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 DepressionPostpartum 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 TherapeuticsSage 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 StatementsVarious 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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version on businesswire.com: https://www.businesswire.com/news/home/20180831005484/en/
Sage TherapeuticsInvestor Contact:Paul Cox,
617-299-8377paul.cox@sagerx.comorMedia Contact:Jeff Boyle,
347-247-5089jeff.boyle@sagrerx.com
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