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The Cassava Sciences agent showed 6-month improvements in both ADAS-Cog and NPI scores, and a phase 3 trial is expected to begin in late 2021.
An original version of this article was published online by sister publication NeurologyLive.
A new investigational, oral small molecule treatment could aid in improving the cognitive behavior of patients with Alzheimer disease (AD).
Cassava Sciences, the manufacturer of simufilam, announced the findings from a recent open-label study and noted that in combination with prior clinical trial results, they support the advancement of simufilam into a phase 3 clinical program in AD. That trial is currently expected to begin in the second half of 2021.
Additionally, the US Food and Drug Administration (FDA) concluded a successful end-of-phase 2 meeting for the drug’s development program, the details of which Cassava anticipates announcing after official meeting minutes are finalized. The enrollment target for this current open-label study is planned to be increased by up to 50 additional patients, for a total target of approximately 150 patients, Cassava announced.
“We could not be more pleased with these interim results,” Remi Barbier, chief executive officer and president, Cassava, said in a statement. “We would have been satisfied to show simufilam stabilizes cognition in patients over 6 months. An improvement in cognition and behavior tells us this drug candidate has [the] potential to provide lasting treatment effects for people living with Alzheimer’s disease. It’s an exciting development.”
The study, funded by the National Institutes of Health (NIH), showed that after 6 months of treatment with the altered filamin A (FLNA) restoration agent that cognition scores measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) improved by 1/6 points from baseline scores of 15.5, equivalent to a 10% mean improvement.
Additionally, dementia-related behavior—including anxiety, delusions, and agitation—improved by 1.3 points from baseline scores of 4.5 on the Neuropsychiatric Inventory (NPI). This improvement equaled a 29% mean improvement at 6 months.
The 1-year, open-label, multi-center study is still ongoing, and seeks to evaluate the long-term safety and tolerability of 100-mg simufilam, administered twice daily to 100 patients with mild-to-moderate AD. It began in March 2020 and is now approximately 80% enrolled, according to Cassava Sciences.
“Today’s pre-planned interim analysis summarizes clinical data at the midway point of enrollment, i.e., the first 50 patients who have completed at least 6 months of drug treatment,” the company stated.
Cassava noted that by its nature, the open-label data are limited to an extent, a fact that must be taken into account by comparison to fully completed, large, randomized controlled trials.
The company noted that prior clinical research in AD can provide context as a reference for the rates of expected decline in placebo patients, citing Biogen/Eisai’s trial EMERGE (which notably was cut short due to futility, causing much debate about the agent being assessed), as well as Eisai’s phase 3 evaluation of donepezil (Aricept).
In EMERGE, those on placebo showed a mean decline in cognition of approximately 1.4 points on the ADAS-Cog13 (–6.3% from baseline to month 6), with a mean baseline ADAS-Cog13 score of 22.2 and a mean baseline Mini-Mental State Exam (MMSE) score of 26.4.
In the donepezil trial, patients on placebo showed a mean decline in cognition of approximately 1.9 points on ADAS-Cog, a 7.3% decline, from baseline to week 24. The mean baseline ADAS-Cog score was 26 and the MMSE score range was 10-26.