NDA submission for zuranolone for the treatment
of MDD expected to be filed in the second half of 2022, with
rolling submission planned to begin in early 2022
CORAL Study primary endpoint updated, in line
with goal of study to demonstrate rapid reduction in depressive
symptoms and benefits throughout treatment period when co-initiated
with standard antidepressants
Continued pipeline progress demonstrated across
brain health franchises, with plans to initiate three Phase 2
studies across SAGE-324 and SAGE-718 programs
Conference call today at 8:00 a.m. ET
Today, Sage Therapeutics, Inc. (Nasdaq: SAGE), a
biopharmaceutical company committed to developing novel therapies
with the potential to transform the lives of people with
debilitating disorders of the brain, reported business highlights
and financial results for the third quarter ended September 30,
2021.
“I’m proud of the substantial progress we’ve made this quarter,
including a successful pre-NDA meeting with the FDA for zuranolone.
We’re excited to have reached alignment with the Agency and to have
what we believe is a clear, efficient path forward for zuranolone.
We’re now one step closer toward our goal of helping people living
with MDD and PPD by bringing them a treatment that in clinical
development to date has demonstrated rapid and sustained reductions
in depressive symptoms with a well-tolerated safety profile,” said
Barry Greene, chief executive officer at Sage Therapeutics. “It is
an exciting time here at Sage, and I look forward to sharing
additional updates as we progress with our work on the NDA filing
for zuranolone, as well as expected initiation of three new Phase 2
studies for SAGE-324 and SAGE-718.”
Third Quarter 2021 and Recent Portfolio
Updates
Sage is advancing a portfolio of clinical programs featuring
internally discovered novel chemical entities with the potential to
become differentiated products designed to improve brain health by
targeting the GABAA and NMDA receptor systems. Dysfunction in these
systems is thought to be at the core of numerous neurological and
neuropsychiatric disorders.
Depression Franchise
Sage’s depression franchise features zuranolone, Sage’s
next-generation positive allosteric modulator (PAM) of GABAA
receptors being evaluated in clinical development as a treatment
for various affective disorders, and ZULRESSO® (brexanolone) CIV
injection, approved by the U.S. Food and Drug Administration (FDA)
as the first treatment specifically indicated for postpartum
depression (PPD). Zuranolone has received breakthrough therapy
designation from the FDA for the treatment of major depressive
disorder (MDD).
Zuranolone is being evaluated as a potential rapid-acting,
durable, once-daily, two-week treatment for MDD and PPD in the
LANDSCAPE and NEST clinical development programs, respectively.
Sage and Biogen recently announced their plan to submit a New Drug
Application (NDA) to the FDA for zuranolone in the second half of
2022. The planned initial submission package will seek approval of
zuranolone for the treatment of MDD and an additional filing for
PPD is anticipated in the first half of 2023. The decision to
submit the application follows recent discussions with the FDA,
including a pre-NDA meeting held this fall.
The meeting reinforced Sage’s belief that data from the MDD-201,
ROBIN, and WATERFALL Studies and the Shionogi Phase 2 study along
with supportive data from the MOUNTAIN Study will be sufficient for
Sage to file in MDD. The planned initial NDA will focus on MDD and
will also include data from the ongoing pharmacology and clinical
studies (CORAL and SHORELINE Studies). An additional associated NDA
for PPD is expected to be filed following the SKYLARK Study
readout. If planned efforts are successful and zuranolone is
approved, Sage and its collaboration partner, Biogen, plan to
commence marketing for the approved indications as soon as
possible. The review cycles may potentially allow commercialization
of both indications simultaneously, if approved.
Additionally, Sage today announced that the primary endpoint for
the CORAL Study (HAMD-17 change from baseline) will be measured at
Day 3. The CORAL Study is an adjunctive use study in MDD designed
to demonstrate the benefit of zuranolone when co-initiated with a
new antidepressant therapy, including rapid reduction in depressive
symptoms as well as benefits across the treatment period with a
well-tolerated safety profile. The Company believes that, if
successful, the Day 3 primary endpoint and key secondary endpoints,
including other timepoints, will provide additional data that may
be important to inform real world use in MDD if zuranolone is
approved.
In October, Sage and Biogen announced that data presented at the
34th European College of Neuropsychopharmacology (ECNP) Congress
further support the differentiated profile seen to date with
zuranolone in clinical development, including a rapid and sustained
reduction in depressive symptoms and a unique and well-tolerated
safety profile. Further, in a pooled analysis from the LANDSCAPE
and NEST programs, zuranolone treatment led to rapid and sustained
improvement in quality of life and overall health and well-being at
Day 15 that continued to increase through Day 42, as measured by
SF-36v2, a patient self-reported measure of general health. Sage
also presented data at the 34th Psych Congress showing that
zuranolone demonstrated rapid improvements across HAMD-17 subscales
measuring the core symptoms of depression as well as symptoms of
anxiety in the WATERFALL Study. These findings are consistent with
the totality of data across the LANDSCAPE and NEST clinical
programs. As a complement, Sage presented analyses demonstrating
that zuranolone treatment led to rapid improvements in functional
impairment and improvements in depressive symptoms across patient
populations (e.g., age, gender, body mass index) at Day 15 and
regardless of whether patients were receiving zuranolone as
monotherapy or concomitantly with a standard of care
antidepressant.
Sage also announced that it plans to initiate an open-label
study designed to demonstrate the safe-use administration of
ZULRESSO in a patient’s home in the treatment of PPD. The study is
expected to enroll an estimated 50 patients and is anticipated to
be completed in 2022.
The Company expects the following milestones across the
depression franchise in 2021 and 2022:
- Late 2021:
- SHORELINE (MDD-303) Study 50 mg Cohort
(1-year data cut): An open-label Phase 3 study designed to
naturalistically follow patients with MDD and evaluate the safety
and tolerability of zuranolone 50 mg in adults for up to one year.
Topline results from the 1-year data cut of a 50 mg cohort are
expected in late 2021. The SHORELINE Study is expected to remain
open as patients may enroll following their completion of the CORAL
Study.
- Early 2022
- CORAL (MDD-305) Study: A
placebo-controlled Phase 3 study evaluating a two-week course of
zuranolone 50 mg, when co-initiated with a new antidepressant, in
patients with MDD, with additional short-term follow-up. Sage
expects to report topline data in early 2022.
- Mid-2022:
- SKYLARK (PPD-301) Study: Sage
expects to report topline data from the placebo-controlled Phase 3
study evaluating a two-week course of zuranolone 50 mg in women
with PPD, with additional short-term follow-up, in mid-2022.
Neurology Franchise
SAGE-324, a next-generation PAM of GABAA receptors and Sage’s
lead neurology program, is in development as a potential oral
therapy for neurological conditions, such as essential tremor (ET),
epilepsy and Parkinson’s disease (PD).
In the third quarter, Sage and Biogen advanced plans to initiate
a Phase 2 dose-ranging study for SAGE-324 in ET in late 2021 with
the goal of optimizing dosing to maintain plasma concentrations
intended to translate into sustained tremor symptom control. In the
KINETIC Phase 2 placebo-controlled study, SAGE-324 demonstrated a
statistically significant reduction from baseline in the TETRAS
Item 4 upper limb tremor score at Day 29 in the total studied
population compared to placebo and a statistically significant
correlation between TETRAS tremor score and activities of daily
living at all measured time points.
The Company expects the following milestones across the
neurology franchise in 2021:
- Late 2021:
- Phase 2 Study in ET: Sage and
Biogen anticipate initiating a placebo-controlled Phase 2
dose-ranging study in SAGE-324 for ET designed to optimize the dose
and frequency in late 2021.
Neuropsychiatry Franchise
SAGE-718, Sage’s first-in-class NMDA receptor PAM and lead
neuropsychiatric drug candidate, is in development as a potential
oral therapy for cognitive disorders associated with NMDA receptor
dysfunction, potentially including Huntington’s disease (HD),
Parkinson’s disease (PD) and Alzheimer’s disease (AD).
SAGE-718 is currently being studied in the 4-week dosing cohort,
or part B, of the PARADIGM Study, a Phase 2a open-label study in
patients aged 50 to 75 years old with mild cognitive impairment due
to PD and the LUMINARY Study, a Phase 2a open-label study
evaluating SAGE-718 in patients with AD mild cognitive impairment
and mild dementia.
In the third quarter, SAGE-718 received Fast Track Designation
for development as a potential treatment for HD. The Company plans
to initiate a placebo-controlled Phase 2 study of SAGE-718 in
patients with early to moderate HD in late 2021. Also, Sage today
announced plans to initiate a second placebo-controlled Phase 2
Study with SAGE-718 in patients with PD mild cognitive impairment
in 2022.
The Company expects the following milestones across the
neuropsychiatry franchise in 2021 and 2022:
- Late 2021:
- LUMINARY (718-CNA-201)
Study: The LUMINARY Study is fully enrolled, and the
Company anticipates topline data from the study in late 2021.
- Phase 2 Study in HD: The Company
is on track to initiate a placebo-controlled Phase 2 study with
SAGE-718 in early to moderate HD in late 2021.
- 2022:
- Phase 2 Study in PD: The Company
plans to initiate a placebo-controlled Phase 2 Study with SAGE-718
in PD mild cognitive impairment in 2022.
Early Development
Sage expects to complete certain ongoing Phase 1 clinical
studies for two programs in its early development pipeline in late
2021, SAGE-689 (single ascending dose) and SAGE-904 (single
ascending dose). The multiple ascending dose study for SAGE-904 is
also ongoing. Results from the Phase 1 studies will inform further
development of these programs.
- SAGE-689: an intramuscular GABAA receptor PAM in
development as a potential therapy for disorders associated with
acute GABA hypofunction. The first patient was dosed in the
SAGE-689 Phase 1 single ascending dose study earlier this
year.
- SAGE-904: Sage’s second NMDA receptor PAM product
candidate in development as a potential oral therapy for disorders
associated with NMDA hypofunction. The first patient was dosed in
the continued SAGE-904 Phase 1 studies earlier this year.
Additionally, IND-enabling work is underway for SAGE-319.
- SAGE-319: an oral, extrasynaptic GABAA receptor
preferring PAM that Sage plans to study for potential use in
disorders of social interaction.
The Company now plans to advance SAGE-421 to preclinical studies
in 2022.
- SAGE-421: an oral, NMDA receptor PAM that Sage plans to
study for potential use in neurodevelopmental disorders and
cognitive recovery and rehabilitation.
Business Updates
During the third quarter, the Company strengthened its
leadership with key changes:
- Chris Benecchi, MBA, joined Sage as Chief Commercial Officer.
Chris will lead Sage’s global commercial efforts across all Sage
programs, new product planning, strategy, and competitive
intelligence.
- Jim Doherty, Ph.D., assumed the role of Chief Development
Officer. Jim will continue to drive expansion and acceleration of
Sage’s development programs and lead the Research and Development
Leadership Team.
- Mike Quirk, Ph.D., promoted to Senior Vice President of
Discovery Research. As part of his new role, Mike will continue to
build the necessary research expertise to position Sage to deliver
on the Company’s goal of delivering two IND enabling programs per
year by 2023. Mike brings more than 20 years of experience in
biopharmaceutical drug discovery and development solving biological
and translational science problems in psychiatry, neurology, and
pain.
- Vanessa Procter promoted to Senior Vice President, External
Affairs and joined the executive leadership team. As part of her
new role, Vanessa will build and lead a new external affairs
capability within Sage. Vanessa has more than 20 years of
experience navigating corporate policy, advocacy, and political
spheres to deliver tangible business results.
- Steve Kanes, M.D., resigned as Sage’s Chief Medical Officer.
Steve is pursuing a new opportunity as a Chief Executive Officer at
a private biotechnology company.
ANTICIPATED 2021 AND 2022
MILESTONES
Late 2021:
- Zuranolone:
- Report topline data cut from Phase 3 SHORELINE Study 50 mg
cohort in MDD
- SAGE-324:
- Initiate Phase 2 dose-ranging study in ET
- SAGE-718:
- Report topline data from Phase 2a LUMINARY open-label, signal
finding study in patients with AD mild cognitive impairment and
mild dementia
- Initiate placebo-controlled Phase 2 study in early to moderate
HD
2022:
- Zuranolone:
- Report topline data from the CORAL Study (early 2022)
- Report topline data from the SKYLARK Study (mid-2022)
- Submit NDA filing package for zuranolone for the treatment of
MDD (2H 2022) with rolling submission starting early 2022
- SAGE-718:
- Initiate placebo-controlled Phase 2 study in PD
FINANCIAL RESULTS FOR THE THIRD QUARTER
OF 2021
- Cash Position: Cash, cash equivalents and marketable
securities as of September 30, 2021 were $1.8 billion compared to
$1.9 billion at June 30, 2021.
- Revenue: Net revenue from sales of ZULRESSO was $1.4
million in the third quarter of 2021 compared to $1.6 million in
the same period of 2020.
- R&D Expenses: Research and development expenses were
$83.5 million, including $17.9 million of non-cash stock-based
compensation expense, in the third quarter of 2021 compared to
$74.1 million, including $9.9 million of non-cash stock-based
compensation expense, for the same period in 2020, an increase of
$9.4 million. The amount for the third quarter of 2021 reflects an
increase in expenses of $31.0 million and a reduction in expenses
of $21.6 million due to reimbursement from Biogen pursuant to the
Sage/Biogen Collaboration and License Agreement. The primary
reasons for the increase in expenses were manufacturing-related
activities for zuranolone, work on studies that began in 2021, work
on research activities, an increase in hiring and non-cash
stock-based compensation expense based on the determination that
the achievement of a milestone for vesting of certain outstanding
performance restricted stock units was considered probable.
- SG&A Expenses: Selling, general and administrative
expenses were $48.7 million, including $16.5 million of non-cash
stock-based compensation expense, in the third quarter of 2021
compared to $35.1 million, including $10.2 million of non-cash
stock-based compensation expense, for the same period in 2020, an
increase of $13.6 million. The amount for the third quarter of 2021
reflects an increase in expenses of $16.4 million and a reduction
in expenses of $2.8 million due to reimbursement from Biogen
pursuant to the Sage/Biogen Collaboration and License Agreement.
The primary reasons for the increase in expenses were an increase
in hiring and non-cash stock-based compensation expense based on
the determination that the achievement of a milestone for vesting
of certain outstanding performance restricted stock units was
considered probable.
- Net Loss: Net loss was $130.2 million for the third
quarter of 2021 compared to $105.7 million for the same period of
2020.
FINANCIAL GUIDANCE
- Sage anticipates cash, cash equivalents and marketable
securities of more than $1.7 billion at the end of 2021.
- The Company does not anticipate receipt of any milestone
payments from collaborations in 2021.
Conference Call Information
Sage will host a conference call and webcast today, Tuesday,
November 2, at 8:00 a.m. ET to discuss its third quarter 2021
financial results and recent corporate updates. 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 Sage Therapeutics
Sage Therapeutics is a biopharmaceutical company committed to
developing novel therapies with the potential to transform the
lives of people with debilitating disorders of the brain. We are
pursuing new pathways with the goal of improving brain health, and
our depression, neurology and neuropsychiatry franchise programs
aim to change how brain disorders are thought about and treated.
Our mission is to make medicines that matter so people can get
better, sooner. 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
statements regarding: plans for an NDA filing and associated
submission for zuranolone in MDD and PPD, and the potential timing
of such submissions; our belief in the adequacy of the data we plan
to include in the zuranolone NDA; the potential for FDA acceptance
of an NDA for zuranolone; our belief in the regulatory filing
pathways for zuranolone; the potential profile and benefit of
zuranolone in MDD and PPD; the potential for regulatory approval
and commencement of commercialization of zuranolone and our belief
as to the potential to commence commercialization of both
indications, if approved, in parallel; other planned next steps for
the program; anticipated timelines for reporting clinical trial
results, commencement of trials, and initiation of new activities;
our plans for advancement of our pipeline; our belief in the
potential profile and benefit of our product candidates; potential
indications for our product candidates; the potential for success
of our programs, and the opportunity to help patients in various
indications; the mission and goals for our business and potential
value creation opportunities; and our expectations with respect to
2021 year-end cash. 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 submit an NDA for zuranolone
and we may not be able to submit the NDA on the timelines we expect
or at all; the FDA may find inadequacies and deficiencies in our
NDA for zuranolone, including in the data we submit, despite prior
discussions, and may decide not to accept the NDA for filing; even
if the FDA accepts the NDA for filing, 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; the FDA may not meet expected review
timelines for our NDA; 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; success in earlier
clinical trials of any of our product candidates may not be
repeated or observed in ongoing or future studies, and ongoing and
future clinical trials may not meet their primary or key secondary
endpoints which may substantially impair development; 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 ongoing and planned clinical trials,
including as a result of slower than expected site initiation or
enrollment, the need or decision to expand the trials or other
changes, that may impact our ability to meet our expected timelines
and increase our costs; 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 or may impair the potential for
successful development; the anticipated benefits of our ongoing
collaborations may never be achieved and the need to align with our
collaborators may hamper or delay our development and
commercialization efforts or increase our costs; our business may
be adversely affected and our costs may increase if any of our key
collaborators fails to perform its obligations or terminates our
collaboration; the internal and external costs required for our
ongoing and planned activities, and the resulting impact on expense
and use of cash, may be higher than expected which may cause us to
use cash more quickly than we expect or change or curtail some of
our plans or both; we may never be able to generate meaningful
revenues from sales of ZULRESSO or to generate revenues at levels
we expect or at levels necessary to justify our investment; our
expectations as to year-end cash may prove not to be correct for
other reasons such as changes in plans or actual events being
different than our assumptions; we may be opportunistic in our
future financing plans even if available cash is sufficient;
additional funding may not be available on acceptable terms when we
need it; the number of patients with the diseases or disorders for
which our products are developed, the unmet need for additional
treatment options and the potential market for our current or
future products may be significantly smaller than we expect; and we
may encounter technical and other unexpected hurdles in the
development and manufacture of our product candidates or the
commercialization of our marketed product which may delay our
timing or change our plans, increase our costs 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.
Sage Therapeutics, Inc. and Subsidiaries Condensed
Consolidated Statements of Operations (in thousands, except
share and per share data) (unaudited)
Three Months Ended
September 30, Nine Months Ended September 30,
2021
2020
2021
2020
Product revenue, net
$
1,440
$
1,639
$
4,666
$
5,014
Operating costs and expenses: Cost of goods sold
131
149
466
429
Research and development
83,497
74,078
207,723
211,008
Selling, general and administrative
48,706
35,099
131,899
143,454
Restructuring
-
(529
)
-
27,873
Total operating costs and expenses
132,334
108,797
340,088
382,764
Loss from operations
(130,894
)
(107,158
)
(335,422
)
(377,750
)
Interest income, net
692
1,347
2,132
8,763
Other income, net
31
76
110
165
Net loss
$
(130,171
)
$
(105,735
)
$
(333,180
)
$
(368,822
)
Net loss per share - basic and diluted
$
(2.21
)
$
(2.03
)
$
(5.69
)
$
(7.10
)
Weighted average shares outstanding - basic and diluted
58,819,548
51,981,468
58,593,743
51,938,923
Sage Therapeutics, Inc. and Subsidiaries Condensed
Consolidated Balance Sheets (in thousands) (unaudited)
September 30,2021 December 31,2020 Cash, cash
equivalents and marketable securities
$
1,843,169
$
2,099,549
Total assets
$
1,927,180
$
2,159,246
Total liabilities
$
91,526
$
86,912
Total stockholders' equity
$
1,835,654
$
2,072,334
ZULRESSO (brexanolone) SELECT IMPORTANT SAFETY
INFORMATION
This does not include all the information needed to use ZULRESSO
safely and effectively. See full prescribing information for
ZULRESSO.
WARNING: EXCESSIVE SEDATION AND SUDDEN LOSS OF
CONSCIOUSNESS
See full prescribing information for complete boxed warning
Patients are at risk of excessive sedation or sudden loss of
consciousness during administration of ZULRESSO.
Because of the risk of serious harm, patients must be
monitored for excessive sedation and sudden loss of consciousness
and have continuous pulse oximetry monitoring. Patients must be
accompanied during interactions with their child(ren).
ZULRESSO is available only through a restricted program
called the ZULRESSO REMS.
WARNINGS AND PRECAUTIONS
Suicidal Thoughts and Behaviors: Consider changing the
therapeutic regimen, including discontinuing ZULRESSO, in patients
whose PPD becomes worse or who experience emergent suicidal
thoughts and behavior.
ADVERSE REACTIONS: Most common adverse reactions
(incidence ≥5% and at least twice the rate of placebo) were
sedation/somnolence, dry mouth, loss of consciousness, and
flushing/hot flush.
USE IN SPECIFIC POPULATIONS
• Pregnancy: ZULRESSO may cause fetal harm. Healthcare
providers are encouraged to register patients by calling the
National Pregnancy Registry for Antidepressants at 1-844-405-6185
or visiting online at
https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/
• Renal Impairment: Avoid use of ZULRESSO in patients
with end stage renal disease (ESRD)
Controlled Substance: ZULRESSO contains brexanolone, a
Schedule IV controlled substance under the Controlled Substances
Act.
To report SUSPECTED ADVERSE REACTIONS, contact Sage
Therapeutics, Inc. at 1-844-4-SAGERX (1-844-472-4379) or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
Please see accompanying full Prescribing Information
including Boxed Warning.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20211102005276/en/
Investor Contact Helen Rubinstein 315-382-3979
helen.rubinstein@sagerx.com
Media Contact Maureen L. Suda 617-949-4289
maureen.suda@sagerx.com
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