Cassava Sciences, Inc. (Nasdaq: SAVA), a biotechnology company
developing product candidates for Alzheimer’s disease, today
announced the successful completion of an End-of-Phase 2 (EOP2)
meeting with the U.S. Food and Drug Administration (FDA) for
simufilam, its lead drug candidate for the treatment of Alzheimer’s
disease. Official EOP2 meeting minutes indicate FDA and Cassava
Sciences agree on key elements of a pivotal Phase 3 clinical
program in support of a New Drug Application (NDA) filing for
simufilam in Alzheimer’s disease. Agreements reached during the
EOP2 meeting show a clear path forward for advancing simufilam into
Phase 3 studies in the second half of 2021.
“For over 10 years we’ve been doing basic
research and early drug development with simufilam,” said Remi
Barbier, President & CEO. “We are excited to finally advance
simufilam into pivotal Phase 3 clinical studies in people with
Alzheimer’s disease. We believe the underlying science is solid,
the drug appears safe and the clinical roadmap makes sense. We’ve
crossed the Rubicon.”
“We appreciate the valuable guidance and
flexibility FDA has provided,” added Jim Kupiec, MD, Cassava
Sciences’ Chief Clinical Development Officer. “We look forward to
continuing a collaborative dialogue throughout the pivotal Phase 3
clinical development program.”
Simufilam is a novel drug, discovered at Cassava
Sciences, that targets both neuroinflammation and
neurodegeneration. The EOP2 meeting discussion was supported by
years of scientific and clinical data, including positive results
from a previously completed Phase 2 clinical program with simufilam
in Alzheimer’s disease. In a double-blind, randomized,
placebo-controlled Phase 2b study, simufilam demonstrated robust
effects on primary and secondary outcome measures, with no safety
issues. Recently, the Company announced that simufilam improved
cognition in subjects with Alzheimer’s disease in a 6-month interim
analysis of an open-label study, with no safety issues.
The EOP2 meeting took place mid-January. FDA
attendees included Robert Temple, MD, Deputy Center Director for
Clinical Science and Senior Advisor in the Office of New Drugs;
Billy Dunn, MD, Director, Office of Neuroscience; Eric Bastings,
MD, Director, Division of Neurology, and others.
Official meeting minutes confirm that Cassava
Sciences and FDA are aligned on key elements of a Phase 3 clinical
program for simufilam. FDA has agreed that the completed Phase 2
program, together with an upcoming and well-defined Phase 3
clinical program, are sufficient to show evidence of clinical
efficacy for simufilam in Alzheimer’s disease. There is also
agreement that the use of separate clinical scales to assess
cognition (ADAS-cog1) and function (ADCS-ADL2) are appropriate
co-primary endpoints of efficacy. A clinical scale that combines
cognition and function, such as iADRS3, is a secondary efficacy
endpoint.
Cassava Sciences’ pivotal Phase 3 clinical
program consists of two double-blind, randomized,
placebo-controlled studies, each described below.
Cassava Sciences’ first Phase 3 study is
designed to evaluate disease-modifying effects of simufilam in
Alzheimer’s disease. The goal is to demonstrate a slower rate of
decline in cognition and health function in subjects treated with
simufilam compared to placebo.
Details of the first Phase 3 study include:
- Approximately 1,000 subjects with
mild-to-moderate Alzheimer’s disease to be enrolled.
- Subjects to be randomized (1:1:1)
to simufilam 100 mg, 50 mg, or placebo BID.
- Subjects to be treated for 18
months.
- The co-primary efficacy endpoints
are ADAS-Cog, a cognitive scale, and ADCS-ADL, a functional scale;
both are widely used clinical tools in trials of Alzheimer’s
disease.
- A secondary efficacy endpoint is
iADRS, a widely used clinical tool in trials of Alzheimer’s disease
that combines cognitive and functional scores from ADAS-Cog &
ADCS-ADL.
- Other secondary endpoints include
biomarkers of disease and NPI4, a clinical tool that assesses the
presence and severity of dementia-related behavior.
- The Company plans to initiate the
first pivotal Phase 3 study Q3 2021.
Cassava Sciences’ second Phase 3 study is
designed to evaluate symptomatic improvement in Alzheimer’s
disease. The goal is to demonstrate improved cognition and health
function in subjects treated with simufilam compared to
placebo.
Details of the second Phase 3 study include:
- Approximately 600 subjects with
mild-to-moderate Alzheimer’s disease to be enrolled.
- Subjects to be randomized (1:1) to
simufilam 100 mg or placebo BID.
- Subjects to be treated for 9 to 12
months.
- The co-primary efficacy endpoints
are ADAS-Cog, a cognitive scale, and ADCS-ADL, a functional scale;
both are widely used clinical tools in trials of Alzheimer’s
disease.
- A secondary efficacy endpoint is
iADRS, a widely used clinical tool in trials of Alzheimer’s disease
that combines cognitive and functional scores from ADAS-Cog &
ADCS-ADL.
- Other secondary endpoints include
biomarkers of disease and NPI, a clinical tool that assesses the
presence and severity of dementia-related behavior.
- The Company plans to initiate the
second pivotal Phase 3 study Q4 2021.
FDA has provided further flexibility to Cassava
Sciences by agreeing to review the final version of each protocol
for the two Phase 3 studies, and to conduct a Special Protocol
Assessment (SPA) for each Phase 3 study. An SPA is a formal
regulatory procedure that confirms certain critical details of a
Phase 3 study protocol, such as the statistical analyses, meet
FDA’s standards of approvability.
In addition to the planned pivotal Phase 3
clinical program, other clinical studies in support of simufilam’s
safety and efficacy in Alzheimer’s disease are briefly described
below.
Open-label StudyCassava
Sciences recently expanded the size of an ongoing open-label study
of simufilam. The study’s target enrollment was increased by up to
50 additional subjects with mild-to-moderate Alzheimer’s disease,
for a total target enrollment of up to 150 subjects. To accommodate
increased enrollment, the Company is opening new clinical sites in
the U.S. and Canada.
The Company plans to conduct a second interim
analysis of the open-label study mid-year 2021, when approximately
50 subjects complete 12 months of drug treatment. Much like the
first pre-planned interim analysis (6 months), the second
pre-planned interim analysis (12 months) is expected to generate
clinical data around long-term safety, cognition and
dementia-related behavior.
Cognition Maintenance Study
(CMS)In Q2 2021, Cassava Sciences plans to initiate a
double-blind, randomized, placebo-controlled study in subjects with
Alzheimer’s disease who have completed at least one year of
open-label treatment with simufilam. In this Cognition Maintenance
Study (CMS), subjects who complete one year of open-label treatment
will be randomized (1:1) to simufilam or placebo for 6 months. The
CMS is designed to compare simufilam’s effects on cognition and
dementia-related in subjects who continue with drug treatment
versus those who discontinue drug treatment. For ethical and other
reasons, subjects who successfully complete the 6-month CMS will be
given the option to return to open-label simufilam again.
Slide DeckCassava Sciences’
latest corporate presentation is available on its website under the
Investors/Presentations page: https://www.CassavaSciences.com
About Alzheimer's Disease
Alzheimer’s disease is a progressive brain disorder that destroys
memory and thinking skills. Currently, there are no drug therapies
to halt Alzheimer’s disease, much less reverse its course. As of
2020, there were approximately 50 million people worldwide living
with dementia, a figure expected to increase to 150 million by
2050.5 The annual global cost of dementia is now above $1 trillion,
according to Alzheimer’s Disease International, a charitable
organization.
About SimufilamSimufilam 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. Cassava Sciences is also
developing an investigational diagnostic, called SavaDx, to detect
Alzheimer’s disease with a simple blood test.
Simufilam and SavaDx were both developed
in-house. Both product candidates are substantially funded by
peer-review 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
Cassava Sciences Safe
HarborThis 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 strategy and plans; the treatment of Alzheimer’s
disease; the status of current and future clinical studies with
simufilam, including the interpretation of an interim analysis of
an open-label study and Phase 2 program results; plans to conduct a
second interim analysis of an open-label study and the timing
thereof; planned enrollment and other changes to said open-label
program; results of our EOP2 meeting with FDA including agreement
on elements to support a New Drug Application filing for simufilam
in Alzheimer’s disease; our intention to initiate a Phase 3
clinical program with simufilam and the timing, enrollment,
duration and other details thereof; verbal commentaries made by our
employees; and potential benefits, if any, of the our product
candidates. These statements may be identified by words such as
“may,” “anticipate,” “believe,” “could,” “expect,” “forecast,”
“intend,” “plan,” “possible,” “potential,” and other words and
terms of similar meaning. Drug development and commercialization
involve a high degree of risk, and only a small number of research
and development programs result in commercialization of a product.
Our clinical results from 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 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 December 31, 2019 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. 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.
This press release also contains information
based on independent industry publications. We have not
independently verified the accuracy or completeness of the
information contained in these publicly available sources.
Accordingly, we make no representations as to the accuracy or
completeness of such information. You are cautioned not to give
undue weight to such information.
1 ADAS-Cog = The Alzheimer’s Disease Assessment Scale –
Cognitive Subscale, a measure of cognition 2 ADCS-ADL = Alzheimer’s
Disease Cooperative Study – Activities of Daily Living, a measure
of health function3 iADRS = integrated Alzheimer’s Disease Rating
Scale, a composite measure of cognition and health function4
Neuropsychiatric Inventory (NPI)5 Alzheimer's Disease
International, Dementia Statistics, available on-line and accessed
February 20, 2021:
https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/
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