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Sumifilam (PTI-125)

Sumifilam (formerly PTI-125) is an experimental therapy that Cassava Sciences is developing for Alzheimer’s disease. The investigational small molecule is designed to ease patients’ cognitive symptoms.

How does sumifilam work?

The proper folding of proteins is vital for them to work correctly. Alzheimer’s disease is a complex brain disorder. Researchers think that the incorrect folding of several proteins plays a role in the development of the disease. These misfolded proteins clump together in the brain, forming plaques. These plaques may impede brain function and lead to inflammation, degeneration, and atrophy in nerve cells.

Filamin A is one of the misfolded proteins in Alzheimer’s. It 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 role in the development of Alzheimer’s. In its altered form, filamin A prevents the proper folding of the amyloid-beta and tau proteins. This causes them to aggregate, or clump, and form plaques and tangles in the brain. Misfolded filamin A also disrupts how nerve cells work, leading to neurodegeneration in people with the disease.

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

Sumifilam in clinical trials

A Phase 1 clinical trial (NCT03784300) involving healthy volunteers, completed in 2018, evaluated sumifilam’s safety and pharmacokinetics, or its movement in the body. The results showed it was safe and well-tolerated.

An open-label Phase 2a clinical trial (NCT03748706), which wrapped up in 2019, investigated the safety and pharmacokinetics of sumifilam in 12 patients with mild to moderate Alzheimer’s. Study results showed that 28 days of sumifilam treatment, at 100 mg twice daily, was well-tolerated and that 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. The study enrolled 64 patients, ages 50 to 85, at eight U.S. sites. Researchers randomly assigned participants to receive either 50 mg or 100 mg oral tablets of sumifilam, or a placebo, twice a day.

After 28 days of treatment, samples of the participants’ cerebrospinal fluid (CSF), the liquid surrounding the brain and spinal cord, were assessed for biomarkers of Alzheimer’s disease. The team 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.

The results of the trial, completed in 2020, did not show a statistically significant change in disease biomarkers between the treatment and placebo groups. However, further analysis of the data suggested that there was a large amount of variability in the biomarkers even in just the placebo group. Notably, some patients were found to have high levels of biomarkers while others had low levels. That large variability in biomarker levels potentially concealed any improvements from the treatment, the researchers said. The treatment was safe and well-tolerated, however.

Now, final data from the trial showed that, compared with a placebo, both the 50 and 100 mg dose of sumifilam were actually able to significantly lower the levels of all biomarkers in the CSF within 28 days.

In general, the reductions were stronger in patients receiving the higher dose of the treatment. Researchers recorded these responses in 98% of the participants who received sumifilam. The treatment also improved the cognitive abilities of the patients compared with a placebo. These improvements correlated with reductions in the CSF levels of the biomarkers.

Ongoing clinical trials

An open-label Phase 2 trial (NCT04388254) is currently recruiting both new patients and those who participated in either of the previous two Phase 2 trials.

It seeks to enroll 100 people 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. The aim is to establish the long-term safety and tolerability of the treatment. Researchers also will assess any changes in Alzheimer’s disease biomarkers, cognitive symptoms, and behavioral symptoms.

The study is estimated to be completed in April 2022.

Sites are now open in Arizona, Florida, Nebraska, New Jersey, and Texas. More information on contacts and locations is available here.


Last updated: Feb. 11, 2020


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.

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