Cassava Sciences Announces Positive Top-Line Clinical Results in Phase 2 Study Evaluating Simufilam in Alzheimer’s Disease
- ADAS-Cog mean scores changed minimally over 1 year in patients with mild-to-moderate Alzheimer’s disease treated with open-label simufilam tablets.
- 47% of patients improved on ADAS-Cog over 1 year, and this group improved by 4.7 points. An additional 23% of patients declined less than 5 points on ADAS-Cog over 1 year, and this group declined by 2.5 points.
- Mild patients responded better than patients with moderate Alzheimer’s disease.
- Simufilam was safe, well tolerated.
Top-line Results – mean scores, baseline to month 12 (lower is better, except for MMSE):
- ADAS-Cog11 scores changed from 19.1 (±9.2) to 19.6 (±13.3)
- MMSE scores changed from 21.5 (±3.6) to 20.2 (±6.4)
- NPI10 scores changed from 3.2 (±4.6) to 2.9 (±4.6)
- GDS scores changed from 1.8 (±1.8) to 1.4 (±1.9)
Alzheimer’s is a degenerative disease of the brain. Over time, cognition progressively worsens in the mild-to-moderate stages of Alzheimer’s as the disease takes its toll. ADAS-Cog scores that change minimally (or improve) over 1 year is a highly desirable outcome in a clinical study of mild-to-moderate Alzheimer’s disease.
Figure 1 presents a model of historical declines on ADAS-Cog in patients with mild-to-moderate Alzheimer’s disease.
Figure 1: Statistical model of historical 1-year declines on ADAS-Cog, placebo vs simufilam treatment, mild-to-moderate disease.1
Response Analysis – baseline to month 12
- ADAS-Cog scores improved in 47% of patients; this group had a mean change of -4.7 (±3.8) points (lower is better).
- In an additional 23% of patients, ADAS-Cog declined less than 5 points; this group had a mean change of 2.5 (±1.4) points.
- Patients with an NPI10 score of zero increased from 42% to 54%, indicating reduced dementia-related neuropsychiatric symptoms.
“I’m very excited about these 1-year data,” said
Analysis of Efficacy Endpoints
Efficacy outcomes were analyzed by an independent, outside biostatistical consulting firm led by
Alzheimer’s is a progressive disease. Severity of disease is typically assessed by MMSE score. In this study, mild patients are MMSE 21-26; moderate patients are MMSE 16-20. Mild and moderate sub-groups showed notable differences on changes in ADAS-Cog mean scores, baseline to month 12 (lower is better):
- In the mild sub-group, ADAS-Cog scores improved, from 15.0 (±6.3) to 12.6 (±7.8)
- In the moderate sub-group, ADAS-Cog scores worsened, from 25.7 (±9.2) to 30.1 (±13.1)
“The data for simufilam are noteworthy,” said
Figure 2 presents a model of historical declines on ADAS-Cog in early disease and mild disease.
Figure 2: Statistical model of historical 1-year declines on ADAS-Cog, placebo vs simufilam treatment, in early disease and mild disease.2
Simufilam 100 mg twice daily was safe and well tolerated. There were no drug-related serious adverse events. Three treatment-emergent adverse events (TEAEs) occurred in 7% or more of study patients: COVID-19 (12%), urinary tract infection (10%) and headache (9%). Reported TEAEs are based on all study patients who received at least one dose of drug. The top three reasons for patient discontinuations were withdrawal of informed consent (N=14), adverse events (N=13) and patient non-compliance (N=7).
‘Research use only’, non-safety, exploratory biomarkers were analyzed from cerebrospinal fluid (CSF) collected from 25 patients in the open-label study who agreed to undergo a lumbar puncture at baseline and again after 6 months of treatment. CSF samples were analyzed blind by our academic collaborator at
- CSF biomarkers of disease pathology, t-tau and p-tau181, decreased 38% and 18%, respectively (both p<0.00001).
- CSF biomarkers of neurodegeneration, neurogranin and neurofilament light chain (NfL), decreased 72% and 55%, respectively (both p<0.00001).
- CSF biomarkers of neuroinflammation, sTREM2 and YKL-40, decreased 65% and 44% (both p<0.00001).
Of the 25 patients who provided 6-month CSF samples, 24 subsequently completed 1 year of treatment with open-label simufilam. This sub-set of patients improved -4.96 mean points on ADAS-Cog from baseline to month 12 (ad hoc analysis conducted internally; lower is better). We have not conducted further CSF sample analyses in the open-label study.
Chain of Custody for Clinical Data
Investigator sites collected clinical data from study patients. Sites entered their clinical data directly into an electronic data capture system managed by an independent, outside data management vendor. The data management vendor also maintains the clinical database. The data management vendor transmitted the clinical database directly to
Data results from our open-label safety study do not constitute, and should not be interpreted as, regulatory evidence of safety or efficacy for simufilam in Alzheimer’s disease. Rigorous evidence for drug safety and efficacy is derived from one or more large, randomized, placebo-controlled studies. The open-label design and size of this study may introduce clinical or statistical bias or may generate results that may not fully distinguish between drug effects and random variation. Different methods of statistical analysis on 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 study’s findings prior to us receiving the final dataset. Final data may change from today’s top-line data. We expect to disclose the final dataset in a future medical conference or science publication.
On-going Phase 3 Studies with 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.
For more information, please visit: https://www.CassavaSciences.com
For More Information Contact:
(512) 501-2450, or eschoen@CassavaSciences.com
Cautionary Note Regarding Forward-Looking Statements:
This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to: our current expectations regarding the target patient enrollment numbers for our Phase 3 studies; our goals regarding timing for releasing top-line data for the Cognition Maintenance Study; comments made by our employees regarding simufilam and the treatment of Alzheimer’s disease; and potential benefits, if any, of our product candidates. These statements may be identified by words such as “may,” “anticipate,” “believe,” “could,” “expect,” “would”, “forecast,” “intend,” “plan,” “possible,” “potential,” and other words and terms of similar meaning.
Drug development involves a high degree of risk, and only a small number of research and development programs result in regulatory approval and commercialization of a product. Our interim data and analyses should not be relied upon as predictive of full study results for any of our studies. Our clinical results from earlier-stage clinical trials may not be indicative of full study results, or results from later-stage, or larger scale clinical trials, and do not ensure regulatory approval. You should not place undue reliance on these statements or any scientific data we present or publish.
Such statements are based largely on our current expectations and projections about future events. Such statements speak only as of the date of this news release and are subject to a number of risks, uncertainties and assumptions, including, but not limited to, those risks relating to the ability to conduct or complete clinical studies on expected timelines, to demonstrate the specificity, safety, efficacy or potential health benefits of our product candidates, the severity and duration of health care precautions given the COVID-19 pandemic, any unanticipated impacts of the pandemic on our business operations, and including those described in the section entitled “Risk Factors” in our Annual Report on Form 10-K for the year ended
1 Figure 1: Forest plot meta-analysis model by
2 Figure 2: Forest plot meta-analysis model by
3 Statistical analysis on changes in CSF biomarkers was conducted internally; press release is available on-line: https://www.cassavasciences.com/node/15486/pdf.
Photos accompanying this announcement are available at
Source: Cassava Sciences, Inc.