Phase 3 STATUS Trial of brexanolone in SRSE
nearing completion of enrollment – expects top-line results in Q3
2017
Advancing SAGE-217 into Part B open-label Phase
2 trial in Parkinson’s disease based on initial activity signal
First patient dosed in placebo-controlled Phase
2 clinical trial of SAGE-217 in major depressive disorder
Conference call today at 4:30 PM ET
Sage Therapeutics, Inc. (NASDAQ:SAGE), a clinical-stage
biopharmaceutical company developing novel medicines to treat
life-altering central nervous system (CNS) disorders, today
reported business highlights and financial results for the first
quarter ended March 31, 2017.
“We continue to make good progress in building Sage into a
leading CNS company with the potential to deliver differentiated
medicines for a variety of central nervous system disorders. We are
focused on closing the innovation gap in areas of brain disorders
where more breakthroughs for patients are needed,” said Jeff Jonas,
M.D., Chief Executive Officer of Sage. “We are now nearing
completion of enrollment in our lead Phase 3 program in
super-refractory status epilepticus (SRSE), and remain focused on
completing Phase 3 clinical development of brexanolone in both SRSE
and postpartum depression (PPD) in 2017. Further, we continue to
advance our growing pipeline of novel product candidates, including
our lead oral compound, SAGE-217, in four clinical programs in both
mood and movement disorders.”
Brexanolone in SRSE - Phase 3 STATUS
Trial Update
Sage is nearing completion of enrollment in the Phase 3 STATUS
Trial, the first ever global, randomized, double-blind,
placebo-controlled trial in SRSE. The Company expects to report
top-line results from the STATUS Trial in the third quarter of 2017
after enrollment of an anticipated 126 evaluable patients and
completion of all study follow-up periods and data analysis. Sage
expects top-line results to include the primary endpoint, safety
and tolerability, and select secondary endpoints, including
open-label retreatment arm response and the Clinical Global
Impression scale.
Top-Line Results from Part A of
SAGE-217 Phase 2 in Parkinson’s Disease
Sage today announced top-line results from the Part A open-label
portion of a Phase 2 clinical trial of SAGE-217 in Parkinson's
disease:
- SAGE-217 was studied in an exploratory
open-label trial designed to understand the safety, tolerability,
pharmacokinetics and activity of SAGE-217 in a cohort of 12
Parkinson’s disease patients in order to determine whether there is
a suitable activity signal to justify further development, and if
so, to help develop the methodology needed to expedite progress
into further Phase 2 testing.
- Twelve Parkinson’s disease patients
with moderate disease severity (Hoehn and Yahr stage 2 or 3) who
were on stable doses of the anti-Parkinsonian agent
levodopa/carbidopa prior to the study were evaluated. As an
exploratory study, the Part A phase enrolled an all-comer
population that was not enriched based on tremor severity or for
any other particular Parkinson’s disease symptom complex. Patients
were withdrawn from maintenance therapy and administered their
baseline medicine (levodopa/carbidopa morning dose only) for three
days, followed by a single morning dose of SAGE-217 administered as
a monotherapy for the subsequent four days.
- For the overall population in the
trial, levodopa/carbidopa activity was primarily focused on the
motor symptoms of bradykinesia and rigidity, while SAGE-217
activity as a monotherapy was primarily focused on tremor
symptoms.
- In the five subjects with overt tremor
(tremor score over five at baseline), an approximate 20-30%
improvement in tremor symptoms was observed on the four days of
SAGE-217 open-label treatment, as assessed by change in the
Movement Disorder Society-Unified Parkinson’s Disease Rating Scale
(MDS-UPDRS) Part III tremor score. This improvement in tremor score
during the SAGE-217 dosing phase was longer-lasting than the effect
on tremor observed in these subjects during the
levodopa/carbidopa-only phase.
- Administration of SAGE-217 during the
day was found to be generally well-tolerated with no serious
adverse events or discontinuations reported. Similar to findings in
the Phase 1 clinical program, the most common adverse events were
sedation and somnolence (occurring 2 to 4 hours post dose). While
dosing was initiated at the 30 mg per day maximum tolerated dose
established in the Phase 1 program, the majority of patients were
down-titrated to 10 to 20 mg of SAGE-217 per day.
- Based on the signal of activity in
reducing Parkinsonian tremor in these patients, Sage plans to
proceed to an open-label Part B study evaluating SAGE-217 as an
adjunctive treatment to anti-Parkinsonian agents in
tremor-predominant patients, and intends to further evaluate
non-motor symptoms of Parkinson’s disease, including depression,
anxiety, cognition and sleep.
Pipeline Update
Sage is advancing a portfolio of novel central nervous system
(CNS) product candidates targeting the GABA and NMDA receptor
systems. Dysfunction in these systems is known to be at the core of
numerous psychiatric and neurological disorders. Sage is pursuing a
data-driven approach to CNS drug development by employing efficient
human proof-of-concept studies both to uncover activity signals and
to help understand future trial methodology, before investing in
larger clinical programs.
- Brexanolone (SAGE-547): Sage is
currently developing brexanolone in separate Phase 3 clinical
programs as an acute interventional treatment for super-refractory
status epilepticus (SRSE) and postpartum depression (PPD).
Brexanolone is Sage’s proprietary intravenous (IV) formulation of
allopregnanolone, a naturally occurring neuroactive steroid that
acts as a synaptic and extrasynaptic modulator of the GABAA
receptor.
- SRSE: Sage is evaluating
brexanolone in the Phase 3 STATUS Trial, a global, randomized,
double-blind, placebo-controlled trial, designed to evaluate
brexanolone as a potential adjunctive therapy for SRSE, a
life-altering and persistent seizure condition with no treatments
currently approved by the U.S. Food and Drug Administration (FDA).
The Phase 3 clinical program is being conducted in agreement with
the FDA under a Special Protocol Assessment (SPA). Sage has also
received positive scientific advice from the European Medicines
Agency (EMA) with respect to development of brexanolone for SRSE.
Based on this advice, the Company believes the Phase 3 clinical
program, if successful, will be sufficient to support submission of
a marketing authorization application (MAA) to the EMA seeking
approval of brexanolone for SRSE in the EU.
- PPD: Sage is currently
enrolling its Phase 3 clinical program evaluating brexanolone as a
potential treatment for PPD, consisting of separate
placebo-controlled trials in severe PPD patients (202B) and in
moderate PPD patients (202C), collectively known as the Hummingbird
Study. In 2016, the FDA granted Breakthrough Therapy Designation
and the EMA granted PRIority MEdicines (PRIME) designation to
brexanolone for the treatment of PPD. Sage recently conducted its
PRIME meeting with EMA authorities, and is now in process of
seeking formal scientific advice. Sage expects to report top-line
results from the Phase 3 clinical trials of brexanolone in PPD in
the second half of 2017.
- SAGE-217: Sage’s most
advanced, next-generation product candidate is SAGE-217, a novel,
orally-active neuroactive steroid that, like brexanolone, is a
positive allosteric modulator of synaptic and extrasynaptic GABAA
receptors. SAGE-217 is currently in Phase 2 development in both
mood and movement disorders, with four Phase 2 clinical programs
now underway.
- Mood Disorders:
- Major Depressive Disorder
(MDD): Sage recently initiated dosing of patients in the
Part B randomized, double-blind, placebo-controlled Phase 2
clinical trial of SAGE-217 in MDD. Earlier this year, Sage reported
positive clinical results from the open-label Part A portion of the
Phase 2 clinical program evaluating SAGE-217 in patients with
moderate to severe MDD. The Part B study is expected to evaluate up
to 66 patients with moderate to severe MDD for two weeks of
treatment with SAGE-217 compared to placebo. Top-line results from
the Part B study are expected in the first half of 2018.
- PPD: Sage is currently
enrolling a Phase 2 clinical trial of SAGE-217 in PPD. The Phase 2
multi-center, double-blind, placebo-controlled, randomized trial
will evaluate the efficacy, safety, tolerability, and
pharmacokinetics of SAGE-217 in the treatment of patients with
severe PPD. Top-line results from the SAGE-217 PPD study are
expected in the second half of 2017.
- Movement Disorders:
- Essential tremor: Sage is
currently enrolling its Phase 2 clinical trial of SAGE-217 in
essential tremor. The efficacy, safety, tolerability, and
pharmacokinetics of SAGE-217 are being evaluated in a Phase 2
multi-center, double-blind, placebo-controlled, randomized
withdrawal trial in the treatment of patients with essential
tremor. Top-line results from the SAGE-217 essential tremor study
are expected in the second half of 2017.
- Parkinson's disease: Based
on a positive activity signal observed in the Part A open-label
portion of the Phase 2 program of SAGE-217 in Parkinson's disease,
Sage is planning to initiate an open-label Part B study to evaluate
SAGE-217 as an adjunctive treatment in tremor-predominant
Parkinson's disease patients. The Part B study is expected to be
initiated in the first half of 2017 with top-line results
anticipated in the second half of 2017.
- Other GABA Programs: Sage is
currently evaluating a series of novel GABAA receptor modulators in
pre-clinical development, including SAGE-324, a novel,
orally-active next-generation positive allosteric modulator of
synaptic and extrasynaptic GABAA receptors. SAGE-324 is currently
in IND-enabling studies, and is intended to be developed with a
focus on orphan epilepsies and indications involving GABA
hypofunction.
- NMDA Programs: Sage is also
developing novel compounds that target the NMDA receptor. The first
product candidate selected for development from this program is
SAGE-718, a novel, oral, first-in-class oxysterol-based positive
allosteric modulator of the NMDA receptor. Sage recently initiated
Phase 1 clinical development of SAGE-718, and expects top-line
results from a Phase 1 single ascending dose (SAD) trial of
SAGE-718 in healthy volunteers in the second half of 2017. Positive
modulation of NMDA receptors may have potential in the treatment of
a range of neurological disorders associated with a variety of
cognitive, neurological and behavioral symptoms.
Expected Near-Term Clinical
Milestones
- Trial Initiations:
- Part B of Phase 2 trial of SAGE-217 in
Parkinson’s disease (1H 2017)
- Top-Line Data Readouts:
- Phase 3 STATUS Trial of brexanolone in
SRSE (Q3 2017)
- Phase 3 Hummingbird Study (202B) of
brexanolone in PPD (2H 2017)
- Phase 3 Hummingbird Study (202C) of
brexanolone in PPD (2H 2017)
- Phase 2 trial of SAGE-217 in essential
tremor (2H 2017)
- Phase 2 trial of SAGE-217 in PPD (2H
2017)
- Part B of Phase 2 trial of SAGE-217 in
Parkinson’s disease (2H 2017)
- Phase 1 single-ascending dose (SAD)
trial of SAGE-718 (2H 2017)
- Part B of Phase 2 trial of SAGE-217 in
MDD (1H 2018)
Financial Results for the First Quarter
of 2017
- Cash Position: Cash, cash
equivalents and marketable securities as of March 31, 2017 were
$342.6 million, compared with $397.5 million at December 31,
2016.
- R&D Expenses: Research
and development expenses were $45.2 million, including $3.6 million
of non-cash stock-based compensation expense, in the first quarter
of 2017, compared to $23.6 million, including $1.6 million of
non-cash stock-based compensation expense, for the same period of
2016. The increase in R&D expenses year-over-year was primarily
due to the ongoing clinical development of brexanolone in SRSE and
PPD; the ongoing Phase 2 development of SAGE-217; completion of
IND-enabling studies and preparation for Phase 1 development for
SAGE-718; continuing discovery efforts to identify new development
candidates; and investments in R&D headcount to support the
growth in Sage’s pipeline and operations.
- G&A Expenses: General
and administrative expenses were $12.3 million, including $2.6
million of non-cash stock-based compensation expense, in the first
quarter of 2017, compared to $7.1 million, including $2.1 million
of non-cash stock-based compensation expense, for the same period
of 2016. The increase in G&A expenses year-over-year was
primarily due to the increase in personnel-related expenses,
professional fees, costs related to continued preparations for a
potential commercial launch, and facilities-related costs to
support expanding operations.
- Net Loss: Net loss was
$56.8 million for the first quarter of 2017, compared to a net loss
of $30.5 million for the comparable period of 2016.
- Financial Guidance: Sage expects
that its existing cash, cash equivalents and marketable securities
will fund its anticipated level of operations, based on its current
operating plans, into the second quarter of 2018.
Conference Call
Information
Sage will host a conference call and webcast today at 4:30
PM ET to discuss its first quarter financial results and
recent corporate updates. The live webcast can be accessed on the
investor page of Sage's website at investor.sagerx.com. The
conference call can be accessed by dialing 1-866-450-8683
(toll-free domestic) or 1-281-542-4847 (international) and using
the conference ID 12287678. 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 clinical-stage biopharmaceutical company
committed to developing novel medicines to transform the lives of
patients with life-altering central nervous system (CNS) disorders.
Sage has a portfolio of novel product candidates targeting critical
CNS receptor systems, GABA and NMDA. Sage's lead program,
brexanolone (SAGE-547), is in Phase 3 clinical development for
super-refractory status epilepticus, a rare and severe seizure
disorder, and for postpartum depression. Sage is developing its
next generation modulators, including SAGE-217 and SAGE-718, in
various CNS disorders. 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 expectations regarding development of our product candidates
and their potential in the treatment of various CNS disorders; the
expected timing of initiation and completion of clinical trials;
the anticipated availability and announcement of data and results
from clinical trials of our product candidates; our plans for
evaluation of new indications and new compounds; our expectations
regarding the regulatory pathway for brexanolone (SAGE-547) in the
treatment of SRSE in the EU, and our belief that the results of the
current development program for brexanolone in SRSE, if successful,
will be sufficient for an MAA filing in the EU; our expectations
regarding a potential future new drug application and MAA filing
and commercial launch of brexanolone, if successfully developed and
approved; and our expectations with respect to future cash use and
cash needs. 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 continue to experience slower than expected
enrollment and randomization of evaluable patients in the STATUS
trial or slower than expected clinical site initiation and
enrollment in our other clinical trials, or the potential need for
additional analysis or data or the need to enroll additional
patients, leading to possible delays in completion of trials or in
the availability of data; we may not be able to generate supportive
non-clinical data or to successfully demonstrate the efficacy and
safety of our product candidates at each stage of clinical
development; success in our non-clinical studies or in earlier
stage clinical trials may not be repeated or observed in ongoing or
future studies involving the same compound or other product
candidates, and ongoing and future pre-clinical and clinical
results may not support further development of product candidates
or be sufficient to gain regulatory approval to launch and
commercialize any product; decisions or actions of regulatory
agencies may affect the initiation, timing, progress and cost of
clinical trials, and our ability to proceed with further clinical
studies of a product candidate or to obtain marketing approval or
may result in restrictions in an approved indication or the need
for additional clinical trials, including the risk that the EMA
may, despite scientific advice, decide that the data from our Phase
3 trial in SRSE are not sufficient to support approval; the
internal and external costs required for our activities, and to
build our organization in connection with such activities, and the
resulting use of cash, may be higher than expected, or we may
conduct additional clinical trials or pre-clinical studies, or
engage in new activities, requiring additional expenditures and
using cash more quickly than anticipated; and we may encounter
technical and other unexpected hurdles in the development and
manufacture of our products which may delay our timing or increase
our expenses and use of cash, as well as those risks more fully
discussed in the section entitled "Risk Factors" in our most recent
Annual Report on Form 10-K, 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 Balance
Sheets
(in thousands)
(Unaudited)
March 31, 2017 December 31, 2016 Assets
Current Assets: Cash and cash equivalents $ 145,460 $ 168,517
Marketable securities 197,104 228,962 Prepaid expenses and other
current assets 6,480 5,100 Total current assets
349,044 402,579 Property and equipment and other long-term assets
2,124 1,952 Total assets $ 351,168 $ 404,531
Liabilities and Stockholders'
Equity
Current Liabilities: Accounts payable $ 8,230 $ 12,817 Accrued
expenses 23,652 22,352 Total current liabilities
31,882 35,169 Other liabilities 840 845 Total
liabilities 32,722 36,014 Total stockholders' equity 318,446
368,517 Total liabilities and stockholders' equity $ 351,168
$ 404,531
Sage Therapeutics, Inc. and
Subsidiaries Condensed Consolidated Statements of
Operations
(in thousands, except share and per share
data)
(Unaudited)
Three Months Ended March 31, 2017
2016 Operating expenses: Research and development $ 45,200 $
23,581 General and administrative 12,280 7,133
Total operating expenses 57,480 30,714
Loss from operations (57,480 ) (30,714 ) Interest
income, net 707 175 Other expense, net (5 ) (4 ) Net
loss $ (56,778 ) $ (30,543 ) Net loss per share - basic and diluted
$ (1.52 ) $ (0.97 ) Weighted average shares outstanding - basic and
diluted 37,269,148 31,643,216
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170509006196/en/
Investors:Sage TherapeuticsPaul Cox,
617-299-8377paul.cox@sagerx.comorMedia:Suda Communications
LLCMaureen L. Suda, 585-387-9248maureen.suda@sagerx.com
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