– SAGE-217 met primary endpoint and provided
rapid, profound and durable effects through 2-week treatment period
and additional 4-week follow-up –
– Well-tolerated and demonstrated highly
statistically significant mean reduction in the HAM-D score
compared to placebo at 15 days (p<0.0001) beginning after one
dose and maintained through Week 4 with numerical superiority
though Week 6 –
– All secondary endpoints were consistent with
primary endpoints at Day 15, including remission in 64% of SAGE-217
patients versus 23% of placebo patients (p=0.0005) –
– Data support further development of SAGE-217
for MDD and related disorders –
– Conference call scheduled today at 8:00 A.M.
ET –
Sage Therapeutics (NASDAQ: SAGE), a clinical-stage
biopharmaceutical company developing novel medicines to treat
life-altering central nervous system (CNS) disorders, today
announced positive top-line results from the Phase 2, double-blind,
placebo-controlled clinical trial of SAGE-217 in the treatment of
89 adult patients with moderate to severe major depressive disorder
(MDD). In the trial, treatment for 14 days with SAGE-217 was
associated with a statistically significant mean reduction in the
Hamilton Rating Scale for Depression (HAM-D) 17-Item total score
from baseline to Day 15 (the time of the primary endpoint) of 17.6
points for SAGE-217, compared to 10.7 for placebo (p<0.0001).
Statistically significant improvements were observed in the HAM-D
compared to placebo by the morning following the first dose through
Week 4 and the effects of SAGE-217 remained numerically greater
than placebo through the end of follow-up at Week 6. At Day 15, 64
percent of patients who received SAGE-217 achieved remission,
defined as a score of 7 or less on the HAM-D scale, compared with
23 percent of patients who received placebo (p=0.0005). Other
secondary endpoints were all similarly highly significant at Day 15
(p≤0.002).
SAGE-217 was generally well-tolerated with no serious or severe
adverse events; the most common adverse events (AEs) in the
SAGE-217 group were headache, dizziness, nausea, and somnolence. A
low rate of discontinuations due to AEs was reported; overall
reports of AEs were similar between drug (53%) and placebo (46%),
with a safety profile consistent with that seen in earlier trials.
SAGE-217 was granted Fast Track Designation by the U.S. Food and
Drug Administration (FDA) in May 2017.
“These very encouraging data suggest the potential of SAGE-217
in the treatment of MDD as well as other mood-related disorders
that we may pursue,” said Jeff Jonas M.D., chief executive officer
of Sage Therapeutics. “There has been little innovation in the
discovery and development of treatments for depression in the last
two decades. Coupled with our recent positive Phase 3 data read-out
evaluating brexanolone for the treatment of postpartum depression,
the findings in this study suggest our pipeline of proprietary
GABAA modulators may impact novel and fundamental brain mechanisms,
offering potential development opportunities in a variety of
indications. The positive activity and safety findings of SAGE-217
in MDD support advancing the program into later stage clinical
development and we will work with the FDA to determine next steps
in the further development of SAGE-217.”
The GABA system is the major inhibitory signaling pathway of the
central nervous system (CNS), and contributes significantly to
regulating CNS function. SAGE-217 is a novel, highly potent and
selective, next generation GABAA receptor positive allosteric
modulator that is being developed as a once-daily, oral therapy for
the treatment of various CNS disorders. SAGE-217 was discovered by
Sage, and the Company maintains worldwide rights to the
compound.
“There are currently significant gaps in the disease management
of depression and our development goal at Sage is to change
patients’ expectations by transforming the treatment landscape for
MDD,” said Steve Kanes, M.D., Ph.D., chief medical officer of Sage
Therapeutics. “If successfully developed, SAGE-217 has the
potential to offer the first truly new mechanism of action in the
pharmacologic treatment of depression in more than 20 years. If the
results from this trial are replicated in Phase 3 trials, SAGE-217
may meet the needs of patients with MDD for a once-daily oral
treatment that potentially provides a rapid, well-tolerated and
durable response with a high rate of remission.”
Summary of Top-line Results from the
Placebo-Controlled Phase 2 TrialEffect on Depressive
Symptoms through end of Treatment (Day 15):
- Treatment with SAGE-217 was associated
with a statistically significant mean reduction from baseline in
the Hamilton Rating Scale for Depression (HAM-D) total score at Day
15 of 17.6 points compared with a 10.7 point mean reduction
associated with placebo (p<0.0001).
- The majority of patients (64%) who
received SAGE-217 achieved remission at Day 15 as determined by a
HAM-D total score less than or equal to 7 (compared with 23% of
patients who received placebo, p=0.0005).
- Other secondary endpoints (e.g., MADRS,
CGI-I) were similarly highly significant at Day 15 (p≤0.002).
Effect on Depressive Symptoms over Time:
- Statistically significant mean
reductions from baseline in the Hamilton Rating Scale for
Depression (HAM-D) total score were observed following the first
dose (Day 2) and maintained through Week 4, two weeks after end of
treatment (p<0.0318).
- At Week 4, the mean reduction from
baseline in HAM-D total score was 15.6 for the SAGE-217 group and
11.9 for the placebo group (p=0.0243).
- At Week 6, the mean reduction in HAM-D
total score for the SAGE-217 group was 15.0 and numerically, but
not statistically improved compared to the placebo group reduction
of 13.0.
- Rates of remission at Week 4 and Week 6
for patients treated with SAGE-217 were 52 percent and 45 percent
compared to 28 percent and 33 percent for placebo, with statistical
significance maintained at Week 4 (p=0.0221) but not Week 6.
Safety and Tolerability:
- SAGE-217 was generally well tolerated
in the trial. The overall incidence of patients who experienced
adverse events was 53 percent for the SAGE-217 treatment group and
46 percent for the placebo group.
- There were no deaths, serious or severe
adverse events.
- Rates of discontinuation from dosing of
study drug due to adverse events were low; two patients (4.4%)
treated with SAGE-217 and none treated with placebo.
- The most common adverse events in the
SAGE-217 group were headache, dizziness, nausea and
somnolence.
- There was no signal for increased risk
for patients treated with SAGE-217 as measured by structured
assessments of suicidality and sedation.
Conference Call InformationSage will host a conference
call and webcast today at 8:00 A.M. ET to discuss the top-line
results from the Phase 2 SAGE-217 trial in MDD. The live webcast
can be accessed on the investor page of Sage’s website at
investor.sagerx.com. The conference call can be accessed by dialing
866-450-8683 (toll-free domestic) or 281-542-4847 (international)
and using the conference ID 2675527. A replay of the webcast will
be available on Sage’s website approximately two hours after the
completion of the event and will be archived for up to 30 days.
About the Placebo-controlled Phase 2 trial of SAGE-217 in
MDD:In the randomized, double-blind, parallel-group,
placebo-controlled trial, 89 eligible patients (with a minimum
total score of 22 on the Hamilton Rating Scale for Depression) were
stratified based on use of antidepressant treatment (current/stable
or not treated/withdrawn ≥30 days) and randomized in a 1:1 ratio to
receive SAGE-217 Capsules (30mg) (n=45) or matching placebo (n=44).
All doses of study drug were administered at night with food. The
study consisted of a 14-day treatment period, and a 4-week
follow-up period. The mean HAM-D total scores at baseline were 25.2
for the SAGE-217 group and 25.7 for the placebo group (overall
range 22-33), representing patients with moderate to severe MDD.
Approximately 90 percent of patients in each group completed the
study.
About Major Depressive DisorderMajor depressive disorder
(MDD) is a common but serious mood disorder in which patients
exhibit depressive symptoms, such as a depressed mood or a loss of
interest or pleasure in daily activities consistently for at least
a two-week period, and demonstrate impaired social, occupational,
educational or other important functioning. It is estimated that
approximately 16 million people in the U.S. suffer from MDD each
year. While antidepressants are widely used for treatment, large
scale studies have demonstrated the need for additional
therapies.
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 in clinical research 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 SAGE-217SAGE-217 is a next generation positive
allosteric modulator that has been optimized for selectivity to
synaptic and extrasynaptic GABA receptors and a pharmacokinetic
profile intended for daily oral dosing. The GABA system is the
major inhibitory signaling pathway of the brain and CNS, and
contributes significantly to regulating CNS function. SAGE-217 is
currently being developed for MDD and certain other mood and
movement disorders.
About Sage TherapeuticsSage Therapeutics is a
clinical-stage biopharmaceutical company committed to developing
novel medicines to transform the lives of patients with
life-altering central nervous system (CNS) disorders. Sage has a
portfolio of novel product candidates targeting critical CNS
receptor systems, GABA and NMDA. Sage's lead program, a proprietary
IV formulation of brexanolone (SAGE-547), is in Phase 3 clinical
development for postpartum depression. Sage is developing its next
generation modulators, including SAGE-217 and SAGE-718, in various
CNS disorders. 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 SAGE-217 in the treatment of MDD and related
disorders; our statements regarding plans for further development
of SAGE-217 and related regulatory activities and the potential for
successful development; our view of the potential of the GABA
mechanism and our product candidates, including SAGE-217, in the
treatment of CNS diseases and disorders; our views as to the unmet
need for additional treatment options in MDD and the potential of
SAGE-217 to meet the unmet need, and our estimates as to the number
of patients with MDD. 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 able to successfully demonstrate the
efficacy and safety of SAGE-217 or any of our other product
candidates at each stage of development; success in early stage
clinical trials may not be repeated or observed in ongoing or
future studies of SAGE-217 or any of our other product candidates;
ongoing and future clinical results may not support further
development or be sufficient to gain regulatory approval to market
SAGE-217 or any of our other 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; 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 encounter unexpected
safety or tolerability issues with SAGE-217 or any of our other
product candidates in ongoing or future development; the actual
size of the MDD patient population may be significantly lower than
our estimates and, even if SAGE-217 is successfully developed and
approved for MDD, it may only be approved or used to treat a subset
of the MDD population; and we may encounter technical and other
unexpected hurdles in the development and manufacture 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 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: http://www.businesswire.com/news/home/20171207005149/en/
Investor Contact:Sage TherapeuticsPaul Cox,
617-299-8377paul.cox@sagerx.comorMedia Contact:Suda
Communications LLCMaureen L. Suda,
585-355-1134maureen.suda@sagerx.com
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