Cassava Sciences, Inc. reported top-line results of a two-year clinical safety study of simufilam, an investigational oral drug for the proposed treatment of Alzheimer?s disease dementia. The study enrolled over 200 patients with mild to moderate Alzheimer?s and consisted of two open-label treatment phases and a randomized, placebo-controlled withdrawal phase. Average changes in ADAS-Cog scores, baseline to month 24, indicate the following: Patients with mild Alzheimer?s disease who received simufilam treatment continuously for two years (n=47) had no decline in ADAS-Cog scores (± 1.51 SE) as a group.

Patients with mild Alzheimer?s who received simufilam treatment non-continuously (n=40) declined 1 point on ADAS-Cog (± 1.65 SE) as a group. Non-continuous treatment consisted of one year on open-label drug, six months on placebo and six months back on open-label drug. In patients with mild Alzheimer's, the largest separation between the continuous and non-continuous treatment groups occurred at the end of the 6-month randomized, placebo-controlled withdrawal phase.

Patients with moderate Alzheimer?s who received simufilam treatment continuously for two years (n=32) declined 11.05 points on ADAS-Cog (± 1.91 SE) as a group. This was a 24-month safety study (NCT04388254). It included a pre-specified exploratory efficacy endpoint of mean change in ADAS-Cog11 scores.

The study enrolled over 200 patients with mild-to-moderate Alzheimer?s disease (MMSE 16-26) who were recruited from 16 U.S. clinical sites. The safety study was conducted in three continuous phases: a 12-month, open-label treatment phase, followed by a 6-month randomized, placebo-controlled withdrawal phase1, followed by 6 additional months of open-label treatment. Study participants received simufilam oral tablets 100 mg twice-daily in the open-label treatment phases, and simufilam or matching placebo during the randomized withdrawal phase.

All study participants who completed 12 months of open-label simufilam treatment were eligible to participate in the 6-month randomized, placebo-controlled withdrawal phase. Likewise, all study participants who completed the randomized, placebo-controlled withdrawal phase were eligible for 6 additional months of open-label treatment. Alzheimer?s is a degenerative disease of the brain.

Over time, a patient?s cognition progressively worsens as the disease takes its toll. The science literature suggests that patients with mild Alzheimer?s decline by a group average of approximately 3 points per year on the ADAS-Cog scale. With disease progression, patients move from mild to moderate to, eventually, severe Alzheimer?s disease.

Cognitive decline becomes more pronounced, and presumably more difficult to treat, in advanced stages of the disease. Patients with mild Alzheimer?s disease (n=87) entered the open-label study with MMSE 21-26, with ten exceptions.2 Patients with moderate Alzheimer?s entered the open-label study with MMSE 16-20, with one patient who entered with MMSE 15. Mild patients who received simufilam for 24 continuous months (n=47) showed an average change of 0.07 points on ADAS-Cog11 (± 1.51 SE), baseline to month 24, as a group.

Mild Alzheimer?s patients who received 12 months of open-label simufilam, followed by placebo in the 6-month randomized, placebo-controlled withdrawal phase, followed by an additional 6 months of open-label simufilam (n=40), declined by an average of 1.04 points on ADAS-Cog11 (± 1.65 SE), baseline to month 24, as a group.