AUSTIN, Texas — Cassava Sciences, Inc. (Nasdaq: SAVA), a biotechnology company, today 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.
“We’re fighting Alzheimer’s disease by testing simufilam, a new type of drug that has a completely different mechanism of action from monoclonal antibody drug treatments,” said Remi Barbier, President & CEO. “Stable ADAS-Cog scores over 2 years is clearly a desirable clinical outcome in Alzheimer’s. Our data in mild patients may emphasize the importance of treating patients early in the disease.”
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 phase, 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. 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.
Mean ADAS-Cog scores at baseline were approximately balanced in the group of mild Alzheimer’s patients who received drug continuously versus non-continuously (15.2 and 14.6, respectively).
Safety Data
Oral simufilam 100 mg tablets twice daily appeared safe and well tolerated in this study. There were no drug-related serious adverse events. The most common treatment-emergent adverse events (TEAEs) were Covid-19 and urinary tract infection, with 33 occurrences of each.
Efficacy Data Presentation
The pre-specified cognition endpoints were analyzed on the Full Analysis Set (FAS) by Pentara Corporation, an independent consulting firm that specializes in complex statistical analysis of clinical trial results. Suzanne Hendrix, PhD, CEO of Pentara, has over 150 peer-reviewed publications of clinical trial results and statistical approaches for clinical trials, many focusing on statistical methodology for Alzheimer’s disease.
We expect to report data from the two-year clinical safety study in a science forum.
Study Limitations
Data results from our two-year open-label safety study, or any phase thereof, do not constitute, and should not be interpreted as, regulatory evidence of safety or efficacy for simufilam in Alzheimer’s disease dementia. Rigorous evidence for drug safety and efficacy is derived from one or more large, randomized, placebo-controlled studies. The open-label design and limited size of this study, and each sub-group of this study, may introduce clinical or statistical bias or may generate results that may not fully distinguish between drug effects and random variation. In addition, we do not know how long a washout period may be needed to remove lingering drug effects, if any, from prior treatment with open-label simufilam. Different methods of statistical analysis of clinical data from the same study may lead to objectively different numerical results. These and other statistical and clinical features of our open-label study add complexity or limitations to the scope of data interpretation.
‘Top-line data’ is a summary of the clinical data prior to the completion of a full and final audit or quality-control of the clinical database. We are communicating top-line data so that stakeholders may have timely access to a summary of the open-label study findings prior to us receiving the final dataset. Final data may change from top-line data.
On-going Phase 3 Studies of Simufilam in Alzheimer’s Disease
Cassava Sciences is evaluating oral simufilam for Alzheimer’s disease dementia in two global Phase 3 clinical studies, both of which are fully enrolled. A total of 1,929 patients with mild-to-moderate Alzheimer’s disease dementia who met study eligibility criteria were randomized into the Phase 3 program from sites in the U.S., Puerto Rico, Canada, Australia and South Korea.
The first Phase 3 trial (NCT04994483) has a 52-week treatment period; 804 Alzheimer’s patients were randomized into this study. Top-line results for the 52-week Phase 3 study are expected approximately year-end 2024.
The second Phase 3 trial (NCT05026177) has a 76-week treatment period; 1,125 Alzheimer’s patients were randomized into this study. Top-line results for the 76-week Phase 3 study are expected approximately mid-year 2025.
About Simufilam
Simufilam is Cassava Sciences’ proprietary, small molecule (oral) drug candidate that restores the normal shape and function of altered filamin A (FLNA) protein in the brain. Cassava Sciences owns worldwide development and commercial rights to its research programs in Alzheimer’s disease, and related technologies, without royalty obligations to any third party.
About Cassava Sciences, Inc.
Cassava Sciences is a clinical-stage biotechnology company based in Austin, Texas. Our mission is to detect and treat neurodegenerative diseases, such as Alzheimer’s disease. Our product candidates have not been approved by any regulatory authority, and their safety, efficacy or other desirable attributes have not been established in humans.
Contact:
Eric Schoen, Chief Financial Officer
(512) 501-2450
[email protected]