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Masupirdine Improves Agitation and Aggression in Alzheimer Disease

A phase 3 trial has been initiated to further study masupirdine’s effect on agitation in patients with Alzheimer dementia.

Findings from the phase 2a multicenter, randomized, double-blind, proof-of-concept trial (NCT02580305) were presented at the 14th Clinical Trials on Alzheimer’s Disease Conference (CTAD), November 9-12, 2021. The study spanned a total of 26 weeks, with patients receiving a 50-mg dose of masupirdine, a 100-mg dose of masupirdine, or placebo. 

Investigators, led by Ramakrishna Nirogi, PhD, vice president, Suven Life Sciences, conducted subgroup analyses on the agitation/aggression domain of the 12-item neuropsychiatric inventory scale (NPI-A/A), based on independent patient subgroups and baseline symptoms. Patients who had a baseline NPI-A/A score of 1 point or greater were randomized to receive placebo (n = 57), masupirdine 50 mg (n = 54), or masupirdine 100 mg (n = 48). A significant mean change from baseline was identified in both the 50 mg (P <.001) and 100 mg (P = .007) groups when compared with placebo at week 26. 

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Similarly, in the group of patients with a baseline NPI-A/A score of 3 points or higher, investigators observed a significant mean change from baseline in the masupirdine 50-mg group (n = 30) at both week 13 (P = .012) and week 26 (P = .031) when compared with placebo. A significant change was also seen in the masupirdine 100-mg group (n = 21) at week 26, when compared with placebo (P = .024). Also noted were sustained effects of masupirdine for the entirety of the 26-week study, with no evidence of sedation in relation to treatment observed. 

A phase 3 study has been initiated to further study masupirdine’s effect on agitation with Alzheimer dementia, enrolling approximately 387 patients for a study period of 36 months. Topline results are anticipated to be presented by the end of 2024.2 

Masupirdine demonstrated a significant attenuation of psychosis in patients with dementia, representing a potential new treatment option for this patient population. In a separate presentation at CTAD, investigators presented additional findings the phase 2a study, which included 564 patients with moderate AD. While the study did not meet 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 AD duration.

Patients in each group were evaluated on domains of the NPI-12. Using a mixed-effects model for repeated measures, the effect size (Cohen 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.

The study authors concluded that the treatment "may have potential to address limitations of current pharmacological interventions." At baseline, those in the 50- and 100-mg groups had Alzheimer’s Disease Assessment Scale for Cognitive Behavior 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 0.48-0.57.3

For more coverage of CTAD 2021, click here.

REFERENCES
1. Nirogi R, Shinde A, Mohammed AR, et al. Beneficial effects of masupirdine on agitation in patients with Alzheimer disease: A novel non-sedating mechanism. Presented at CTAD 2021; November 9-12. Poster LRP10.
2. Suven Life Sciences announces phase 3 clinical trial of SUVN-502 (Masupirdine) a 5-HT6 antagonist for treatment of agitation and aggression in Alzheimer type dementias. News release. Suven Life Sciences. August 17, 2021. Accessed November 15, 2021. https://www.firstwordpharma.com/node/1855886
3. Nirogi R, Shinde A, Mohammed AR, et al. Beneficial effects of masupirdine on psychosis in patients with Alzheimer disease, addressing limitations of current pharmacological interventions. Presented at CTAD 2021; November 9-12. Poster LRP1.