Simufilam 50 mg or 100 mg for Mild-to-Moderate Alzheimer's Disease

Summary

A 76-week safety and efficacy study of simufilam (PTI-125) given twice daily to participants with mild-to-moderate Alzheimer's disease (AD) for 76 weeks. Approximately 1083 participants will be randomized (1:1:1) to receive either placebo, 50 mg tablets of simufilam, or 100 mg tablets of simufilam, twice daily, for 76 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

2021-11-18

Primary completion

2024-12-30

Completion

2024-12-30

Outcome

Missed primary endpoint

Stopped (Business): “Sponsor decision”

registry analysis (superiority test); Simufilam 50 mg vs Placebo; p = 0.5335; Mean Difference (Final Values) 0.45 (95% CI -0.96 to 1.86); Mixed Models Analysis NCT05026177 ↗

registry analysis (superiority test); Simufilam 100 mg vs Placebo; p = 0.5836; Mean Difference (Final Values) 0.38 (95% CI -0.99 to 1.76); Mixed Models Analysis NCT05026177 ↗

paper CONCLUSIONS: Simufilam did not meet co-primary or secondary endpoints in these Phase 3 trials. PMID 41500915 ↗

release “Topline data indicate that REFOCUS-ALZ did not meet each of the prespecified co-primary, secondary and exploratory biomarker 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	50 mg	Oral
Subject	Simufilam	Small molecule	100 mg	Oral

Indications