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Encouraging interim results at 9 months from an open‐label study of simufilam in patients with Alzheimer’s disease
Author(s) -
Burns Lindsay H,
Doehner Tamara,
Puente John,
Beck Brian,
GonzalezRojas Yaneicy,
LopezBrigi Evelyn,
Nikolov Boris,
Wang HoauYan,
Pei Zhe,
Hernandez Antonio,
Crowley Carrie A,
Friedmann Nadav
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.054395
Subject(s) - tolerability , medicine , dementia , interim analysis , interim , adverse effect , disease , randomized controlled trial , archaeology , history
Abstract Background Simufilam is a novel drug candidate for Alzheimer’s disease (AD). This small molecule reverses an altered conformation of filamin A in the AD brain, reducing tau hyperphosphorylation and neuroinflammation initiated by Aβ 42 . In a prior randomized, controlled trial in 64 patients with mild‐to‐moderate AD, simufilam significantly improved eleven CSF biomarkers of AD pathology, neurodegeneration, neuroinflammation and blood‐brain barrier integrity over 28 days, with no safety issues. A one‐year, open‐label, multi‐center study is now evaluating simufilam’s long‐term safety and tolerability and following cognition and neuropsychiatric symptoms of dementia. The study has pre‐planned interim analyses at 6 and 9 months. Method Approximately 150 patients with mild‐to‐moderate AD, MMSE 16 to 26, will be enrolled across 16 sites in the US and Canada. Study participants receive 100 mg twice‐daily oral simufilam for one year. In addition to safety, patients are assessed on the 11‐item Alzheimer's Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog11) and the 10‐item Neuropsychiatric Inventory (NPI10). Result Interim results summarize data from the first 50 patients to complete at least 9 months of treatment. Simufilam was safe and well‐tolerated, consistent with prior safety results. Six months of treatment improved patients’ cognition scores by ‐1.6 points on ADAS‐Cog11, a 10% mean improvement from baseline (negative score indicates improvement). At 9 months, ADAS‐Cog11 scores improved by ‐3.0 points, a 19% mean improvement from baseline. At 9 months, 69% of patients showed improved or stable ADAS‐Cog11 scores from baseline. Mean baseline ADAS‐Cog11 score for these 50 patients was 16. Mean baseline MMSE was 22. Six months of treatment also improved NPI scores by ‐1.3 points, a 29% mean improvement from baseline (negative score indicates improvement). At 9 months, NPI scores improved by ‐0.7 points, a 16% mean improvement from baseline. At 9 months, 76% of patients showed improved or stable NPI scores from baseline. Mean baseline NPI10 score was 4.5. Conclusion Interim analyses at 6 and 9 months indicate open‐label treatment with simufilam 100 mg improved scores of cognition and neuropsychiatric symptoms in patients with Alzheimer’s disease, with no safety issues. This work was funded by NIA grant AG065152.