Sage Therapeutics: Positive Results
for Postpartum Depression Drug
December 07, 2017
Sage Therapeutics has reported 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
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
“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
of Top-line Results from the Placebo-Controlled Phase 2
Effect on Depressive Symptoms through end of Treatment
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
Other secondary endpoints
(e.g., MADRS, CGI-I) were similarly highly significant
at Day 15 (p≤0.002).
Effect on Depressive
Symptoms over Time:
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
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
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