U.S. Food and Drug Administration (FDA) accepts
filing of New Drug Application (NDA) for zuranolone and grants
Priority Review in the treatment of Major Depressive Disorder (MDD)
and Postpartum Depression (PPD) following submission of rolling NDA
in December 2022
Robust pipeline advancing nine studies across
neuropsychiatry and neurology in 2023
Year-end 2022 cash, cash equivalents and
marketable securities of $1.3 billion along with ongoing
collaboration funding, and potential revenue, expected to support
operations into 2025
Sage Therapeutics, Inc. (Nasdaq: SAGE), a biopharmaceutical
company leading the way to create a world with better brain health,
today reported business highlights and financial results for the
fourth quarter and full year ended December 31, 2022.
“We set out in 2022 to deliver on a bold agenda; starting with
the goal of transforming the treatment of depression. We have been
laser focused on the opportunity to help millions of people who are
desperate for new treatment options and the recent acceptance of
the NDA filing for zuranolone in MDD and PPD puts us one step
closer to that goal,” said Barry Greene, Chief Executive Officer at
Sage Therapeutics. “We are also progressing a promising and
targeted pipeline with the goal of being able to launch new drugs
or indications for years to come. This momentum puts us in a
position of strength as we kick off 2023 and progress in our plan
to become the leader in brain health and a top tier
biopharmaceutical company.”
Key 2022 Highlights
Advanced Regulatory Path and Commercialization Plans for
Zuranolone: In December 2022, Sage and its collaborator Biogen
announced the completion of the rolling NDA submission for
zuranolone in MDD and PPD. Sage and Biogen recently announced that
the FDA accepted the filing of the NDA for zuranolone and that the
application was granted Priority Review, with a Prescription Drug
User Fee Act (PDUFA) action date of August 5, 2023.
- The NDA submission includes data from the LANDSCAPE and NEST
clinical development programs as well as a Phase 2 study of
zuranolone completed by Shionogi in Japan in adults with MDD for
zuranolone. The LANDSCAPE program includes five studies of
zuranolone in adults with MDD (MDD-201B, MOUNTAIN, SHORELINE,
WATERFALL, and CORAL Studies). The NEST program includes two
studies of zuranolone in adult women with PPD (ROBIN and SKYLARK
Studies). Zuranolone, if approved, could represent the first oral,
short course (14-day) medication with rapid onset for MDD and
PPD.
- In 2022, Sage and Biogen advanced commercialization plans for
zuranolone through scientific exchange, permitted interactions with
payers and disease state education in MDD and PPD. Sage expects
these efforts and other permitted pre-launch activities to advance
in 2023.
Reported Positive Topline Data from Phase 3 SKYLARK Study in
2022 and Multiple Data Presentations Supporting Zuranolone
Potential: Sage and its collaborator Biogen announced positive
topline data from the SKYLARK Study in 2022. The companies also
presented multiple datasets from the LANDSCAPE and NEST clinical
development programs that support the potential efficacy and safety
of zuranolone for the treatment of MDD and PPD, respectively.
- The Phase 3 SKYLARK Study of zuranolone in PPD met its primary
endpoint and all key secondary endpoints, demonstrating significant
and clinically meaningful improvement in depressive symptoms as
early as day 3 for participants treated with zuranolone 50mg, which
was sustained at all measured timepoints through day 45.
- Multiple new analyses across the zuranolone development program
were presented at key congresses throughout the year, including new
analyses from the SHORELINE Study and Health Economics and Outcomes
Research.
- Across the clinical program in MDD and PPD, zuranolone showed
consistent rapid and sustained improvement of depressive symptoms
with a generally well-tolerated and consistent safety profile.
Presented Encouraging Data from Phase 2 Open Label LUMINARY
and Open Label PARADIGM Studies of SAGE-718: SAGE-718
demonstrated improvements across multiple domains of cognition,
including executive performance and learning and memory, in
patients with mild cognitive impairment (MCI) and mild dementia due
to Alzheimer’s disease (AD) in the Phase 2 open-label LUMINARY
Study and in patients with mild cognitive impairment (MCI) due to
Parkinson’s disease (PD) in the Phase 2 open-label PARADIGM
Study.
- Data from the Phase 2 open-label PARADIGM Study (Part A, 14
days of dosing) presented at the AD/PD 2022 Advances in Science
& Therapy International Conference on Alzheimer’s and
Parkinson’s Diseases and Related Neurological Disorders, showed
that SAGE-718 was associated with improvements in executive
function and learning and memory at Day 14 in patients with MCI due
to PD. Additionally, sustained effects and improving trends were
observed at 14 days post-treatment.
- Additional results from the Phase 2 open-label PARADIGM Study
(Part B, 28 days of dosing) were presented at ECNP and showed that
improvements in executive function could be sustained through 28
days of dosing.
- Data from the Phase 2 open-label LUMINARY Study in individuals
with MCI and mild dementia due to AD presented at the American
Academy of Neurology showed that SAGE-718 given once daily for 14
days was generally well-tolerated and associated with improved
executive performance and learning and memory.
- SAGE-718 has been well-tolerated in studies to date.
Strengthened Executive Leadership Team: In 2022, the
Company strengthened its leadership team with several key
appointments including Laura M. Gault, M.D., Ph.D. as Chief Medical
Officer and Mark Pollack, M.D. as Senior Vice President, Medical
Affairs. Sage also made key leadership hires, further building out
the commercial team.
Fourth Quarter 2022 Portfolio
Updates
Sage is advancing a portfolio of clinical-stage 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
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 FDA as the first treatment specifically
indicated for PPD. Zuranolone has received Breakthrough Therapy and
Fast Track Designation for the treatment of MDD and Fast Track
Designation for the treatment of PPD from the FDA.
Zuranolone is being evaluated as a potential rapid-acting,
once-daily, oral two-week treatment for MDD and PPD. Across the
LANDSCAPE and NEST clinical development programs to date,
zuranolone has demonstrated rapid and sustained relief of
depressive symptoms in people with MDD and PPD. In December 2022,
Sage and its collaborator Biogen completed the rolling NDA
submission for zuranolone in MDD and PPD. The companies recently
announced the NDA for zuranolone was accepted for filing by the FDA
and granted priority review with a PDUFA action date of August
5th.
The Company expects the following milestones across the
depression franchise in 2023:
- Mid 2023:
- Present additional data from the SHORELINE Study
- Late 2023:
- PDUFA date for zuranolone in MDD and PPD (August 5th)
- Commercial availability of zuranolone in MDD and PPD, if
zuranolone is approved with no review extensions
- Initiate a lifecycle innovation study with zuranolone
- Present additional analyses of data from LANDSCAPE and NEST
clinical programs, including health economics and patient reported
outcomes
Neuropsychiatry
Sage’s neuropsychiatry franchise features SAGE-718, the
Company’s first-in-class NMDA receptor PAM and lead
neuropsychiatric drug candidate, 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
received Fast Track Designation from the FDA for the potential
treatment of HD.
Sage is advancing a robust clinical program for SAGE-718 with
multiple ongoing or planned Phase 2 studies across multiple disease
areas, including its potential lead indication, cognitive
impairment associated with HD, as well as cognitive impairment due
to AD and PD. The Company recently initiated LIGHTWAVE (CNA-202), a
Phase 2 study of SAGE-718 in people with mild cognitive impairment
and mild dementia due to AD and PURVIEW (CIH-301), a Phase 3
extension study in people with cognitive impairment due to HD.
Sage is currently enrolling in the following studies:
- DIMENSION (CIH-201) Study: The
DIMENSION Study is a double-blind, placebo-controlled Phase 2 study
in people with HD cognitive impairment. The study is designed to
evaluate the efficacy of once-daily SAGE-718 dosed over three
months, with a target enrollment of approximately 178 people. Sage
expects the DIMENSION Study to include more than 40 clinical
sites.
- SURVEYOR (CIH-202) Study: The
SURVEYOR Study is a double-blind, placebo-controlled Phase 2 study
in people with HD cognitive impairment and healthy volunteers, with
the goal of generating evidence linking efficacy signals on
cognitive performance to domains of real-world functioning.
- PURVIEW (CIH-301) Study: The
PURVIEW Study is an open-label Phase 3 safety study of SAGE-718 in
people with HD cognitive impairment. The study is designed to
evaluate the long-term safety profile and benchmark performance
against HD natural history studies.
- PRECEDENT (CNP-202) Study: The
PRECEDENT Study is a double-blind, placebo-controlled Phase 2 study
in people with MCI due to PD. The study is designed to evaluate the
safety and efficacy of SAGE-718 in people with MCI due to PD over
42 days, followed by a controlled follow-up period.
- LIGHTWAVE (CNA-202) Study: The
LIGHTWAVE Study is a double-blind, placebo-controlled Phase 2 study
of SAGE-718 in people with MCI and mild dementia due to AD. The
study is designed to evaluate the safety and efficacy of SAGE-718
dosed over an 84-day period (across an initial dose and a lower
dose), followed by a controlled follow-up period.
The Company expects the following milestones across the
neuropsychiatry franchise in 2023:
- Progress recruitment in the ongoing DIMENSION, SURVEYOR,
PURVIEW, PRECEDENT, and LIGHTWAVE Studies
- Present additional analyses of data from clinical development
program as well as disease state and burden of disease research in
Huntington's, Parkinson’s and Alzheimer’s diseases
Neurology
Sage’s neurology franchise features SAGE-324 and SAGE-689.
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 PD. SAGE-689 is an intramuscular GABAA receptor PAM in
development as a potential therapy for disorders associated with
acute GABA hypofunction.
Sage and its collaborator, Biogen, are currently enrolling
participants in the Phase 2b KINETIC 2 placebo-controlled study of
SAGE-324 in ET following positive results from the KINETIC Study.
The KINETIC 2 Study is a Phase 2b dose-ranging study with the
primary goal of defining the dose for SAGE-324 in ET with a good
tolerability profile and a dosing schedule to maintain plasma
concentrations needed for sustained tremor symptom control in
treating ET. Enrollment in the KINETIC 2 Study is expected to be
completed in late 2023.
Sage is also currently dosing patients in a Phase 2 long-term
open label safety study, to evaluate the long-term safety and
tolerability of SAGE-324 in ET. The primary endpoint is incidence
of treatment-emergent adverse events.
SAGE-689 continues in Phase 1 development.
The Company expects the following milestones across the
neurology franchise in 2023:
Late 2023:
- Anticipate completion of enrollment in the Phase 2b KINETIC 2
Study
- Present additional analyses of data from clinical development
program as well as disease state and burden of disease research in
ET
Early Development
Sage is progressing its early development programs, SAGE-319 and
SAGE-421. IND-enabling work is underway for SAGE-421 and the
Company plans to move SAGE-319 to Phase 1 studies.
- SAGE-319: an oral, extra-synaptic GABAA receptor
preferring PAM that Sage plans to study for potential use in
disorders of social interaction.
- SAGE-421: an oral, NMDA receptor PAM that Sage plans to
study for potential use in neurodevelopmental disorders and
cognitive recovery and rehabilitation.
FINANCIAL RESULTS FOR THE FOURTH
QUARTER AND FULL YEAR 2022
- Cash Position: Cash, cash equivalents and marketable
securities as of December 31, 2022 were $1.3 billion compared to
$1.4 billion at September 30, 2022.
- Revenue: Net revenue from sales of ZULRESSO was $2.9
million in the fourth quarter of 2022, compared to $1.6 million in
the same period of 2021. For the year ended December 31, 2022, net
revenue from sales of ZULRESSO was $7.7 million compared to $6.3
million in the same period of 2021.
- R&D Expenses: Research and development expenses were
$89.3 million, including $4.9 million of non-cash stock-based
compensation expense, in the fourth quarter of 2022 compared to
$75.4 million, including $9.1 million of non-cash stock-based
compensation expense, for the same period in 2021. For the year
ended December 31, 2022, R&D expenses were $326.2 million,
including $25.9 million of non-cash stock-based compensation
expense, compared to $283.2 million, including $49.7 million of
non-cash stock-based compensation expense, for the same period in
2021. For the year, the increase in R&D expenses was primarily
due to increased spending on SAGE-324 and Sage’s wholly owned
pipeline, including SAGE-718 and other programs. Increases were
partially offset by the completion of the WATERFALL Study and the
CORAL Study for zuranolone and decreases in non-cash stock-based
compensation expense. The reimbursement from Biogen for R&D
expenses pursuant to the Sage/Biogen Collaboration and License
Agreement was $73.2 million in 2022 compared to $79.8 million in
the same period of 2021.
- SG&A Expenses: Selling, general and administrative
expenses were $67.3 million, including $10.4 million of non-cash
stock-based compensation expense, in the fourth quarter of 2022,
compared to $51.6 million, including $11.5 million of non-cash
stock-based compensation expense, for the same period in 2021. For
the year ended December 31, 2022, SG&A expenses were $227.7
million, including $35.7 million of non-cash stock-based
compensation expense, compared to $183.5 million, including $54.9
million of non-cash stock-based compensation expense, for the same
period in 2021. The increase in SG&A expenses was primarily due
to hiring employees to support ongoing activities in anticipation
of the potential launch of zuranolone. The reimbursement from
Biogen for SG&A expenses pursuant to the Sage/Biogen
Collaboration and License Agreement was $2.2 million in 2022
compared to $11.3 million in the same period of 2021.
- Net Loss: Net loss was $147.1 million for the fourth
quarter of 2022 compared to $124.7 million for the same period in
2021. For the year ended December 31, 2022, net loss was $532.8
million compared to $457.9 million for the same period in
2021.
FINANCIAL GUIDANCE
- Based upon the Company's current operating plan, Sage
anticipates that its existing cash, cash equivalents and marketable
securities, anticipated funding from ongoing collaborations, and
potential revenue, will support its operations into 2025.
- This includes the potential to achieve milestones totaling
$225.0 million from Biogen related to first commercial sales of
zuranolone in MDD and PPD in the U.S., if approved.
- The Company anticipates R&D and SG&A spending to
increase as it prepares for the potential launch of zuranolone and
advances planned and ongoing studies for SAGE-718 and
SAGE-324.
Conference Call Information
Sage will host a conference call and webcast today, Thursday,
February 16, at 8:00 a.m. ET to review its fourth quarter and full
year 2022 financial results and discuss 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 following the completion of the event
and will be archived for up to 30 days.
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 http://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: the potential profile and benefit of
zuranolone in MDD and PPD; the potential for regulatory approval
and commencement of launch and commercialization of zuranolone and
potential timing of such activities; our belief in our readiness
for commercial launch of zuranolone, if approved; other planned
next steps for the zuranolone program and planned commercialization
activities; anticipated timelines for commencement of trials,
completion of dosing, initiation of new activities and other plans
for our other programs and early stage 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 our
expectations with respect to potential receipt of milestones from
collaborations, funding of future operations and increases in
expenses. 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: the FDA may find that the data included in our NDA for
zuranolone are not sufficient for approval and may not approve the
NDA in MDD or PPD, or both, or may approve zuranolone for only a
subset of such patients; 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, results and expected timelines;
results of ongoing or future studies may impact our ability to
obtain approval of zuranolone or impair the potential profile of
zuranolone; success in earlier clinical trials of any of our other
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 that negatively impact
further development, the potential for approval or the potential
for successful commercialization of any our product candidates or
that require additional nonclinical and clinical work which may not
yield positive results; we may encounter delays in initiation,
conduct, completion of enrollment or completion of our ongoing and
planned clinical trials, including as a result of slower than
expected site initiation, slower than expected 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, including the
achievement of events tied to milestone payments or the successful
development or commercialization of products and generation of
revenue, may never be achieved; 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; we may
not be successful in our efforts to gain regulatory approval of
products beyond ZULRESSO; we may not achieve revenues from
zuranolone, if approved, or any other of our products that may be
successfully developed, at the levels we expect; our expectations
as to sufficiency of cash to fund future operations and expense
levels may prove not to be correct for these and 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 zuranolone or any
of our other products are developed, the unmet need for additional
treatment options, and the potential market for zuranolone, if
approved, or any other future products, if successfully developed,
may be significantly smaller than we expect; zuranolone, if
approved or any of our other products that may be successfully
developed in the future may not achieve the clinical benefit,
clinical use or market acceptance we expect or we may encounter
reimbursement-related or other market-related issues that impact
the success of our commercialization efforts; and we may encounter
technical and other unexpected hurdles in the development and
manufacture of our product candidates or the commercialization of
any current or future 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, 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.
Financial Tables
Sage Therapeutics, Inc. and Subsidiaries Condensed
Consolidated Statements of Operations (in thousands, except
share and per share data) (unaudited)
Three Months Ended December
31,
Year Ended December
31,
2022
2021
2022
2021
Product revenue, net
$
2,865
$
1,642
$
7,686
$
6,308
Operating costs and expenses: Cost of goods sold
143
87
813
553
Research and development
89,295
75,443
326,163
283,166
Selling, general and administrative
67,329
51,599
227,699
183,498
Total operating costs and expenses
156,767
127,129
554,675
467,217
Loss from operations
(153,902
)
(125,487
)
(546,989
)
(460,909
)
Interest income, net
6,793
751
14,190
2,883
Other income (expense), net
(37
)
24
15
134
Net loss
$
(147,146
)
$
(124,712
)
$
(532,784
)
$
(457,892
)
Net loss per share - basic and diluted
$
(2.47
)
$
(2.12
)
$
(8.98
)
$
(7.80
)
Weighted average shares outstanding - basic and diluted
59,494,613
58,897,195
59,306,094
58,670,230
Sage Therapeutics, Inc. and Subsidiaries Condensed
Consolidated Balance Sheets (in thousands) (unaudited)
December 31,2022 December 31,2021 Cash, cash
equivalents and marketable securities
$
1,272,494
$
1,742,296
Total assets
$
1,356,449
$
1,825,288
Total liabilities
$
103,850
$
96,257
Total stockholders' equity
$
1,252,599
$
1,729,031
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/20230215005948/en/
Investor Contact Helen Rubinstein 315-382-3979
helen.rubinstein@sagerx.com
Media Contact Matthew Henson 917-930-7147
matthew.henson@sagerx.com
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