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Sage Therapeutics Announces The Lancet Publishes Integrated Data from Pivotal Trials for Brexanolone Injection in Postpartum Depression

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Results from pivotal trials consistently showed treatment with
brexanolone injection provided significant and rapid reduction in
depressive symptoms within days of initiating therapy

Treatment response was durable over the follow-up period, across
three placebo-controlled trials

ZULRESSO™ (brexanolone injection) New Drug Application currently
under review with U.S. FDA and, if approved, would be the first medicine
indicated for the treatment of postpartum depression

Sage Therapeutics (NASDAQ:SAGE), a clinical-stage biopharmaceutical
company developing novel medicines to treat life-altering central
nervous system (CNS) disorders, today announced The
Lancet
has published an integrated analysis across three,
double-blind, randomized, placebo-controlled studies of brexanolone
injection in women with postpartum depression (PPD). This new analysis,
published for the first time, demonstrated significant and clinically
meaningful reductions in HAM-D total score, a common measure of
depression severity, following treatment with brexanolone 90 µg/kg/h at
the primary timepoint of 60 hours compared with placebo. Statistically
significant improvement in the HAM-D total score was first observed
within 24 hours of initiating treatment and treatment response was
durable through the 30-day follow-up. The most common adverse events
during treatment across all studies were headache, dizziness and
somnolence. The FDA has conditionally accepted the proprietary name
ZULRESSO™ for Sage's intravenous formulation of brexanolone.

"Postpartum depression is one of the most common complications of
childbirth and it impacts the mother, her children, and the entire
family," said Samantha Meltzer-Brody, M.D., M.P.H., Ray M Hayworth and
Family Distinguished Professor of Mood and Anxiety Disorders and
Director of the UNC Perinatal Psychiatry Program of the UNC Center for
Women's Mood Disorders and primary investigator of the study. "I've been
treating women with PPD for close to 25 years and the ability to rapidly
treat the devastating symptoms of PPD would be a game changer for these
women and their families. PPD symptoms vary for each mother, but may
include sadness, anxiety, irritability, withdrawing from friends or
family, having trouble bonding with her baby and thinking about harming
herself and more rarely, her baby. Currently, there are not any
pharmacologic treatments specifically approved for PPD. These new
brexanolone data represent a significant shift in our understanding of
how PPD may be treated in the future."

It is estimated that PPD affects approximately 10-20 percent of women
giving birth globally. In the United States, estimates of new mothers
identified with PDD each year vary by state from 8-20 percent, with an
overall average of 11.5 percent.

"The stigma attached to maternal mental health often prevents mothers
from seeking help and these data represent an exciting step forward in
developing a treatment for people whose disorders have been ignored,"
said Steve Kanes, M.D., Ph.D., chief medical officer of Sage and lead
author of the paper. "These data show a profound, rapid and durable
reduction in PPD symptoms was achieved during the study period among the
majority of participants receiving brexanolone. We believe these results
validate our clinical approach to drug development and our efforts to
bring treatments to areas of significant unmet need. ZULRESSO is
currently under review by the FDA as a treatment for postpartum
depression and, if approved, has the potential to significantly improve
the treatment options for PPD, which is great news for mothers and
families."

The paper, titled "Brexanolone
Injection in Post-Partum Depression: Two Multicentre, Double-blind,
Randomised, Placebo-controlled Phase 3 Trials
," includes integrated
results from three pivotal, placebo-controlled trials of brexanolone in
women with a range of PPD severities.

An analysis of the integrated comparative efficacy of brexanolone
injection 90 µg/kg/hr [BRX90] versus placebo groups across two Phase 3
studies (studies 1 & 2) and one Phase 2 study completed in 2017 was
conducted; as a unique dose group, brexanolone injection 60 µg/kg/hr
[BRX60] in study 2 was not included in the integrated efficacy analysis
but was included in integrated analyses of safety.

Mean pre-dose HAM-D total scores for the integrated BRX90 arms and
placebo arms were 25.5 and 25.7, respectively. At the 60-hour primary
timepoint, there were significantly larger mean reductions from baseline
in HAM-D total scores with BRX90 relative to placebo (-17.0 vs. -12.8;
p<0.0001). These treatment differences at Hour 60 were maintained at Day
30 (BRX90, -16.9; placebo, -14.3; p=0.0213). Brexanolone injection
showed similar results in subjects with and without a concomitant
antidepressant use, with both subgroups demonstrating significant
differences in change from baseline HAM-D total score versus placebo at
Hour 60 (no antidepressant: BRX90, -16.9; placebo, -12.6; p<0.0001;
concomitant antidepressant: BRX90, -17.4; placebo, -13.0; p=0.0282).
Additionally, brexanolone injection had higher rates of remission
(defined as HAM-D total score ≤7; BRX90, 50.0%; placebo, 26.4%;
p<0.0001) and response (defined as ≥50% reduction in HAM-D total score;
BRX90, 74.5%; placebo, 5.7%; p=0.0003) than placebo at Hour 60.

Across all brexanolone injection subjects, including subjects who
received BRX60, there were two (1%) brexanolone subjects with at least
one serious adverse event (vs. no placebo subjects), and there were
three (2%) brexanolone subjects with at least one severe adverse event
compared with two (2%) placebo subjects. There were no deaths. There was
a similar percentage of subjects with at least one adverse event between
treatments (50% on brexanolone injection vs. 51% on placebo). The most
common (≥10% of subjects) AEs during brexanolone injection
administration were headache, dizziness, and somnolence.

About Postpartum Depression
Postpartum depression (PPD) is a
distinct and readily identified major depressive disorder that is the
most common medical complication of childbirth, affecting a subset of
women typically commencing in the third trimester of pregnancy or within
four weeks after giving birth. PPD may have devastating consequences for
a woman and for her family, which may include significant functional
impairment, depressed mood and/or loss of interest in her newborn, and
associated symptoms of depression such as loss of appetite, difficulty
sleeping, motor challenges, lack of concentration, loss of energy and
poor self-esteem. Suicide is the leading cause of maternal death
following childbirth. In the U.S., estimates of new mothers identified
with PPD each year vary by state from 8 to 20 percent, with an overall
average of 11.5 percent. More than half of these cases may go
undiagnosed without proper screening. There are no FDA approved
therapies for PPD and there is a high unmet medical need for improved
pharmacological therapy in PPD.

About the Hamilton Rating Scale for Depression (HAM-D)
HAM-D
is a validated rating scale used to provide an assessment of depression,
and as a guide to evaluate recovery. This scale is an accepted
regulatory endpoint for depression. The scale is used to rate the
severity of a patient's depression by probing mood, feelings of guilt,
suicide ideation, insomnia, agitation, anxiety, weight loss, and somatic
symptoms.

About ZULRESSO™ (brexanolone injection)
Brexanolone is an
allosteric modulator of both synaptic and extrasynaptic GABAA
receptors. Allosteric modulation of neurotransmitter receptor activity
results in varying degrees of desired activity rather than complete
activation or inhibition of the receptor. ZULRESSO (brexanolone
injection) has completed Phase 3 clinical development for postpartum
depression and a New Drug Application is currently under review with the
U.S. Food and Drug Administration. ZULRESSO for the treatment of PPD has
been granted Breakthrough Therapy Designation by the FDA and PRIority
MEdicines (PRIME) designation from the European Medicines Agency (EMA).

About Sage Therapeutics
Sage Therapeutics is a
clinical-stage biopharmaceutical company committed to developing novel
medicines to transform the lives of patients with life-altering CNS
disorders. Sage's lead product candidate, ZULRESSO (brexanolone
injection), has completed Phase 3 clinical development for postpartum
depression and a New Drug Application is currently under review with the
U.S. Food and Drug Administration. Sage is developing a portfolio of
novel product candidates targeting critical CNS receptor systems,
including SAGE-217, which is in Phase 3 development in major depressive
disorder and postpartum depression. 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 expectations regarding the potential
for approval of our NDA for brexanolone IV in the treatment of PPD; our
views as to the potential of brexanolone IV to represent a paradigm
shift in the treatment of PDD, and to improve treatment options; our
estimates of the prevalence of PPD; and our views as to the opportunity
represented by Sage's portfolio and business. 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: the FDA may decide not to approve our NDA for
brexanolone IV in PPD; the clinical and non-clinical data we have
generated with our proprietary formulation of brexanolone to date may be
determined by the FDA and other regulatory authorities, despite prior
advice, to be insufficient to gain regulatory approval to launch and
commercialize our product in PPD and regulatory authorities may
determine that additional trials or data are necessary in order to
obtain approval; regulatory authorities may find fault with the data
generated at particular clinical site or sites or with the activities of
our trial monitor or may disagree with our analyses of the results of
our trials or identify issues with our manufacturing or quality systems,
and any such findings or issues could require additional data or
analyses or changes to our systems that could delay or prevent us from
gaining approval of brexanolone IV; even if brexanolone IV is approved
in PPD, regulatory authorities may impose significant restrictions or
conditions on use or on administration, including on sites of care; the
number of women with PPD, and the actual market for brexanolone IV, may
be smaller than our current estimates; we may encounter unexpected
safety or tolerability issues with respect to brexanolone IV or any of
our other product candidates; we may not be successful in our
development of any of our product candidates in any indication we are
currently pursuing or may in the future pursue; success in early stage
clinical trials may not be repeated or observed in ongoing or future
studies of our product candidates; ongoing and future clinical results
may not support further development or be sufficient to gain regulatory
approval of our product candidates; 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;
and we may encounter new data or technical and other unexpected hurdles
in the development, manufacture and potential future commercialization
of our product candidates; as well as those risks more fully discussed
in the section entitled "Risk Factors" in our most recent Quarterly
Report on Form 10-Q, and discussions of potential risks, uncertainties,
and other important factors in our subsequent filings with the
Securities and Exchange Commission. 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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