CAMBRIDGE, Mass.--(BUSINESS WIRE)--Sage Therapeutics (NASDAQ: SAGE), a clinical-stage biopharmaceutical company developing novel medicines to treat life-altering central nervous system (CNS) disorders, today announced its expedited development plan for SAGE-217 following a Breakthrough Therapy meeting with the U.S. Food and Drug Administration (FDA). This development plan is intended to support a potential filing for approval of SAGE-217 in the U.S. for the treatment of major depressive disorder (MDD) and postpartum depression (PPD).
The expedited development plan for SAGE-217 includes a single additional placebo-controlled Phase 3 pivotal trial in patients with MDD and the ongoing placebo-controlled trial in women with PPD, now designated a pivotal trial. Both clinical trials are designed to evaluate the novel concept of episodic dosing, or short course treatment, with SAGE-217 and its effect on the reduction of depressive symptoms compared to placebo. An open-label study will evaluate the potential of episodic treatment for recurrent or new major depressive episodes and provide additional safety data.
Sage plans to initiate the placebo-controlled Phase 3 trial in MDD during the second half of 2018. Further, Sage anticipates announcing top-line data from the placebo-controlled pivotal trial of SAGE-217 in PPD in the fourth quarter of 2018. This expedited pivotal program is supported by the results of a positive placebo-controlled trial in patients with MDD announced in December 2017.
“Sage is excited to receive feedback from the FDA that provides a possible groundbreaking path forward for the development of SAGE-217 for the treatment of depression,” said Jeff Jonas, M.D., chief executive officer of Sage. “In this development program, we are exploring the potential for patients with MDD to feel well within days, with just a 2-week course of treatment – similar to how antibiotics are used today – instead of enduring long-term chronic treatment. We believe a medicine with rapid onset and robust response could be truly paradigm shifting. SAGE-217, if successfully developed and approved, may rewrite the textbook on how the tens of millions of people suffering from MDD are treated, ultimately turning depression into a disorder, not an identity.”
Incorporating feedback from the FDA, the following are the elements of the expected clinical and regulatory path for the SAGE-217 development program moving forward:
- Support from the FDA on a path forward in both MDD and PPD, allowing an expedited development plan.
- Ongoing multi-center, double-blind, placebo-controlled, randomized clinical trial evaluating two weeks of 30mg SAGE-217 treatment compared to placebo in 140 patients with PPD, confirmed as appropriate to support registration for PPD, if both the MDD and PPD trial are successful, and is now designated a pivotal clinical trial.
- One additional Phase 3 placebo-controlled efficacy study planned for SAGE-217 in MDD, evaluating two weeks of 20mg or 30mg SAGE-217 treatment compared to placebo in 450 patients with MDD, with four weeks of additional follow-up.
- Support from FDA in exploring the novel concept of episodic dosing.
- Additional data regarding patient safety and potential treatment of recurrent or new major depressive episodes will be acquired through a long-term open-label study program in which approximately 300 patients will be followed for six months and 100 patients would be followed for a year after initial treatment and episodic retreatment as needed.
Sage received Breakthrough Therapy Designation from the FDA for SAGE-217 in MDD in February 2018. The Breakthrough Therapy Designation is intended to offer a potentially expedited development path and review for promising drug candidates, which includes increased interaction and guidance from the FDA. This regulatory decision was based primarily on the positive results from the placebo-controlled trial of SAGE-217 in 89 adult patients with moderate to severe MDD. In the trial, SAGE-217 met the primary endpoint with a statistically significant mean reduction in the Hamilton Rating Scale for Depression (HAM-D) 17-item total score from baseline at Day 15 in the SAGE-217 group, compared to placebo (p<0.0001). Statistically significant improvements were observed in the HAM-D score compared to placebo by the morning following the first dose through Week 4 and the effects of SAGE-217 remained numerically greater than placebo through the end of follow-up at Week 6. SAGE-217 was generally well-tolerated. The most common adverse events in the SAGE-217 group were headache, dizziness, nausea, and somnolence.
Conference Call Information
Sage will host a conference call
and webcast today at 8:00 A.M. ET to discuss the expedited development
plan for SAGE-217 following a Breakthrough Therapy meeting with the U.S.
Food and Drug Administration (FDA). 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 866-450-8683 (toll-free
domestic) or 281-542-4847 (international) and use the conference ID
6378326. 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 FDA Breakthrough Therapy Designation
The FDA's
Breakthrough Therapy Designation is intended to expedite the development
and review of a drug candidate that is planned for use, alone or in
combination with one or more other drugs, to treat a serious or
life-threatening disease or condition when preliminary clinical evidence
indicates that the drug may demonstrate substantial improvement over
existing therapies on one or more clinically significant endpoints. The
benefits of Breakthrough Therapy Designation include the same benefits
as Fast Track Designation, plus an organizational commitment involving
FDA’s senior managers with more intensive guidance from the FDA.
Breakthrough Therapy Designation does not change the standards for
approval.
About Major Depressive Disorder
Major depressive disorder
(MDD) is a common but serious mood disorder in which patients exhibit
depressive symptoms, such as a depressed mood or a loss of interest or
pleasure in daily activities consistently for at least a two-week
period, and demonstrate impaired social, occupational, educational or
other important functioning. It is estimated that approximately 16
million people in the U.S. suffer from MDD each year. While
antidepressants are widely used for treatment, large scale studies have
demonstrated the need for additional therapies.
About Postpartum Depression
Postpartum depression (PPD) is a
distinct and readily identified major depressive disorder that is the
most common medical complication of childbirth, affecting a subset of
women typically commencing in the third trimester of pregnancy or within
the months after giving birth. PPD may have devastating consequences for
a woman and for her family, which may include significant functional
impairment, depressed mood and/or loss of interest in her newborn, and
associated symptoms of depression such as loss of appetite, difficulty
sleeping, motor challenges, lack of concentration, loss of energy and
poor self-esteem. Suicide is the leading cause of maternal death
following childbirth. In the U.S., estimates of new mothers identified
with PPD each year vary by state from 8 to 20 percent, with an overall
average of 11.5 percent. More than half of these cases may go
undiagnosed without proper screening. There are no FDA-approved
therapies for PPD and there is a high unmet medical need for improved
pharmacological therapy in PPD.
About SAGE-217
SAGE-217 is a next generation positive
allosteric modulator that has been optimized for selectivity to synaptic
and extrasynaptic GABAA receptors and a pharmacokinetic
profile intended for daily oral dosing. The GABA system is the major
inhibitory signaling pathway of the brain and CNS, and contributes
significantly to regulating CNS function. SAGE-217 is currently being
developed for MDD and certain other mood and movement disorders.
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, GABAA and
NMDA. Sage's lead program, a proprietary IV formulation of brexanolone
(SAGE-547), has completed Phase 3 clinical development for postpartum
depression and a new drug application is currently under review with the
U.S. Food and Drug Administration. 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 statements as to the potential for
expedited development of SAGE-217 in MDD and PPD; our expectations as to
the timing of results from the clinical trial of SAGE-217 in PPD and
initiation of a Phase 3 clinical trial of SAGE-217 in MDD; our
expectations regarding the potential sufficiency of the planned
development program, if successful, to support regulatory filing and
approval of SAGE-217 in MDD and PPD; our views as to the need for
additional treatment options in MDD and the potential of SAGE-217 to
represent a potential paradigm shift in the treatment of MDD; our
estimates as to the number of patients with MDD and PPD; our statements
regarding the potential for expedited development and review as the
result of Breakthrough Therapy Designation; and our statements regarding
the potential of SAGE-217 and Sage's other product candidates. 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 not achieve expedited
development or review of SAGE-217 despite the results of the
Breakthrough Therapy meeting; the FDA may ultimately decide that the
design or results of our clinical trials for SAGE-217 are not sufficient
for regulatory approval in MDD, PPD or any other indication or do not
support episodic treatment of MDD which is the focus of our expedited
development plan; we may encounter delays in enrollment and site
initiation that may impact our ability to meet our expected time-lines;
we may not be successful in our development of SAGE-217 in MDD or PPD or
in our development of any of our product candidates in any indication we
are currently pursuing or may in the future pursue; success in our
non-clinical studies or in earlier stage clinical trials may not be
repeated or observed in ongoing or future studies, and ongoing and
future non-clinical and clinical results, including with respect to
SAGE-217, may not support further development or be sufficient to gain
regulatory approval to market the product; we may encounter adverse
events at any stage of development that negatively impact further
development; the actual size of the MDD and PPD patient populations may
be significantly lower than our estimates and, even if SAGE-217 is
approved, it may only be approved or used to treat a subset of the
relevant patient populations; and we may encounter technical and other
unexpected hurdles in the development and manufacture of SAGE-217 or any
of our other products which may delay our timing or change our plans, 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.