Simufilam 100 mg for Mild-to-Moderate Alzheimer's Disease

Summary

A 52-week safety and efficacy study of simufilam (PTI-125) given twice daily to participants with mild-to-moderate Alzheimer's disease (AD) for 52 weeks. Approximately 750 participants will be randomized (1:1) to receive either placebo or 100 mg tablets of simufilam, twice daily, for 52 weeks. Clinic visits will occur 4 weeks after the baseline visit, and then every 12 weeks until the end of the study. The safety of simufilam, and its efficacy in enhancing cognition and slowing cognitive and functional decline will be evaluated.

Timeline

Start

2021-11-03

Primary completion

2024-10-02

Completion

2024-10-02

Outcome

Missed primary endpoint

registry analysis (superiority test); Simufilam 100 mg vs Placebo; p = 0.4308; Mean Difference (Final Values) -0.39 (95% CI -1.37 to 0.59); Mixed Models Analysis NCT04994483 ↗

registry analysis (superiority test); Simufilam 100 mg vs Placebo; p = 0.4034; Mean Difference (Final Values) 0.51 (95% CI -0.68 to 1.70); Mixed Models Analysis NCT04994483 ↗

paper Both trials failed to meet co-primary, secondary or exploratory biomarker endpoints. PMID 41500915 ↗

release “following the report that a prior 52-week Phase 3 study, RETHINK-ALZ, did not meet its co-primary endpoints.” filanatx.com ↗

Publications

• Kupiec JW, Porsteinsson AP, Turner RS, Hendrix S, Mallinckrodt C, Khan A, Cohen I, Liss J, Clarnette R, Park KH, Hernandez AM, Burns LH. Phase 3 randomized clinical trials of simufilam in mild-to-moderate Alzheimer's disease. J Prev Alzheimers Dis. 2026 Mar;13(3):100469. doi: 10.1016/j.tjpad.2025.100469. Epub 2026 Jan 6.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Simufilam	Small molecule	100 mg	Oral

Indications