Sumifilam (formerly PTI-125) is an experimental therapy being developed by Cassava Sciences to treat Alzheimer’s disease, a progressive and neurodegenerative condition.

How does sumifilam work?

Proper folding of a protein is vital for it to work as intended. Alzheimer’s disease is a complex brain disorder thought to be caused by the incorrect folding of several proteins. These misfolded proteins clump together in the brain, creating plaques that impede brain function and lead to inflammation, degeneration, and atrophy in nerve cells.

Filamin A is one of the misfolded proteins found in Alzheimer’s disease. Filamin A is a scaffolding protein, a type of protein that helps the proper folding of other proteins. Correctly functioning filamin A is essential for the proper folding and working of amyloid-beta and tau, two proteins that play a crucial role in the development of Alzheimer’s. In its altered form, filamin A prevents the proper folding of the amyloid-beta and tau proteins, causing them to aggregate and form plaques and tangles in the brain. Misfolded filamin A also disrupts how nerve cells work, leading to the neurodegeneration observed in people with Alzheimer’s disease.

Sumifilam is an investigational small molecule that targets the misfolded filamin A protein. It binds to this filamin A and aims to restore its function, potentially alleviating the symptoms of Alzheimer’s disease.

Sumifilam in clinical trials

Sumifilam was also shown to be safe and well-tolerated in a Phase 1 clinical trial (NCT03784300) that evaluated its safety and pharmacokinetics (movement in the body) in healthy volunteers.

A Phase 2a open-label clinical trial (NCT03748706) investigated the safety and pharmacokinetics of sumifilam in a group of mild-to-moderate Alzheimer’s patients. Study results showed that treatment, 28 days of sumifilam at 100 mg twice daily, was well-tolerated, and these 13 patients had markedly lower disease-specific biomarkers of neuroinflammation and neurodegeneration.

A randomized, placebo-controlled, multiple-dose Phase 2b clinical trial (NCT04079803) evaluated the safety, tolerability, and effectiveness of two doses of sumifilam in people with mild-to-moderate Alzheimer’s disease. The study enrolled 64 patients, ages 50 to 85, at eight U.S. sites. Participants were randomized to receive either 50 mg or 100 mg oral tablets of sumifilam, or a placebo, twice a day. After 28 days of treatment or placebo, a cerebrospinal fluid (the fluid surrounding the brain and spinal cord) sample was assessed for biomarkers of Alzheimer’s disease. Researchers also evaluated markers of neurodegeneration and neuroinflammation in all patient groups. Secondary study goals were blood levels of disease biomarkers, and evidence of changes in learning skills and memory.

Results of the trial were not able to show a statistically significant change in biomarkers for the disease between the treatment groups and placebo. Further analysis of the data suggested that there was a large amount of variability in the biomarkers even just in the placebo group with some patients increasing biomarker levels while others decreased in those same biomarkers. The large variability in biomarker levels potentially concealed any improvements from the treatment. The treatment was found to be safe and well-tolerated, however.

An open-label Phase 2 trial (NCT04388254) is recruiting new patients or those who participated in either of the previous two Phase 2 trials. The study aims to recruit 100 patients with mild-to-moderate Alzheimer’s disease at multiple locations in the U.S. All patients will receive 100 mg of sumifilam twice a day for 12 months in order to establish the long-term safety and tolerability of treatment as well as changes in Alzheimer’s disease biomarkers, cognitive symptoms, and behavioral symptoms. The study is estimated to conclude in April 2022.

 

Last updated: Nov. 22, 2020

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Alzheimer’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Vijaya Iyer is a freelance science writer for BioNews Services. She has contributed content to their several disease-specific websites, including cystic fibrosis, multiple sclerosis, muscular dystrophy, among others. She holds a PhD in Microbiology from Kansas State University, where her research focused on molecular biology, bacterial interactions, metabolism, and animal models to study bacterial infections. Following the completion of her PhD, Dr. Iyer went on to complete three postdoctoral fellowships at Kansas State University, University of Miami and Temple University. She joined BioNews Services to utilize her scientific background and writing skills to help patients and caregivers remain abreast with important scientific breakthroughs.
Total Posts: 3
Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.
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Vijaya Iyer is a freelance science writer for BioNews Services. She has contributed content to their several disease-specific websites, including cystic fibrosis, multiple sclerosis, muscular dystrophy, among others. She holds a PhD in Microbiology from Kansas State University, where her research focused on molecular biology, bacterial interactions, metabolism, and animal models to study bacterial infections. Following the completion of her PhD, Dr. Iyer went on to complete three postdoctoral fellowships at Kansas State University, University of Miami and Temple University. She joined BioNews Services to utilize her scientific background and writing skills to help patients and caregivers remain abreast with important scientific breakthroughs.
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