MOUNTAIN Study did not meet primary endpoint at
Day 15
Statistical significance on HAM-D scale
achieved at Days 3, 8 and 12; preliminary data from long-term
follow-up suggest maintenance of effect on depressive symptoms
Statistical significance achieved at Days 3, 8,
12 and 15 in patients with measurable drug concentration levels of
SAGE-217
Statistical significance achieved in patients
comparable to those studied in earlier trials with SAGE-217
(HAM-D>24)
SAGE-217 was generally well-tolerated with
safety profile comparable to placebo
Conference call scheduled at 8:30 a.m. EST
Sage Therapeutics (NASDAQ: SAGE), a biopharmaceutical company
developing novel therapies for people with debilitating brain
disorders, today reported topline results from the pivotal Phase 3
MOUNTAIN Study evaluating the effect of SAGE-217 on depressive
symptoms in adults with major depressive disorder (MDD). The
MOUNTAIN Study did not meet its primary endpoint of a statistically
significant reduction from baseline compared to placebo in the
17-item Hamilton Rating Scale for Depression (HAM-D) total score at
Day 15. SAGE-217 30 mg, given once-daily as an oral treatment, was
associated with a mean reduction of 12.6 in HAM-D total score
compared to 11.2 for placebo (p=0.115). Patients in the SAGE-217 30
mg group achieved statistically significant reductions in the HAM-D
total score at Days 3, 8 and 12 (p<0.018 for each timepoint). The SAGE-217
development program includes five other pivotal studies, two of
which have reported positive data, one in MDD and one in postpartum
depression (PPD), and three of which are ongoing.
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Post-hoc analysis revealed that in the MOUNTAIN Study,
approximately 9% of patients in the SAGE-217 30 mg group had no
measurable drug concentration, consistent with non-compliance in
taking SAGE-217. Excluding these patients from the primary analysis
set (SAGE-217 30 mg vs. placebo) resulted in statistical
significance at all timepoints through, and including, Day 15
(p<0.048).
The study enrolled more patients with an overall distribution of
milder severity of symptoms than previous studies of SAGE-217. When
including only patients with a HAM-D>24 (n=124 for SAGE-217 30 mg), a post-hoc
analysis demonstrated statistical significance at all timepoints
through, and including, Day 15 (p<0.032). Analyses utilizing a HAM-D cutoff of
25 or 26 were also statistically significant.
SAGE-217 was generally well-tolerated and showed a similar
safety profile as seen in earlier studies. Overall reports of
adverse events (AEs) during the 14-day treatment period and 28-day
follow-up were similar between SAGE-217 and placebo (30 mg 54.2%,
20 mg 50.0%, placebo 48.9%). The most common AEs (≥5%) in either
SAGE-217 group were headache, dizziness, somnolence, fatigue,
diarrhea, sedation and nausea.
“This study did not meet the primary endpoint. With that, the
data are supportive of the activity of SAGE-217 in MDD given the
statistical significance at the majority of timepoints, and in
relevant populations,” said Jeff Jonas, M.D., chief executive
officer at Sage. “Notwithstanding the finding on the primary
endpoint, the drug displays good activity on most measures. We
understand that drug development is an iterative process. In this
study, we’ve gathered new data on SAGE-217, data we believe support
our hypothesis that SAGE-217 has a unique profile with the
potential for rapid and robust onset with durable effect.”
“These study results reinforce that we have an active drug with
safety data that are consistent with the two earlier pivotal trials
in MDD and PPD,” said Steve Kanes, M.D., Ph.D., chief medical
officer at Sage. “As a designated breakthrough therapy, we are
evaluating the path forward to more fully inform a potentially
expedited pathway to approval, and any amendments we might consider
to the ongoing SAGE-217 pivotal program.”
Summary of topline results from the
MOUNTAIN Study Sage’s Phase 3 MOUNTAIN Study evaluated
the efficacy, safety and pharmacokinetics of SAGE-217 in adult
patients diagnosed with MDD (MADRS total score ≥32 and a HAM-D
total score ≥22).
Effect on depressive symptoms through end of treatment and
follow-up At Day 15, the primary endpoint and end of dosing,
patients randomized to SAGE-217 30 mg demonstrated a reduction in
depressive symptoms of 12.6 in the HAM-D total score compared with
11.2 in patients who received placebo (LS Mean Difference from
placebo -1.4, p=0.115).
Rapid onset of effect for SAGE-217 30 mg (n=166) was noted
beginning at Day 3 and statistical significance from placebo
(n=157) was noted at all visits during the treatment period leading
up to Day 15 (LS Mean Difference from placebo, p-value): Day 3
(-1.6, p=0.016), Day 8 (-2.1, p=0.008) and Day 12 (-2.1,
p=0.018).
Improvements in depressive symptoms were sustained in all
treatment groups through Day 42 of the double-blind portion of the
study. Change from baseline in HAM-D total score at Day 42 for
SAGE-217 30 mg was -11.9 and for placebo was -11.7 (LS Mean
Difference from placebo -0.5, p=0.807). Preliminary data suggest
maintenance of improvement in depressive symptoms in those patients
who have completed long-term follow-up up to 6 months. These data
will continue to be collected in the coming months.
The 20 mg dose of SAGE-217 did not separate from placebo in this
dose-ranging study.
Effect on depressive symptoms by performance factors
Post-hoc analyses were conducted to evaluate the effects of
performance factors on the primary outcome at Day 15.
Change from baseline in HAM-D total score at Day 15, SAGE-217 30
mg vs. placebo:
- Patients with SAGE-217 measurable drug concentrations (n=151)
(excluding 30 mg patients with no measurable drug concentration
consistent with noncompliance): SAGE-217 30 mg (-13.0) vs. placebo
(-11.2); LS Mean Difference -1.8, p=0.048.
- Patients with HAM-D≥24 (n=124): SAGE-217 30 mg (-13.7) vs.
placebo (-11.4); LS Mean Difference -2.3, p=0.032.
- Patients with SAGE-217 measurable drug concentrations and
HAM-D≥24 (n=115): SAGE-217 30 mg (-14.0) vs. placebo (-11.4); LS
Mean Difference -2.6; p=0.017.
Safety and tolerability SAGE-217 was generally well
tolerated in the trial. The overall incidence of patients who
experienced AEs during the 14-day treatment period and 28-day
follow up was 54.2% for SAGE-217 30 mg, 50.0% for SAGE-217 20 mg
and 48.9% for placebo.
- Two patients receiving SAGE-217 30 mg experienced serious
adverse events (SAEs) during treatment: one suicide attempt on Day
5 in a patient with a longstanding history of MDD and a past
suicide attempt, and one report of a bile duct stone after Day 2
requiring removal in a patient with a prior bile duct repair. In
addition, three patients, one in each treatment group, reported
SAEs during follow-up, all occurring at least one week following
cessation of treatment: syncope and associated injuries which
occurred with dehydration and orthostatic hypotension during
exercise in a patient with a history of bradycardia (SAGE-217 30
mg, Day 28), multiple SAEs related to medical complications of
cocaine ingestion (SAGE-217 20 mg, Day 39) and suicidal ideation
(placebo, Day 22).
- The number of subjects having treatment emergent AEs leading to
study drug discontinuation were similar in each treatment group
(SAGE-217 30 mg 2.1%, SAGE-217 20 mg 1.6% and placebo 3.2%).
- The most common AEs (≥5%) in any group (SAGE-217 30 mg,
SAGE-217 20 mg and placebo) during the 14-day treatment period and
the 28-day follow up were:
- Headache (30 mg 6.3%, 20 mg 11.2%, placebo 7.4%)
- Dizziness (30 mg 5.7%, 20 mg 7.4%, placebo 3.7%)
- Somnolence (30 mg 6.8%, 20 mg 5.9%, placebo 4.2%)
- Fatigue (30 mg 6.8%, 20 mg 1.6%, placebo 2.6%)
- Diarrhea (30 mg 6.3%, 20 mg 5.9%, placebo 5.3%)
- Sedation (30 mg 4.7%, 20 mg 5.9%, placebo 3.2%)
- Nausea (30 mg 3.6%, 20 mg 5.3%, placebo 4.7%)
- There were no AEs of loss of consciousness.
- There was no signal for increased suicidal ideation or suicidal
behavior compared to baseline, as measured by Columbia Suicide
Severity Rating Scale (C-SSRS).
Sage plans to present additional results from the MOUNTAIN Study
at an upcoming medical congress.
About the MOUNTAIN Study The MOUNTAIN Study is a
double-blind, placebo-controlled pivotal Phase 3 study evaluating
the efficacy and safety of SAGE-217 in adults with major depressive
disorder (MDD). In the study, 581 patients were randomized to
receive SAGE-217, 20 mg or 30 mg, or placebo, once-nightly for
two-weeks. The primary endpoint of the study is the change from
baseline in the 17-item Hamilton Rating Scale for Depression
(HAM-D) total score at Day 15. Secondary endpoints include the
change from baseline in the Montgomery-Åsberg Depression Rating
Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) total
score, among others.
About Major Depressive Disorder Major depressive disorder
(MDD), commonly referred to as depression, is a brain health
disorder that affects an estimated 17 million adults in the U.S.
each year. It is one of the largest contributors to disability in
the U.S. and worldwide and is characterized by symptoms of
depressed mood and/or loss of interest in pleasurable activities.
MDD causes significant impairment in daily life and can limit a
person’s ability to fulfill work, school, family, or social
responsibilities; enjoy leisure activities; or maintain health and
hygiene. While antidepressants are widely used to treat MDD,
large-scale studies have demonstrated that there is an unmet need
in the treatment of MDD as well as the need for new therapeutic
options.
About SAGE-217 SAGE-217 is an investigational, oral,
novel medicine in development for depression. SAGE-217 is an
investigational oral neuroactive steroid (NAS) GABAA receptor
positive allosteric modulator (PAM). The GABA system is the major
inhibitory signaling pathway of the brain and central nervous
system (CNS), and contributes significantly to regulating CNS
function.
The clinical program evaluating SAGE-217 in depression is
progressing. To date, two positive pivotal studies have been
completed, one in MDD (MDD-201) and one in postpartum depression
(ROBIN Study). Ongoing studies include the REDWOOD, SHORELINE and
RAINFOREST studies.
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
the potential of SAGE-217 in the treatment of depression; our views
as to the potential profile and benefit of SAGE-217; our plans and
expectations related to ongoing development of SAGE-217, the
potential pathway for approval and next steps; and our plans,
goals, opportunity and potential for our programs 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-217
in depression or of 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; ongoing and future clinical or nonclinical results
may generate results that are different than we expect or may not
support further development or be sufficient to gain regulatory
approval of SAGE-217 or any of our other product candidates; the
FDA may decide that the development program for SAGE-217, or any of
our product candidates, is not sufficient for a new drug
application filing or approval and may require completion of
additional clinical trials or nonclinical studies; we may decide
that a development pathway for one of our 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 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;
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-217 or any of 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.
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Investor Contact: Matt Calistri, 617-914-2635
matthew.calistri@sagerx.com Media Contact: Jeff Boyle,
347-247-5089 jeff.boyle@sagerx.com
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