Effect of masupirdine (SUVN-502) on cognition in patients with moderate Alzheimer's disease: A randomized, double-blind, phase 2, proof-of-concept study

Ramakrishna Nirogi, John Ieni, Vinod Kumar Goyal, Jyothsna Ravula, Satish Jetta, Anil Shinde, Pradeep Jayarajan, Vijay Benade, Veera Raghava Chowdary Palacharla, Dhanunjay Kumar Dogiparti, Venkat Jasti, Alireza Atri, Jeffrey Cummings, Ramakrishna Nirogi, John Ieni, Vinod Kumar Goyal, Jyothsna Ravula, Satish Jetta, Anil Shinde, Pradeep Jayarajan, Vijay Benade, Veera Raghava Chowdary Palacharla, Dhanunjay Kumar Dogiparti, Venkat Jasti, Alireza Atri, Jeffrey Cummings

Abstract

Introduction: This study explored the efficacy and safety of a serotonin-6 receptor antagonist, masupirdine, as adjunct treatment in patients with moderate Alzheimer's disease (AD) concomitantly treated with donepezil and memantine.

Methods: The effects of masupirdine were evaluated in patients with moderate AD dementia on background treatment with donepezil and memantine. Five hundred thirty-seven patients were expected to be randomized in a 1:1:1 ratio, using permuted blocked randomization. After a 2- to 4-week screening period, the study consisted of a 26-week double-blind treatment period, and a 4-week washout period. The primary efficacy measure was the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog 11). Secondary efficacy measures were Clinical Dementia Rating Scale-Sum of Boxes, Mini-Mental State Examination, 23-item Alzheimer's Disease Co-operative Study Activities of Daily Living, and 12-item Neuropsychiatric Inventory. Changes from baseline were analyzed using a mixed effects model for repeated measures (MMRM). A total of 564 patients were randomized to receive either daily masupirdine 50 mg (190 patients), masupirdine 100 mg (185 patients), or placebo (189 patients). The study is registered at ClinicalTrials.gov (NCT02580305).

Results: The MMRM results showed statistically non-significant treatment differences in change from baseline in ADAS-Cog 11 scores at week 26, comparing each masupirdine dose arm to the placebo arm. No significant treatment effects were observed in the secondary evaluations.

Discussion: Masupirdine was generally safe and well tolerated. Possible reasons for the observed trial results are discussed.

Highlights: Masupirdine was evaluated in moderate Alzheimer's disease patients.First trial in class with background treatment of donepezil and memantine.Masupirdine was generally safe and well tolerated.Possible reasons for the observed trial results are discussed.

Keywords: 5‐HT6 receptor; Alzheimer's Disease Assessment Scale–Cognitive subscale; Alzheimer's disease; Clinical Dementia Rating–Sum of Boxes; SUVN‐502; clinical trials; masupirdine.

Conflict of interest statement

Dr. Cummings has provided consultation to AB Science, Acadia, Alkahest, AlphaCognition, ALZPathFinder, Annovis, AriBio, Artery, Avanir, Biogen, Biosplice, Cassava, Cerevel, Clinilabs, Cortexyme, Diadem, EIP Pharma, Eisai, GatehouseBio, GemVax, Genentech, Green Valley, Grifols, Janssen, Karuna, Lexeo, Lilly, Lundbeck, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Ono, Otsuka, PharmacotrophiX, PRODEO, Prothena, ReMYND, Renew, Resverlogix, Roche, Signant Health, Suven, Unlearn AI, Vaxxinity, VigilNeuro pharmaceutical, assessment, and investment companies. Dr. Alireza Atri has received honoraria for consulting; participated in independent data safety monitoring boards; provided educational lectures, programs, and materials; or served on advisory boards for AbbVie, Acadia, Allergan, the Alzheimer's Association, Axovant, AZ Therapies, Biogen, Eisai, Grifols, Harvard Medical School Graduate Continuing Education, JOMDD, Lundbeck, Merck, Roche/Genentech, Novo Nordisk, Qynapse, Sunovion, Suven, and Synexus. He receives royalties from Oxford University Press for a medical book on dementia. He receives institutional grant/contract funding from NIA/NIH 1P30AG072980, AZ DHS CTR040636, Washington University St. Louis, and Gates Ventures; and his institution receives funding for multiple clinical trial grants, contracts and projects from consortia, foundations, and companies for which he serves as site‐PI. Drs. Atri and Cummings did not receive compensation for developing this manuscript. John Ieni has provided consultation services for clinical development to Suven Life Sciences and Oligomerix, Inc. Ramakrishna Nirogi, Vinod Kumar Goyal, Jyothsna Ravula, Satish Jetta, Anil Shinde, Pradeep Jayarajan, Vijay Benade, Veera Raghava Chowdary Palacharla, Dhanunjay Kumar Dogiparti, Venkat Jasti are full‐time employees of Suven Life Sciences Ltd.

© 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.

Figures

FIGURE 1
FIGURE 1
Patient disposition. mITT, modified intent to treat population
FIGURE 2
FIGURE 2
Adjusted mean change in ADAS‐Cog 11 (mITT); error bars represent standard error of mean; ADAS‐Cog 11, 11‐item Alzheimer's Disease Assessment Scale, Cognitive Subscale; mITT, modified intent to treat population

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Source: PubMed

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