1st Phase 3 Simufilam Trial Enrolling Patients; 2nd Expected by Year’s End

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by Patricia Inacio PhD |

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1st simufilam trial now enrolling patients/Alzheimer's News Today/enrollment image

MICHAIL PETROV/SHUTTERSTOCK

Cassava Sciences has launched the first of two Phase 3 clinical trials evaluating the safety and efficacy of simufilam, its investigational oral treatment for Alzheimer’s disease.

The second trial is expected to start by year’s end, the company said in a press release.

The first Phase 3 trial, called RETHINK–ALZ (NCT04994483), aims to enroll around 750 people, ages 50–87, with mild to moderate Alzheimer’s across 39 clinical sites in the U.S. and Canada. Additional overseas sites are expected to join the trial.

Currently, only one site is enrolling patients: the Rhode Island Mood & Memory Research Institute, in East Providence. More information on enrollment is available here.

Participants in this first study will be randomly assigned to receive either a placebo or 100 milligrams (mg) tablets of simufilam, twice daily, for 52 weeks, or one year.

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The trial’s main goals are to determine whether simufilam can improve cognition and participation in daily life activities compared with the placebo.

Changes in cognition will be assessed using the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS–Cog), while daily life activities will be evaluated using the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL). The ADCS–ADL assesses everyday tasks such as dressing oneself, preparing meals, watching TV, or engaging in conversations.

Additional goals include simufilam’s impact on disease biomarkers, neuropsychiatric symptoms, and caregiver burden.

The second Phase 3 trial, called REFOCUS–ALZ (NCT05026177) will evaluate the safety and effectiveness of two doses of simufilam — 50 and 100 mg — versus a placebo, delivered twice daily for 78 weeks (18 months).

The trial, to be conducted across 23 clinical sites in the U.S. and Canada, will enroll approximately 1,000 patients, also ages 50 to 87, with mild to moderate Alzheimer’s. Additional international sites are likely to be added. Enrollment is not yet open but more information can be found here.

Both trials are being conducted under a Special Protocol Assessment from the U.S. Food and Drug Administration. This formal procedure confirms whether certain important details of a trial’s protocol — such as the statistical analyses that will be used — meet the agency’s standards for an approval review.

“Alzheimer’s disease can have a devastating impact on patients, their families and caregivers,” said Remi Barbier, president and CEO of Cassava Sciences. “We believe existing drug solutions for Alzheimer’s have limitations, and new solutions are very much needed. Our Phase 3 studies are designed to evaluate the safety and efficacy of simufilam in people with Alzheimer’s disease.”

Simufilam is a small molecule designed to bind to an abnormal form of the protein Filamin A, called FLNA, which often is found with an abnormal shape — a 3D structure — in the brains of people with Alzheimer’s. FLNA is believed to participate in the processes driving the disease. By binding to FLNA, simufilam is designed to restore the protein’s normal structure and activity.

Previous results included in an interim analysis of an open-label Phase 2 clinical trial (NCT04388254) showed that six months of dosing with 100 mg tablets, taken twice daily, improved cognition and behavior in people with mild to moderate Alzheimer’s.