Simufilam found safe in review of ongoing Alzheimer’s clinical trials
Safety monitory board recommends 2 Phase 3 trials of oral therapy continue
After completing a third review of interim safety data, an independent safety monitoring board has recommended the continuation — without modifications — of two ongoing Phase 3 clinical trials testing the oral therapy simufilam in people with Alzheimer’s disease.
The board’s findings were announced by therapy developer Cassava Sciences, which said in a press release that the company expects to share data from one clinical trial later this year, and from the other by the middle of next year.
The two trials, dubbed RETHINK-ALZ (NCT04994483) and REFOCUS-ALZ (NCT05026177), have collectively enrolled 1,929 people with mild to moderate Alzheimer’s. The studies are testing simufilam’s safety and efficacy in improving the patients’ cognitive function.
“We are pleased to have satisfactorily completed this safety review, the last before the expected top-line read out for our first Phase 3 study,” said Jim Kupiec, MD, Cassava’s chief medical officer.
“We look forward to announcing top-line efficacy, safety, and biomarker data for our 12-month Phase 3 [RETHINK-ALZ] trial study before the end of 2024,” Kupiec said. Results from the REFOCUS-ALZ trial are expected by mid-2025.
Simufilam being tested in RETHINK-ALZ and REFOCUS-ALZ
Previous interim safety reviews of both trials indicated no relevant safety issues. Further, the treatment was not associated with brain swelling due to amyloid-related imaging abnormalities (ARIA), a risk seen with certain Alzheimer’s medications. Final clinical safety data for simufilam are expected when the Phase 3 program is completed.
Alzheimer’s disease is caused by the accumulation of toxic clumps of proteins in the brain, such as amyloid-beta and tau. Simufilam is an oral small molecule designed to target filamin A, a protein that forms abnormal clumps in Alzheimer’s and that’s also involved in amyloid-beta and tau clumping. By targeting filamin A, simufilam aims to reduce brain damage and slow disease progression. It’s also thought to have anti-inflammatory effects.
In a previous Phase 2 clinical trial (NCT04388254), which enrolled more than 200 people with mild to moderate Alzheimer’s disease, 47% of the patients treated with simufilam (100 mg twice daily) for a year saw improvements in their cognitive function.
In the RETHINK-ALZ trial, the 804 participants were randomly assigned to receive 100 mg of simufilam, or a placebo, twice daily for one year. The 1,125 patients in the REFOCUS-ALZ trial were given one of two doses of the treatment (50 or 100 mg), or a placebo, twice daily for about 1.5 years.
The main goal of both trials is to evaluate simufilam’s efficacy at improving patients’ cognitive function, assessed using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12), and their ability to perform activities of daily living independently using the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score.
RETHINK-ALZ is being conducted at 88 locations across the U.S., Australia, and Canada. REFOCUS-ALZ is testing simufilam at 89 locations in the U.S., Puerto Rico, the Republic of Korea, and Canada.
The company noted that the board only reviews patient safety and does not assess treatment efficacy.
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