At the Day 3 primary endpoint, zuranolone 50 mg
co-initiated with a standard of care antidepressant showed a
statistically significant reduction in depressive symptoms
Key secondary endpoint demonstrates zuranolone
co-initiated with an antidepressant was statistically significant
in reducing depressive symptoms compared to an antidepressant
co-initiated with placebo over the 2-week treatment period
Zuranolone 50 mg co-initiated with a standard
of care antidepressant was generally well-tolerated with most TEAEs
reported as mild or moderate and no new safety signals
identified
Sage Therapeutics to host conference call today
at 8:00 a.m. ET
Sage Therapeutics, Inc. (Nasdaq: SAGE), and Biogen Inc. (Nasdaq:
BIIB) today announced the CORAL Study in people with major
depressive disorder (MDD) met the trial objectives, demonstrating a
rapid and statistically significant reduction in depressive
symptoms at Day 3 and over the 2-week treatment period, achieving
the primary and key secondary endpoints. This significance was
demonstrated at the first measured time point, Day 3, with
zuranolone 50 mg co-initiated with an open-label standard of care
antidepressant (ADT) as assessed by change from baseline in the
17-item Hamilton Rating Scale for Depression (HAMD-17). The CORAL
Study also met its key secondary endpoint, with zuranolone
co-initiated with a standard of care ADT demonstrating a
statistically significant improvement in depressive symptoms
compared to ADT co-initiated with placebo, over the 2-week
treatment period. Zuranolone was generally well-tolerated, and no
new safety signals attributable to zuranolone were identified. In
meeting its pre-defined objectives, the CORAL Study supports the
potential of zuranolone, when co-initiated with standard of care,
to accelerate the benefit of depression treatment compared to
treatment with ADTs alone.
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The CORAL Study was an active comparator trial comparing the
combination of zuranolone 50 mg co-initiated with an active
standard of care ADT to standard of care ADT co-initiated with
placebo in people with MDD blinded to receipt of zuranolone or
placebo. The trial demonstrated a mean change from baseline in
HAMD-17 total score of -8.9 ± 0.39 (n=210) at Day 3 for people in
the zuranolone co-initiated with ADT arm compared with -7.0 ± 0.38
(n=215) mean change from baseline for people in the ADT
co-initiated with placebo arm. The key secondary endpoint measured
the treatment effect over the 2-week treatment period at all
scheduled visits (measured using equal weighted means for Days 3,
8, 12 and 15 of the study). The mean change over the treatment
period for people who received zuranolone co-initiated with an ADT
was -11.7 ±0.40 (n=210) compared with -10.1 ±0.39 (n=215) for
people who received ADT co-initiated with placebo. Other secondary
endpoints demonstrated a statistically significant reduction in
HAMD-17 score in the zuranolone co-initiated with ADT arm compared
to the ADT arm at Days 8 and 12, while Day 15 demonstrated
numerical superiority and Day 42 showed equivalence.
Based on consistent findings suggesting a benefit of zuranolone
in people with MDD with elevated anxiety across the LANDSCAPE
program, the CORAL Study prospectively examined this population. In
this CORAL Study subgroup (n=218 of 425 people (51.3%) with HAM-A
total score ≥20 at baseline) zuranolone co-initiated with an ADT
was nominally statistically significant to ADT with placebo in
reducing depressive symptoms as measured by the primary endpoint
(-9.3 compared to -6.0; HAMD-17 total score change from baseline)
and key secondary endpoint (-11.7 compared to -9.4; HAMD-17 total
score change from baseline) demonstrating the potential to address
the unmet need for this population, which has been historically
less responsive to chronically administered ADTs.
“We believe the CORAL Study is clinically meaningful and with
the addition of this data the LANDSCAPE program now demonstrates
zuranolone has three potential real world uses for the treatment of
MDD. The LANDSCAPE data support zuranolone as a monotherapy, and
since many people in the previously completed studies were already
on maintenance ADTs, we believe our data also support zuranolone as
additive therapy. The CORAL Study further supports the use of
zuranolone to accelerate the benefit of conventional ADTs in
treating MDD with a well-tolerated safety profile,” said Barry
Greene, Chief Executive Officer at Sage. “Including the CORAL
Study, zuranolone now has six positive clinical studies, and we
remain on track to start the rolling submission for a New Drug
Application in MDD early this year with completion targeted for the
second half of 2022.”
“These positive results from the CORAL Study indicate that
zuranolone co-initiated with standard of care may offer more rapid
relief from depressive symptoms than current standard of care taken
alone,” said Priya Singhal, M.D., M.P.H., Head of Global Safety and
Regulatory Sciences and Interim Head of R&D at Biogen. “Based
on the collective results observed across the LANDSCAPE clinical
development program, we believe that zuranolone has the potential
to offer a new clinically meaningful treatment option for people
with major depressive disorder.”
In the CORAL Study, zuranolone 50 mg co-initiated with a
standard of care ADT was generally well-tolerated with no new
safety signals identified. The majority of people in the study
experienced treatment emergent adverse events (TEAEs) that were
mild or moderate in severity, consistent with previous data in the
LANDSCAPE program. The adverse events occurring 10% or higher in
the zuranolone plus ADT arm were somnolence (18.4%), dizziness
(13.2%) and headache (11.8%). In the ADT plus placebo arm the AEs
occurring 10% or greater were headache (14.7%) and nausea (23.4%).
The CORAL Study safety data support the known safety profile of
zuranolone based on clinical trials to date.
“The CORAL Study results were particularly interesting because
the data demonstrated that zuranolone worked within days to provide
rapid reduction in depressive symptoms as compared to current ADTs,
which in clinical practice can take weeks or months to work,” said
Sagar Parikh, MD, Professor of Depression and Clinical
Neuroscience, and Psychiatry Sciences, University of Michigan. “In
my experience, people with MDD deserve to feel better as soon as
possible with a treatment with tolerable side effects. These data
suggest that zuranolone has the potential to offer this option and
to provide physicians the opportunity to think differently about
treating MDD.”
The Phase 3 CORAL Study builds on the foundational data
assembled within the LANDSCAPE clinical program to date. Data from
this program has been presented at numerous medical and scientific
conferences, and the companies plan to present additional data from
the CORAL Study in future scientific forums.
CORAL Study Summary Results
The CORAL Study was a Phase 3, randomized, double-blind,
placebo-controlled trial, which enrolled 440 people with MDD (n=220
per treatment arm). People in the study received zuranolone 50 mg
co-initiated with an open-label standard of care ADT or open-label
standard of care ADT co-initiated with placebo once nightly for 14
days. Results for the primary and key secondary efficacy endpoints
during the treatment period are outlined in the following table and
all favor zuranolone.
- The mean (SD) baseline HAMD-17 score at entry into the study
was 26.8 (2.5) in the zuranolone co-initiated with ADT arm and 26.6
(2.6) in the ADT co-initiated with placebo arm.
- 180 (84.9%) people in the study who received zuranolone
co-initiated with ADT, and 177 (81.2%) people who received ADT
co-initiated with placebo, completed the study.
Zuranolone 50 mg co- initiated
with an ADT
ADT co-initiated with
placebo
LS Mean HAMD-17 Total Score
CFB (n= 210)
LS Mean HAMD-17 Total Score
CFB (n=215)
p value
Day 3 Primary Endpoint
-8.9
-7.0
0.0004
Key Secondary Endpoint
LS Mean Change in HAMD-17 total score
using equal weights for Days 3, 8, 12, and 15 (over the blinded
treatment period)
-11.7
-10.1
0.0054
ADT = antidepressant; CFB = change from
baseline; HAMD-17 = 17-item Hamilton Depression Rating Scale; LS
Mean = Least Squares Mean
Mean CFB in HAMD-17
Total Score at Each Time Point in the Blinded Treatment Period
(Applied to Calculate the Key Secondary Endpoint)
Zuranolone 50 mg co-initiated
with an ADT
ADT co-initiated with
placebo
LS Mean HAMD-17 Total Score
CFB
LS Mean HAMD-17 Total Score
CFB
p value
Day 3 Primary Endpoint
-8.9
-7.0
0.0004
Day 8
-11.3
-9.2
0.0012
Day 12
-12.8
-11.4
0.0381
Day 15
-13.7
-12.9
0.2477
ADT = antidepressant; CFB = change from
baseline; HAMD-17 = 17-item Hamilton Depression Rating Scale; LS
Mean = Least Squares Mean
Safety and tolerability of zuranolone 50 mg co-initiated with
an ADT:
- Over the study period, the AEs 10% or higher in either
treatment arm (zuranolone with an ADT vs. ADT with placebo) were:
somnolence (18.4% vs 8.3%), dizziness (13.2% vs 7.3%), headache
(11.8% vs 14.7%), and nausea (9.0% vs 23.4%).
- The percentage of people reporting TEAEs leading to
discontinuation of study drug were 6.6% in the zuranolone
co-initiated with an ADT arm, and 3.7% in the ADT co-initiated
placebo arm, respectively. Similarly, the percentage of people
reporting TEAEs leading to discontinuation of ADT were 7.5% in the
zuranolone co-initiated with an ADT arm, and 5.5% in the ADT
co-initiated placebo arm, respectively.
- No evidence of increased suicidal ideation/behavior was
identified with zuranolone when co-initiated with an ADT compared
with ADT co-initiated with placebo as measured by the
Columbia-Suicide Severity Rating Scale (C-SSRS), and systematic
evaluations revealed no evidence of withdrawal symptoms in either
study arm.
Conference Call Information Sage will host a conference
call and webcast on February 16 at 8:00 a.m. ET to review the
totality of the CORAL Study. The live webcast can be accessed on
the investor page of Sage's website at investor.sagerx.com. 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 CORAL Study The
CORAL Study (217-MDD-305) was a Phase 3, randomized, double-blind,
placebo-controlled trial assessing the efficacy and safety of
zuranolone 50 mg co-initiated with an open-label standard of care
antidepressant (ADT) compared to a standard of care ADT
co-initiated with placebo in adults with MDD. In the study, 440
people were enrolled. People in the study were randomized to
receive zuranolone 50 mg with a standard of care ADT or a standard
of care ADT co-initiated with placebo once nightly for two weeks.
People in the study were then followed for four weeks during which
they continued their ADT. The study included five ADTs across
different SSRI and SNRIs (sertraline, escitalopram, citalopram,
duloxetine, desvenlafaxine) that represent the most commonly used
ADTs. The choice of ADT was made by the clinician. The primary
endpoint was the change in baseline 17-item Hamilton Rating Scale
for Depression (HAMD-17) total score at Day 3.
About Major Depressive Disorder (MDD) Major depressive
disorder (MDD) is a common but serious mood disorder in which
people experience depressive symptoms that impair their social,
occupational, educational, or other important functioning, such as
a depressed mood or loss of interest or pleasure in daily
activities, consistently for at least a two-week period. It is
estimated that more than 19 million adults in the U.S. and more
than 260 million people worldwide suffer from depression. While
antidepressants are widely used to treat MDD, large-scale studies
have demonstrated the need for additional therapies with a
differentiated profile.
About Zuranolone Zuranolone (SAGE-217/BIIB125) is a
once-daily, two-week, investigational drug in development for the
treatment of major depressive disorder (MDD) and postpartum
depression (PPD). Zuranolone is an investigational oral neuroactive
steroid (NAS) GABA-A receptor positive allosteric modulator (PAM).
The GABA system is the major inhibitory signaling pathway of the
brain and central nervous system and contributes to regulating
brain function.
Zuranolone is being evaluated in the LANDSCAPE and NEST clinical
trial programs. The two development programs include multiple
studies examining use of zuranolone in several thousand people with
a variety of dosing, clinical endpoints, and treatment paradigms.
The LANDSCAPE program includes five studies of zuranolone in people
with MDD (MDD-201B, MOUNTAIN, SHORELINE, WATERFALL, and CORAL
Studies). The NEST program includes two placebo-controlled studies
of zuranolone in people with PPD (ROBIN and SKYLARK Studies).
Additionally, Shionogi recently completed a Phase 2 study of
zuranolone in Japan in people with MDD.
About Sage Therapeutics Sage Therapeutics is a
biopharmaceutical company fearlessly leading the way to create a
world with better brain health. Our mission is to pioneer solutions
to deliver life-changing brain health medicines, so every person
can thrive. For more information, please visit. www.sagerx.com.
About Biogen As pioneers in neuroscience, Biogen
discovers, develops, and delivers worldwide innovative therapies
for people living with serious neurological diseases as well as
related therapeutic adjacencies. One of the world’s first global
biotechnology companies, Biogen was founded in 1978 by Charles
Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize
winners Walter Gilbert and Phillip Sharp. Today, Biogen has a
leading portfolio of medicines to treat multiple sclerosis, has
introduced the first approved treatment for spinal muscular
atrophy, and is providing the first and only approved treatment to
address a defining pathology of Alzheimer’s disease. Biogen is also
commercializing biosimilars and focusing on advancing the
industry’s most diversified pipeline in neuroscience that will
transform the standard of care for patients in several areas of
high unmet need.
In 2020, Biogen launched a bold 20-year, $250 million initiative
to address the deeply interrelated issues of climate, health, and
equity. Healthy Climate, Healthy Lives™ aims to eliminate fossil
fuels across the company’s operations, build collaborations with
renowned institutions to advance the science to improve human
health outcomes, and support underserved communities.
We routinely post information that may be important to investors
on our website at www.biogen.com. Follow us on social media -
Twitter, LinkedIn, Facebook, YouTube.
Forward-Looking Statements
Sage Therapeutics Safe Harbor Various statements in this
release concern Sage's future expectations, plans and prospects,
including without limitation our statements regarding: the
potential for zuranolone, if approved; our belief in the potential
profile, benefit and impact of zuranolone in the treatment of MDD,
if approved, and the unmet need for new treatment options; our
estimates as to the number of people with MDD; our future plans and
expected activities; and the mission and goals for our 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 experience delays or unexpected hurdles in our
efforts to file a new drug application (“NDA”) and seek approval of
zuranolone in the treatment of MDD or PPD; even if we are
successful in our efforts to file an NDA for zuranolone, the FDA
may find that the data included in the NDA are not sufficient for
approval and may not approve the NDA; the FDA may decide that the
design, conduct or results of our completed and ongoing clinical
trials for zuranolone, even if positive, are not sufficient for
approval in MDD or PPD and may require additional trials or data
which may significantly delay and put at risk our efforts to obtain
approval and may not be successful; other decisions or actions of
the FDA or other regulatory agencies may affect our efforts with
respect to zuranolone and our plans, progress or results; we may
experience negative results in ongoing or future studies of
zuranolone that negatively affect our ability to obtain approval of
zuranolone or that impair the potential profile of zuranolone;
unexpected concerns may arise from additional data, analysis or
results from any of our completed studies; we may encounter adverse
events at any stage of development that negatively impact further
development or that require additional nonclinical and clinical
work which may not yield positive results; we may encounter delays
in initiation, conduct or completion of our planned activities that
may impact our ability to meet our expected timelines; the number
of people with MDD and potential market for zuranolone as a
treatment for MDD, if approved, may be substantially smaller than
our estimates; the unmet need for additional treatment options in
MDD, the potential benefit for zuranolone and market acceptance of
zuranolone, if approved, may not be as significant as we expect;
and we may encounter technical and other unexpected hurdles in the
development and manufacture of zuranolone or any of our other
product candidates which may delay our timing or change our plans
or prospects, or otherwise negatively impact our business; as well
as those risks more fully discussed in the section entitled "Risk
Factors" in our most recent Quarterly Report on Form 10-Q, as well
as 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.
Biogen Safe Harbor This news release contains
forward-looking statements, including statements made pursuant to
the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995, relating to the potential, benefits, safety and
efficacy of zuranolone; the potential clinical effects of
zuranolone; the clinical development program for zuranolone;
clinical development programs, clinical trials and data readouts
and presentations for zuranolone; the potential treatment of MDD;
the potential of Biogen’s commercial business and pipeline
programs, including zuranolone; the anticipated benefits and
potential of Biogen’s collaboration arrangement with Sage; and
risks and uncertainties associated with drug development and
commercialization. These forward-looking statements may be
accompanied by words such as “aim,” “anticipate,” “believe,”
“could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,”
“potential,” “possible,” “will,” “would” and other words and terms
of similar meaning. Drug development and commercialization involve
a high degree of risk and only a small number of research and
development programs result in commercialization of a product.
Results in early-stage clinical trials may not be indicative of
full results or results from later stage or larger scale clinical
trials and do not ensure regulatory approval. You should not place
undue reliance on these statements, or the scientific data
presented.
These statements involve risks and uncertainties that could
cause actual results to differ materially from those reflected in
such statements, including without limitation, uncertainty of
success in the development and potential commercialization of
zuranolone; unexpected concerns may arise from additional data,
analysis or results of clinical studies of zuranolone; regulatory
authorities may require additional information or further studies,
or may fail or refuse to approve or may delay approval of Biogen’s
drug candidates, including zuranolone; the occurrence of adverse
safety events; the risks of other unexpected hurdles, costs or
delays; failure to protect and enforce data, intellectual property
and other proprietary rights and uncertainties relating to
intellectual property claims and challenges; product liability
claims; third party collaboration risks; and the direct and
indirect impacts of the ongoing COVID-19 pandemic on our business,
results of operations and financial condition. The foregoing sets
forth many, but not all, of the factors that could cause actual
results to differ from Biogen’s expectations in any forward-looking
statement. Investors should consider this cautionary statement as
well as the risk factors identified in Biogen’s most recent annual
or quarterly report and in other reports Biogen has filed with the
U.S. Securities and Exchange Commission. These statements are based
on Biogen’s current beliefs and expectations and speak only as of
the date of this news release. Biogen does not undertake any
obligation to publicly update any forward-looking statements,
whether as a result of new information, future developments or
otherwise.
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version on businesswire.com: https://www.businesswire.com/news/home/20220215006261/en/
SAGE MEDIA: Maureen L. Suda (617) 949-4289
Maureen.Suda@sagerx.com
SAGE INVESTORS: Helen Rubinstein (315) 382-3979
Helen.Rubinstein@sagerx.com
BIOGEN MEDIA: Ashleigh Koss Tel: +1 908-205-2572
public.affairs@biogen.com
BIOGEN INVESTORS: Mike Hencke +1 781 464 2442 IR@biogen.com
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