Over 26 weeks of treatment, masupirdine demonstrated a sustained and durable effect on outcomes such as cognition and dementia-related psychosis.
A sub-analysis of treatment with masupirdine (SUNV-502; Suven Life Sciences), a pure 5-HT6 receptor antagonist, demonstrated a significant attenuation of psychosis in patients with dementia and may represent a new treatment option currently unavailable to this patient population.1
Although the phase 2a clinical trial (NCT02580305) missed its primary end point,2 potential beneficial effects on cognitive and behavioral outcomes were observed, providing motivation for additional sub-analyses considering combinations of patients’ age, memantine regimen, memantine plasma concentration, memantine treatment duration, and Alzheimer disease (AD) duration. Data from this latest analysis were presented at the 14th Clinical Trials on Alzheimer’s Disease Conference (CTAD), November 9-12, 2021, by Ramakrishna Nirogi, vice president, Suven Life Sciences.
Patients included in the subgroup analysis received either masupirdine 50 mg (n = 48), 100 mg (n = 50), or placebo (n = 57) and were evaluated on domains of the 12-item Neuropsychiatric Inventory Scale (NPI-12). Using a mixed-effects model for repeated measures, the effect size (Cohen’s d) on psychosis in the masupirdine treatment groups were 0.31-0.58 at the end of week 13 and between 0.24-0.35 at the conclusion of the 26-week treatment period.
At baseline, those in the 50- and 100-mg groups had Alzheimer’s Disease Assessment Scale for Cognitive Behavior (ADAS-Cog-11) scores of 29.62 (standard deviation [SD], 8.14) and 31.40 (SD, 9.17), respectively. At the end of the 26-week treatment period, the effect size on cognition with masupirdine treatment was between 0.48-0.57. The study authors concluded that the treatment "may have potential to address limitations of current pharmacological interventions."
The proof-of-concept trial began enrolling patients with probable Alzheimer disease (AD) in September 2015 and used change in ADAS-Cog-11 as the primary end point, with change on the Clinical Dementia Rating and various clinical and functional scales as secondary outcomes. The triple-therapy design included patients treated with stable doses of both donepezil 10 mg/day and memantine 10 mg twice/day or memantine hydrochloride extended release 28 mg/day or 28 mg memantine HCI extended-release with 10 mg donepezil HCI/day for at least 3 months.2
In August, the company announced the initiation of a global phase 3 trial for the treatment of agitation and aggression in Alzheimer-type dementias. This multicenter trial comprising of approximately 387 patients is likely to be completed in about 36 months, with topline results expected by the end of 2024, according to Suven.3
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