New Drug Application (NDA) for zuranolone in
the treatment of Major Depressive Disorder (MDD) and Postpartum
Depression (PPD) under priority review by U.S. Food and Drug
Administration (FDA) with a PDUFA date of August 5, 2023
Sage and Biogen progressing key commercial
preparations to support a potential launch of zuranolone in late
2023, following DEA scheduling period, if approved and expected
timelines are met
Continued progress across pipeline with nine
studies advancing across neuropsychiatry and neurology
Data demonstrating severe economic burden
associated with depression presented at the Academy of Managed Care
Pharmacy and The Professional Society for Health Economics and
Outcomes Research
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
first quarter ended March 31, 2023.
“The first quarter was marked by important advancements across
our brain health pipeline and product engine, which lay the
groundwork for continued execution and the potential for long-term
value creation, particularly as we approach the PDUFA target action
date for zuranolone in MDD and PPD,” said Barry Greene, Chief
Executive Officer at Sage Therapeutics. “We are laser focused on
progressing launch readiness activities in collaboration with
Biogen and we believe that our planned strategic approach to the
commercialization of zuranolone, if approved, will help us to
achieve our vision of transforming the way depression is
treated.”
First Quarter 2023 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 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 14-day 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 February 2023,
Sage and Biogen announced the FDA accepted the filing of an NDA for
zuranolone for the treatment of MDD and PPD. The application was
granted priority review and assigned a Prescription Drug User Fee
Act (PDUFA) action date of August 5, 2023.
In March, Sage and Biogen presented important health economics
and outcomes research at the Academy of Managed Care Pharmacy
Annual Meeting that reinforced the significant negative impacts MDD
can have on patients, their families and society. These
presentations highlighted the associations between MDD symptoms and
reduced health-related quality of life scores, and the burden that
extends to other adults living in a home with someone with MDD.
They also showed the increase in all-health related and MDD-related
costs during the 90-day period following treatment with a current
antidepressant.
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, and following DEA
scheduling period
- 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 has
received Fast Track Designation from the FDA and Orphan Drug
Designation from the European Medicines Agency (EMA) for the
potential treatment of HD.
Sage is advancing a robust clinical program for SAGE-718 with
ongoing studies across multiple disease areas, including cognitive
impairment associated with HD as well as cognitive impairment due
to AD and PD.
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 mild cognitive impairment 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, 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 on 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 movement disorders, such as essential tremor (ET), epilepsy and
PD. SAGE-689, a Sage wholly-owned program, is an intramuscular
balanced GABAA receptor PAM in development as a potential therapy
for disorders associated with GABA hypofunction.
Sage and its collaborator, Biogen, are actively 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 targeted for
completion in late 2023.
Sage is also currently enrolling 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:
- Targeted 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 continues to progress its early development programs,
SAGE-319 and SAGE-421. SAGE-319 is currently in Phase 1 studies and
IND-enabling work is underway for SAGE-421.
- SAGE-319: an oral, extra-synaptic preferring GABAA
receptor 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 FIRST QUARTER
2023
- Cash Position: Cash, cash equivalents and marketable
securities as of March 31, 2023 were $1.1 billion compared to $1.3
billion at December 31, 2022.
- Revenue: Net revenue from sales of ZULRESSO was $3.3
million in the first quarter of 2023 compared to $1.6 million in
the same period of 2022.
- R&D Expenses: Research and development expenses were
$92.8 million, including $8.8 million of non-cash stock-based
compensation expense, in the first quarter of 2023 compared to
$78.0 million, including $8.6 million of non-cash stock-based
compensation expense, in the same period of 2022. The increase in
spending was primarily due to an increase in the hiring of
employees and corporate infrastructure costs, such as information
technology costs, to support the growth in our research and
development operations. The reimbursement from Biogen to us for
R&D expenses pursuant to the Sage/Biogen Collaboration and
License Agreement was $17.3 million in the first quarter of 2023
compared to $18.5 million in the same period of 2022.
- SG&A Expenses: Selling, general and administrative
expenses were $65.7 million, including $11.3 million of non-cash
stock-based compensation expense, in the first quarter of 2023
compared to $46.5 million, including $9.9 million of non-cash
stock-based compensation expense, in the same period of 2022. The
increase in SG&A expenses was primarily due to hiring employees
to support ongoing activities in anticipation of potential launch
of zuranolone. The reimbursement from us to Biogen for SG&A
expenses pursuant to the Sage/Biogen Collaboration and License
Agreement was $3.0 million in the first quarter of 2023 compared to
$1.5 million of reimbursement from Biogen to us in the same period
of 2022.
- Net Loss: Net loss was $146.8 million in the first
quarter of 2023 compared to $122.1 million in the same period of
2022.
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 for the treatment of 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, Tuesday, May
2, at 8:00 a.m. ET to review its first quarter 2023 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 potential for value creation opportunities; the
mission and goals for our business; and our expectations with
respect to potential receipt of milestones from collaborations,
potential future revenue, cash runway; 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 or with limitations or restrictions; 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 or may find other
deficiencies in our development program, data, processes, or
manufacturing sites that causes the FDA not to approve our NDA; the
FDA 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 or may impose review extensions; 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 for any of our products or
product candidates at any stage that negatively impact further
development, the potential for approval or the potential for
successful commercialization 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 to 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 cash run-way, the 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
for 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
March 31,
2023
2022
Product revenue, net
$
3,294
$
1,582
Operating costs and expenses: Cost of goods sold
230
286
Research and development
92,826
78,018
Selling, general and administrative
65,708
46,477
Total operating costs and expenses
158,764
124,781
Loss from operations
(155,470
)
(123,199
)
Interest income, net
8,830
1,168
Other expense, net
(188
)
(24
)
Net loss
$
(146,828
)
$
(122,055
)
Net loss per share - basic and diluted
$
(2.46
)
$
(2.07
)
Weighted average shares outstanding - basic and diluted
59,674,127
59,028,858
Sage Therapeutics, Inc. and Subsidiaries Condensed
Consolidated Balance Sheets (in thousands) (unaudited)
March 31,2023 December 31,2022 Cash, cash equivalents
and marketable securities
$
1,129,585
$
1,272,494
Total assets
1,220,686
1,356,449
Total liabilities
87,557
103,850
Total stockholders' equity
1,133,129
1,252,599
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/20230501005482/en/
Investor: Helen Rubinstein 315-382-3979 helen.rubinstein@sagerx.com
Media: Matthew Henson 917-930-7147
matthew.henson@sagerx.com
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