Cassava Sciences, Inc. (Nasdaq: SAVA) today announced additional
clinical data of a Phase 2b study with sumifilam, its lead drug
candidate, in patients with Alzheimer’s disease. In a clinical
study funded by the National Institutes of Health (NIH), sumifilam
decreased levels of a protein called HMGB1 and improved
measurements of the integrity of the blood-brain barrier (BBB). The
ability of a drug candidate to decrease HMGB1 and improve BBB
integrity in patients with Alzheimer’s disease has not been
previously reported in the science literature. Sumifilam is a
proprietary, small molecule (oral) drug that restores the normal
shape and function of altered filamin A protein in the brain.
“The ability to improve multiple biomarkers of
disease with one drug is a unique achievement,” said Remi Barbier,
President & CEO of Cassava Sciences. “We believe these exciting
clinical results create a time of rapid strategic momentum for the
Company, to include development plans to evaluate sumifilam in a
Phase 3 clinical program in patients with Alzheimer’s disease.”
Additional Phase 2b Study
ResultsAdditional clinical data include changes in levels
of HMGB1 protein and measurements of the integrity of the
blood-brain barrier from baseline to Day 28 (all p-values versus
placebo):
Sumifilam Significantly
Reduced Levels of HMGB1
in Cerebrospinal Fluid
(CSF):
- HMGB1 decreased 33% (p<0.001) in
patients treated with 50 mg sumifilam
- HMGB1 decreased 32% (p<0.001) in
patients treated with 100 mg sumifilam
Sumifilam Significantly
Improved the Integrity of the
Blood-brain
Barrier (BBB):
- CSF IgG decreased 30% (p<0.05)
in patients treated with 50 mg sumifilam
- CSF IgG decreased 30% (p<0.05)
in patients treated with 100 mg sumifilam
- CSF albumin decreased 15%
(p<0.05) in patients treated with 50 mg sumifilam
- CSF albumin decreased 28%
(p<0.05) in patients treated with 100 mg sumifilam
Sumifilam
Improved the Albumin
Ratio, a Test
of
Blood-brain
Barrier
(BBB)
Permeability:
- BBB permeability can be clinically
evaluated by comparing levels of albumin in CSF and plasma. The
albumin ratio is a test for BBB permeability because albumin
protein is not synthesized in CSF. Hence, albumin in CSF
necessarily comes from plasma through the BBB. The albumin ratio is
frequently elevated in patients with dementia and various other
disorders.
- In the Phase 2b study, the albumin
ratio was unchanged for Alzheimer’s patients on placebo. The
albumin ratio improved by approximately 5 and 7 points for patients
treated with sumifilam, 50 mg and 100 mg, respectively, over 28
days.
Changes
in the Albumin Ratio by
Treatment Group
Treatment |
Day 0 |
Day 28 |
Change-Day 0 to 28 |
Placebo |
24 |
24 |
No change |
50 mg sumifilam |
25 |
20 |
- 5 |
100 mg sumifilam |
25 |
18 |
- 7 |
About HMGB1HMGB1 is an
endogenous and potent pro-inflammatory protein that is sometimes
called a ‘danger molecule.’ HMGB1 is elevated in patients with
Alzheimer’s disease and other neurodegenerative disorders and many
other disorders. Elevated levels of HMGB1 induce neuroinflammation,
tissue damage and, eventually, cell death. Preclinical research has
shown that inhibiting HMGB1 improves outcomes in neurodegenerative
disease models, decreasing neuroinflammation and improving learning
and memory. PubMed® reports nearly 6,000 scientific publications of
HMGB1 research in the past decade, highlighting the molecule’s
potential importance in clinical research.
About the
Blood-brain
Barrier (BBB)The BBB is a complex border of cells
along blood vessels that prevent unwanted substances in blood from
entering the brain. BBB integrity is essential to brain health. A
healthy BBB system selectively allows the passage of some molecules
into the brain, such as water and glucose, while blocking passage
to molecules that may damage the brain. Levels of IgG antibodies
and albumin protein in the cerebrospinal fluid (CSF) are an index
of BBB integrity, with elevated levels evidence of a ‘leaky’,
impaired BBB. Albumin protein is found at high levels in plasma and
low levels in CSF because it does not normally cross the BBB.
Late-breaking Presentation at CTAD
2020Clinical results of a Phase 2b study of sumifilam were
selected as a late-breaking oral presentation by the 13th
international conference on Clinical Trials on Alzheimer’s Disease
(CTAD). CTAD is a prestigious annual conference focused on
Alzheimer’s clinical research and takes place this year as a
virtual event on November 4-7th, 2020.
On Saturday, November 7th, Company scientists
will present an oral presentation titled, “Sumifilam Significantly
Improves Eleven CSF Biomarkers in a Randomized, Placebo-Controlled,
One-Month Clinical Trial in Alzheimer’s Disease
Patients.”
The Company’s CTAD presentation is available on
its website: https://www.CassavaSciences.com
Phase 2b
Study DesignPhase 2b was a double-blind,
randomized, placebo-controlled, multi-center clinical study of
sumifilam (formerly, PTI-125). Sixty-four patients with
mild-to-moderate Alzheimer’s disease, age 50-85, were randomized
(1:1:1) to 100 mg or 50 mg oral sumifilam or matching placebo.
Treatment was administered twice daily for 28 days. Nine U.S. study
sites enrolled patients. A clinical diagnosis of Alzheimer’s
disease was confirmed with the Mini-Mental State Examination (MMSE)
≥16 to ≤26 and a CSF T-tau/Aβ42 ratio ≥0.28. Safety was assessed by
ECGs, clinical labs, adverse event monitoring and physical
examinations.
Previously Announced Clinical Phase 2b
DataAs previously announced in September 2020, sumifilam
was safe and well-tolerated, with no drug-related patient
discontinuations. Alzheimer’s patients treated with 50 mg or 100 mg
sumifilam twice-daily for 28 days showed statistically significant
(p<0.05) improvements in eight biomarkers of disease pathology,
neurodegeneration and neuroinflammation, versus Alzheimer’s
patients who took placebo. In addition, Alzheimer’s patients
treated with sumifilam showed improvements in validated tests of
Episodic Memory and Spatial Working Memory, versus patients who
took placebo (Effect Sizes 17-46%). Cognitive improvements
correlated most strongly (R2=0.5) with decreases in P-tau181, a
biomarker that leads to tangles in the brain. Sumifilam decreased
brain levels of Ptau-181 by 8-11%, versus placebo. The study
achieved a 98% response rate, defined as the proportion of study
participants taking sumifilam who showed improvements in
biomarkers.
On-going
Open-label
StudyIn March 2020, we announced the initiation of
an open-label study to evaluate sumifilam in patients with
Alzheimer’s disease. This is an open-label, multi-center, extension
study to monitor the long-term safety and tolerability of sumifilam
100 mg twice-daily for 12 months. The study’s target enrollment is
approximately 100 patients with mild-to-moderate Alzheimer’s
disease. This study has exceeded 60% enrollment. The open-label
study employs The Alzheimer's Disease Assessment Scale-Cognitive
Subscale (ADAS-Cog-11) to assess cognitive symptoms of dementia and
The Neuropsychiatric Index (NPI) to assess behavioral symptoms.
Cassava Sciences plans to announce results of an interim analysis
as additional safety and cognition data is collected from patients
enrolled in the open-label study.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. In the U.S. alone, approximately 5.8 million
people are currently living with Alzheimer’s disease, and
approximately 487,000 people age 65 or older developed Alzheimer’s
in 2019.1 The number of people living with Alzheimer’s disease is
expected to grow dramatically in the years ahead, resulting in a
growing social and economic burden.2
About SumifilamSumifilam 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
sumifilam 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. The Company is also developing
an investigational diagnostic, called SavaDx, to detect Alzheimer’s
disease with a simple blood test.
Sumifilam 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. Patent protection in this area runs through 2037, plus
extensions, and includes seven issued patents and related patent
filings and applications.
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 OfficerCassava
Sciences, Inc.eschoen@CassavaSciences.com(512) 501-2450
Cassava Sciences’ Phase
2b study of sumifilam in Alzheimer’s disease was funded by clinical
research grant #AG060878 from the National
Institutes of Health (NIH/NIA).
The content of this press release is solely the
responsibility of Cassava Sciences and does not necessarily
represent the official views of the
NIH/NIA.
Cautionary Note Regarding
Forward-Looking Statements: This press release contains
“forward-looking statements” for purposes of the Private Securities
Litigation Reform Act of 1995 (the Act). Cassava Sciences claims
the protection of the Safe Harbor for forward-looking statements
contained in the Act. All statements other than statements of
historical fact contained in this press release including, but not
limited to, statements regarding the status of current and
future clinical studies with sumifilam, including our intention to
conduct a Phase 3 clinical program; the interpretation of results
of our Phase 2 clinical studies including cognition data; plans to
announce results of an interim analysis of an ongoing open-label
study; potential health benefits, if any, of changes in levels of
biomarkers; verbal commentaries made by Cassava Sciences’
employees; and potential benefits, if any, of the Company’s product
candidates for Alzheimer’s disease are forward-looking
statements. Such statements are based largely on the Company’s
current expectations and projections about future events. Such
statements speak only as of the date of this press 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 Cassava Sciences’ Annual Report on Form 10-K for the
year ended December 31, 2019 and future reports to be filed with
the SEC. In light of these risks, uncertainties and assumptions,
the forward-looking statements and events discussed in this press
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, the
Company disclaims any intention or responsibility for updating or
revising any forward-looking statements contained in this press
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.
1,2 Source: Alzheimer’s Association. 2019
Alzheimer’s Disease Facts and Figures. Available online at:
https://www.alz.org/media/documents/alzheimers-facts-and-figures-2019-r.pdf
Cassava Sciences (NASDAQ:SAVA)
Historical Stock Chart
From Mar 2024 to Apr 2024
Cassava Sciences (NASDAQ:SAVA)
Historical Stock Chart
From Apr 2023 to Apr 2024