoms (NPS). Agitation is one of the most prevalent and challenging NPS to manage. Antipsychotics are widely used for the pharmacological management of agitation. However, they offer modest efficacy, and the side effects are substantial.Serotonin‐6 receptor (5‐HT6) blockade may have therapeutic utility in the management of disorders associated with mood and behavior. Masupirdine is a potent and selective 5‐HT6 receptor antagonist.MethodMasupirdine has been evaluated in a phase‐2, 26‐week proof‐of‐concept clinical study (NCT02580305). Subgroup analyses of study results based on the neuropsychiatric inventory scale was carried out. Masupirdine was also evaluated in animal models to assess its effect on behavior and brain neurotransmitters modulations.A double‐blind, randomized, placebo‐controlled, parallel group, adequately powered global phase‐3 study is in progress to evaluate the efficacy, safety, tolerability, and pharmacokinetics of masupirdine for the treatment of agitation in participants with dementia of the Alzheimer’s type (NCT05397639). A total of 375 patients are planned to be enrolled in the study who will be randomly assigned to receive either 50 mg masupirdine or 100 mg masupirdine or placebo. Patients will be treated for 12 weeks. The primary efficacy endpoint of this study is the Cohen‐Mansfield Agitation Inventory items score aligning to the international psychogeriatric association agitation criteria domains (physical aggression, excessive motor activity, and verbal aggression) and the key secondary endpoint is improvement in modified Alzheimer’s Disease Cooperative Study‐Clinical Global Impression of Change score as related to agitation.ResultThe observations from the post hoc analysis of phase‐2 clinical study in AD patients and animal models support the potential beneficial effects of masupirdine on agitation.The phase‐3 study has been initiated in USA and Europe, and the subject enrolment is expected to be completed by Q3 2024.ConclusionThe need for new treatments for the management of agitation is significant and unmet. The Phase‐3 study results will inform the utility of masupirdine for the potential treatment of agitation in patients with dementia of Alzheimer’s type. Phase‐3 study data readout is anticipated in Q1/Q2 2025.