Three poster presentations highlight the role
of NMDA receptor dysfunction in Huntington’s Disease related
cognitive impairment and potential for positive cognitive effects
with SAGE-718
Sage Therapeutics (NASDAQ: SAGE), a biopharmaceutical company
committed to developing novel therapies with the potential to
transform the lives of people with debilitating disorders of the
brain, today announced that it plans to advance SAGE-718, a novel,
first-in-class, oxysterol-based positive allosteric modulator (PAM)
of N-methyl-D-aspartate (NMDA) receptors, to a Phase 2
placebo-controlled clinical trial in patients with Huntington’s
disease (HD). The planned progression of SAGE-718 is based on
results from Phase 1 studies evaluating the safety and tolerability
of SAGE-718, including an open-label cohort of patients with
HD.
In the 14-day open-label study of patients with HD, the safety,
tolerability, and pharmacokinetic profile of daily SAGE-718 oral
solution were evaluated in six patients with early HD. In the
study, SAGE-718 was well tolerated, with no serious adverse events
or adverse events leading to treatment discontinuation. In
addition, patients demonstrated improved performance, compared to
baseline, on assessments of executive functioning, with measures
relevant to the core cognitive decline seen in people with HD.
These results are comparable to improvements in measures of
executive function observed in an earlier Phase 1 cohort of
individuals without HD. Additional data from the Phase 1 open-label
cohort study on the safety and tolerability of SAGE-718 in patients
with early HD will be presented at a future congress in 2020.
In addition, the Company is presenting data from three other
non-clinical and Phase 1 studies with SAGE-718 at the 58th Annual
Meeting of the American College of Neuropsychopharmacology (ACNP).
The poster presentations provide supportive evidence for the role
of NMDA receptor dysfunction in Huntington’s Disease-related
cognitive impairment, as well as functional target engagement of
SAGE-718, including positive cognitive effects in healthy
volunteers.
“There is a critical need for better therapeutics to help
patients with cognitive decline, particularly those suffering from
conditions such as Huntington’s disease,” said Mike Quirk, vice
president, pharmacology at Sage. “Discovering and developing
treatments with the potential to quickly and meaningfully improve
the lives of patients is a significant driver of our growing
neuropsychiatry franchise. The SAGE-718 data presented at ACNP,
together with Phase 1 data from patients with Huntington’s Disease,
marks an important achievement for our NMDA platform, and supports
the progression of SAGE-718 to Phase 2.”
Data presentations at ACNP focus on additional studies in HD,
including SAGE-718 data:
Poster [M-147]: Cognitive Deficits in Huntington’s
Disease and Altered 24(S)-hydroxycholesterol
24(S)-hydroxycholesterol (24(S)-HC) is an endogenous,
brain-specific, cholesterol metabolite that acts as a PAM of the
NMDA receptor. Previous work has established that levels of
24(S)-HC are decreased in the plasma and brain in people with
HD.
- In this study, plasma samples from the TRACK-HD study, a
longitudinal observational study of biological and clinical
manifestations of HD, were analyzed.
- Results demonstrated levels of 24(S)-HC declined during the
transition from pre-manifest to manifest HD, and that levels
correlated with performance on tests of executive dysfunction and
emotional processing.
- These data support a role for 24(S)-HC in cognitive changes in
HD and suggest that NMDA hypofunction may contribute to cognitive
impairment in HD.
Poster [M-144]: Using a Multimodal Biomarker Approach to
Identify Functional Target Engagement of the Novel NMDA Positive
Allosteric Modulator SAGE-718
A suite of three clinical studies was designed to evaluate
CNS-target engagement of SAGE-718 by electrophysiology and magnetic
resonance imaging (MRI), using a low-dose ketamine challenge
paradigm in healthy adults in a placebo controlled cross-over
design.
- In these studies, SAGE-718 was generally well tolerated with no
serious adverse events or adverse events leading to treatment
discontinuation.
- A single dose administration of SAGE-718 (3 mg oral solution)
attenuated ketamine-induced changes in functional MRI-derived
alterations of blood oxygenation levels (BOLD), including
attenuation of ketamine-induced increases of BOLD observed in
posterior brain regions and decreases observed in anterior brain
regions (n=13).
- In a single-click, auditory evoked potential paradigm, the
N100-P200 potential waveform was significantly reduced by ketamine
under placebo conditions, but not after administration of SAGE-718
(n=18).
- Results from these studies demonstrate that SAGE-718 had
effects on functional imaging in healthy volunteers. SAGE-718 also
modulated the effects of ketamine on regional and global measures
of resting brain activity. These effects are in line with the
presumed mechanism of action of SAGE-718 as an NMDA PAM, which
supports the hypothesis of functional engagement of the NMDA
receptor.
Poster [M-143]: Cognitive Performance After Repeated
Administration of the NMDA Positive Allosteric Modulator SAGE-718
in Healthy Volunteers
In a double-blind, placebo-controlled study, the effects of
10-day repeated exposure of SAGE-718 on core cognitive battery were
investigated in healthy volunteers. Healthy volunteers (n=40) were
randomized to receive either SAGE-718 1 mg (n=19) plus ketamine or
placebo (n=21) plus ketamine, and computerized testing was used to
measure performance on key cognitive domains, including attention,
working memory, processing speed, executive function, and motor
reaction time.
- Statistically significant improvements were observed compared
to placebo on tests of higher-order working memory (Two-Back Test)
and complex problem solving (Groton Maze Test).
- SAGE-718 was generally well tolerated with no serious adverse
events or adverse events leading to study withdrawal or
discontinuation.
- Improvements in executive performance, as reflected by
significant improvements on the Two-Back and Groton Maze tests,
suggest that SAGE-718 is potentially distinct from other
cognitive-enhancing compounds and supports further investigation of
SAGE-718 for the treatment of conditions characterized by states of
relative NMDA hypofunction, particularly those manifesting with
executive deficits.
About SAGE-718 and NMDA Receptors
SAGE-718 is a novel, oral, first-in-class, oxysterol-based
positive allosteric modulator (PAM) of N-methyl-D-aspartate (NMDA)
receptors. SAGE-718 is the lead compound from Sage's NMDA modulator
platform.
NMDA receptors are glutamate-gated cation channels that play a
critical role in the health and regulation of neurons, and are
involved in learning, memory and neuroplasticity. Positive
modulation of NMDA receptors may have potential benefit in the
treatment of conditions associated with NMDA hypofunction and
disorders associated with a high prevalence of anti-NMDA
antibodies, as well as in disorders associated with reductions in
plasma cerebrosterol, such as Huntington's disease and Alzheimer's
disease.
About Sage Therapeutics
Sage Therapeutics is a biopharmaceutical company committed to
developing novel therapies with the potential to transform the
lives of people with debilitating disorders of the brain. We are
pursuing new pathways with the goal of improving brain health, and
our depression, neurology and neuropsychiatry franchise programs
aim to change how brain disorders are thought about and treated.
Our mission is to make medicines that matter so people can get
better, sooner. For more information, please visit
www.sagerx.com.
Forward-Looking Statements
Various statements in this release concern Sage's future
expectations, plans and prospects, including without limitation:
our views and expectations regarding our development plans for
SAGE-718; our belief in the potential of SAGE-718 in various
indications; the potential profile and benefit of SAGE-718; and the
goals, opportunity and potential for our other product candidates
and business. These statements constitute forward-looking
statements as that term is defined in the Private Securities
Litigation Reform Act of 1995. These forward-looking statements are
neither promises nor guarantees of future performance, and are
subject to a variety of risks and uncertainties, many of which are
beyond our control, which could cause actual results to differ
materially from those contemplated in these forward-looking
statements, including the risks that: we may not be successful in
our development of SAGE-718 or any of our other current or future
product candidates in any indication we are currently pursuing or
may in the future pursue; success in earlier clinical trials or
nonclinical studies may not be repeated or observed in ongoing or
future studies of SAGE-718 or any of our other product candidates;
ongoing and future clinical or nonclinical results may generate
results that are different than we expect or may not support
further development; we may decide that a development pathway for
SAGE-718 or any of our other product candidates in one or more
indications is no longer feasible or advisable or that the unmet
need no longer exists; decisions or actions of the FDA or other
regulatory agencies may affect our plans for development of
SAGE-718, including the initiation, timing, design, size, progress
and cost of clinical trials and our ability to proceed with further
development; we may experience slower than expected initiation or
enrollment in ongoing or future clinical trials; we may encounter
unexpected safety or tolerability issues with SAGE-718 or any of
our other product candidates; the internal and external costs
required for our ongoing and planned research and development
efforts, and to build our organization in connection with such
activities, and the resulting expense increases and use of cash,
may be higher than expected which may cause us to change or curtail
some of our plans; and we may encounter technical and other
unexpected hurdles in the development of SAGE-718 or our other
product candidates; as well as those risks more fully discussed in
the section entitled "Risk Factors" in our most recent quarterly
report filed with the Securities and Exchange Commission (SEC), and
discussions of potential risks, uncertainties, and other important
factors in our subsequent filings with the SEC. In addition, any
forward-looking statements represent our views only as of today,
and should not be relied upon as representing our views as of any
subsequent date. We explicitly disclaim any obligation to update
any forward-looking statements.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191210005515/en/
Investors: Matt Calistri 617-914-2635
matthew.calistri@sagerx.com
Media: Alexis Smith 617-588-3740
Alexis.smith@sagerx.com
Sage Therapeutics (NASDAQ:SAGE)
Historical Stock Chart
From Aug 2024 to Sep 2024
Sage Therapeutics (NASDAQ:SAGE)
Historical Stock Chart
From Sep 2023 to Sep 2024