Cassava Sciences, Inc. (Nasdaq: SAVA) announced top-line clinical
data today from a pre-planned interim analysis of an on-going
open-label study with its drug candidate simufilam in patients with
mild-to-moderate Alzheimer’s disease.
In a study funded by the National Institutes of
Health (NIH), ADAS-Cog11 scores improved an average of 3.2 points
from baseline (p<0.001) in the first 50 study subjects who
completed 12 months of open-label treatment with simufilam. To
emphasize impartiality, changes in ADAS-Cog scores baseline to
month 12 were independently analyzed by two consulting
biostatisticians.
“I feel energized and encouraged by the clinical
data,” said Remi Barbier, President & CEO. “We look forward to
the initiation of a randomized, double-blind, placebo-controlled
pivotal Phase 3 clinical program with simufilam in people with
Alzheimer’s disease.”
Response Analysis
In the first 50 study subjects who completed 12
months of open-label treatment with simufilam:
- ADAS-Cog11 scores improved an
average of 3.2 points from baseline (S.D. ± 6.3; p<0.001)
- 68% of study subjects improved on
ADAS-Cog at 12 months; these study subjects improved an average of
6.8 points (S.D. ± 3.8)
- An additional 20% of study subjects
declined less than 5 points on ADAS-Cog at 12 months; these study
subjects declined an average of 2.5 points (S.D. ± 1.3)
An independent, published meta-analysis of
patients with mild-to-moderate Alzheimer’s disease reports an
average decline of 5.5 points over 12 months1 amongst study
subjects who were administered placebo in randomized, controlled
trials.
Study subjects entered the open-label study with
a clinical diagnosis of mild-to-moderate Alzheimer’s, Mini-Mental
State Examination (MMSE) range 16-26.
Safety Analysis
Drug is well-tolerated. There are no
drug-related serious adverse events through the 12-month interim
analysis.
Chain of Custody for Clinical
Data
Investigator sites collect clinical data from
study subjects. Sites enter their clinical data directly into an
electronic data capture (EDC) system managed by an outside data
management vendor. The data management vendor also maintains the
clinical database. At Cassava Sciences’ request, the data
management vendor transmitted baseline and month-12 ADAS-Cog scores
directly to two independent consulting biostatisticians for
analysis. Both consultants hold PhD’s in statistics and provide
consulting expertise in support of medical research. One consultant
is based in Texas, the other in Arizona. Both statisticians
independently reached the same statistical conclusions on changes
in ADAS-Cog scores, baseline to month 12.
Neuropsychiatric Inventory (NPI) at the
12 Month Interim Analysis
Alzheimer’s is often accompanied by behaviors
disorders, such as anxiety, agitation or delusions. These may
become more frequent as disease progresses. The Neuropsychiatric
Inventory (NPI) is a clinical tool widely used to measure changes
in dementia-related behavior. At baseline, 34% of these study
subjects had no neuropsychiatric symptoms on the NPI. At 12 months,
over 50% had no neuropsychiatric symptoms on the NPI.
Clinical Strategy Around Open-label
Study
Long-term safety data is a regulatory
requirement. To collect these data, some drug development companies
conduct an open-label study at the conclusion of a Phase 3 clinical
testing program. Cassava Sciences believes it is prudent to conduct
an open-label study before undertaking a large, complex and
expensive Phase 3 clinical program in Alzheimer’s disease: if an
experimental drug for Alzheimer’s fails to show long-term safety or
any treatment benefit in a large, well-designed, open-label study,
such drug is unlikely to succeed under the more rigorous conditions
of a randomized, controlled trial. However, treatment effects
observed in an open-label study are not proof of drug safety or
efficacy, nor can open-label data predict clinical success in a
Phase 3 program. Proof of safety and efficacy will always rest on
results of a randomized, double-blind, placebo-controlled pivotal
Phase 3 clinical program, which has not yet been conducted with
simufilam.
About the Open-label Study
In March 2020, Cassava Sciences initiated a
long-term, open-label study to evaluate simufilam in patients with
Alzheimer’s disease. This study is funded by a research grant award
from the National Institutes of Health (NIH). The open-label study
is intended to monitor the long-term safety and tolerability of
simufilam 100 mg twice-daily for 12 or more months. Another study
objective is to measure changes in cognition using ADAS-Cog and to
assess the presence and severity of dementia-related behavior using
the Neuropsychiatric Inventory (NPI). Approximately 200 study
subjects are now enrolled in the open-label study from 16
investigator sites in the U.S and Canada. The study’s dropout rate
is currently under 10%.
Next Step: Phase 3 Clinical Program
under FDA Special Protocol
Assessments
Cassava Sciences is advancing simufilam into a
Phase 3 clinical program in Alzheimer’s disease. Study initiation
is on-track for Q4 2021. On August 24, 2021, Cassava Sciences
announced it had reached agreement with the U.S. Food and Drug
Administration (FDA) under a Special Protocol Assessment (SPA) for
both of its Phase 3 studies.
About Simufilam
Simufilam (sim-uh-FILL-am) is a proprietary,
small molecule (oral) drug that restores the normal shape and
function of altered filamin A (FLNA), a scaffolding protein, in the
brain. Altered FLNA in the brain disrupts the normal function of
neurons, leading to Alzheimer’s pathology, neurodegeneration and
neuroinflammation. The underlying science for simufilam is
published in peer-reviewed journals, including Journal of
Neuroscience, Neurobiology of Aging, Journal of Biological
Chemistry, Neuroimmunology and Neuroinflammation and Journal
of Prevention of Alzheimer’s Disease. Simufilam is substantially
supported by peer-reviewed research grant awards from the National
Institutes of Health (NIH).
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’ mission is to discover and
develop innovations for chronic, neurodegenerative conditions. Over
the past 10 years, Cassava Sciences has combined state-of-the-art
technology with new insights in neurobiology to develop novel
solutions for Alzheimer’s disease. For more information, please
visit: https://www.CassavaSciences.com.
For More Information
Contact:
Eric Schoen, Chief Financial
Officereschoen@CassavaSciences.com(512) 501-2450
Cautionary Note Regarding
Forward-Looking Statements: This press release includes
forward looking statements including but not limited to those
regarding the timing of the initiation of our pivotal Phase 3
program with simufilam in Alzheimer’s disease and its likelihood of
success, the interpretation of clinical data generated in a
12-month interim analysis of an open-label study, the clinical
safety profile of simufilam, the occurrence of neuropsychiatric
symptoms in people with Alzheimer’s disease, the publication of an
analysis regarding the expected rate of cognitive decline in people
with Alzheimer’s disease and oral or written comments made by our
employees regarding simufilam and its clinical development.
Drug development involves a high degree of risk,
and historically only a small number of research and development
programs result in commercialization of a product. Clinical results
from our earlier-stage clinical trials may not be indicative of
full 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 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 initiation, conduct or completion of our
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 December 31, 2020 and future
reports to be filed with the SEC. The foregoing sets forth many,
but not all, of the factors that could cause actual results to
differ from expectations in any forward-looking statement. In light
of these risks, uncertainties and assumptions, the forward-looking
statements and events discussed in this news release are inherently
uncertain and may not occur, and actual results could differ
materially and adversely from those anticipated or implied in the
forward-looking statements. Accordingly, you should not rely upon
forward-looking statements as predictions of future events. Except
as required by law, we disclaim any intention or responsibility for
updating or revising any forward-looking statements contained in
this news release.
The content of this press release is solely our
responsibility and does not represent the official views of the
National Institutes of Health (NIH).
For further information regarding these and
other risks related to our business, investors should consult our
filings with the SEC, which are available on the SEC's website at
www.sec.gov.
1 Disease Progression Meta-analysis Model in Alzheimer’s disease
(Ito, et al., Pfizer Global Research), Alzheimer’s & Dementia 6
(2010) 39-53
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