In a phase 2b study (NCT04079803) of sumifilam (PTI-125; Cassava Sciences, Austin, TX) for potential treatment of Alzheimer disease (AD), there was directional improvement in episodic and spatial memory. In addition, treatment with sumifilam resulted in significant changes to levels of validated disease biomarkers.
Participants treated with sumifilam 100 (n=21) or 200 mg/day (n=21) in 2 divided doses had improvement on episodic and spatial memory tests of 17% to 46% after 28 days of treatment compared with those treated with placebo (n=22). In those taking 100 or 200 mg/day of sumifilam, episodic memory improved by 5.7 points and 4.3 points, respectively, compared with a decline of 1.5 points in individuals treated with placebo. Spatial memory improved by 1.6 and 3.3 points, respectively, for those treated with 100 or 200 mg/day of sumifilam vs a decline of 0.4 points for those treated with placebo.
Participants treated with 100 or 200 mg/day sumifilam had a 15% and 18% decrease in T-tau brain levels, respectively, and an 8% and 11% reduction in P-tau brain levels, respectively (P<0.01 for all measures) compared with those treated with placebo. Cognitive improvements correlated most strongly (R2=.5) with decreases in P-tau181. In those who had biomarker improvements, there was a 98% response rate on cognitive measures.
The study was a phase 2b randomized placebo-controlled double-blind multicenter clinical study that enrolled 64 participants with mild-to-moderate AD, age 50 to 85, who were randomly assigned to be treated with 100 mg/day or 200 mg/day in 2 divided doses daily for 28 days.
Chen Zhao, MD; Jonathan G. Hakun, PhD; Krishnankutty Sathian, MBBS, PhD; and Nikolaos Scarmeas, MD, MS, PhD
Magdalena Szaflarski, PhD