Study did not achieve its primary endpoint in first-of-its
kind trial for patients suffering from life-threatening seizure
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 reported top-line results from its
Phase 3 STATUS Trial of brexanolone (SAGE-547) in the treatment
super-refractory status epilepticus (SRSE). The study did not meet the
primary endpoint, comparing success in weaning of third-line agents and
resolution of potentially life-threatening status epilepticus with
brexanolone vs. placebo (43.9% vs 42.4%; p=0.8775) when added to
Demographics and baseline characteristics were well-balanced between
treatment groups in the study.Due to the severity and complexity of
their underlying medical conditions, serious adverse events commonly
occur in patients with SRSE and were similar in frequency and type
between the two treatment groups. SRSE, a life-threatening persistent
state of seizure that does not respond to first-, second- or third-line
treatments, is a neurological emergency that may cause death or
life-altering outcomes. There are no treatments for SRSE currently
approved by the U.S. Food and Drug Administration (FDA).
Im proud of the Sage team for the significant progress they have made
in improving our understanding of how to best treat these critically ill
patients, said Jeff Jonas, M.D., Chief Executive Officer of Sage. SRSE
is a complicated condition that is poorly understood, and I want to
thank the patients, their families, and the investigators who
participated in the STATUS Trial. Although we did not meet the primary
endpoint, this first-ever trial in a highly variable and complex patient
population confirms that research in a critical care unit is possible
and deepens our understanding of GABA mechanisms and their effect on
brain circuitry. As we continue examining data from the STATUS Trial in
the coming weeks, Im hopeful this information will inform current
treatments, and aid in the development of future treatments for patients
The STATUS Trial was conducted under a Special Protocol Assessment (SPA)
agreement with the FDA and was designed to evaluate the efficacy and
safety of brexanolone in patients with SRSE, ages two years or older, in
the U.S., Canada and Europe. In the double-blind trial, 132 patients
were randomized 1:1 to receive either brexanolone or placebo in addition
to standard-of-care third-line anti-seizure agents for six days.
Patients who failed to respond to brexanolone or placebo were
subsequently eligible for an open-label infusion of brexanolone at a
higher dose over a 6-day period.
SRSE is an extremely complicated condition to treat and there is a
significant unmet need for new treatments, said Eric Rosenthal, M.D.,
co-Principal Investigator of the STATUS Trial, Associate Director of the
Neurosciences Intensive Care Unit and faculty member of the Epilepsy
Service at Massachusetts General Hospital. We have learned a great deal
from the STATUS Trial and while I share the disappointment of patients
and their families who participated in the trial, the STATUS Trial
represents a significant contribution to SRSE research and I hope these
data will provide a foundation for development of future treatments for
patients with this devastating condition.
Summary of Top-line Brexanolone Phase 3 STATUS Trial Results
The study did not meet the primary endpoint of the trial, with 43.9
percent of patients treated with brexanolone versus 42.4 percent of
patients treated with placebo (p=0.8775) successfully weaned from
third-line agents during the double-blind period, and remaining free
of status epilepticus activity for at least the 24 hours following the
end of treatment without the need to reinstate the third-line agents.
Secondary endpoint results were consistent with the primary endpoint.
Approximately 37 percent of patients treated with open-label
brexanolone after the end of the double-blind period achieved
Demographics and baseline characteristics were well-balanced between
patients randomized to brexanolone and placebo.
Consistent with the severity and complexity of SRSE, patients'
underlying conditions, and ongoing ICU treatment nearly all patients
experienced adverse events.
Serious adverse events were similar between the two treatment groups.
The rate of death was similar in the brexanolone and placebo groups.
The rate of adverse events leading to discontinuation of study drug
was similar in the brexanolone and placebo groups and was low overall.
Sage intends to present detailed results from the STATUS Trial at an
upcoming medical meeting.
Conference Call Information
Sage will host a conference call
and webcast today at 7:30 AM ET to discuss the top-line results from its
Phase 3 STATUS Trial of brexanolone in SRSE. 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 conference ID
84426351. 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 Super-Refractory Status Epilepticus
(SE) is an acute medical emergency of persistent, unremitting seizure
lasting greater than five minutes. An SE patient is first treated with
benzodiazepines, and if no response, is then treated with other,
second-line, anti-seizure drugs. If the seizure persists after the
second-line therapy, the patient is diagnosed as having refractory SE
(RSE), admitted to the ICU and placed into a medically induced coma.
Physicians typically use anesthetic agents to induce the coma, along
with antiepileptic drugs in an attempt to stop the ongoing seizure, in
RSE patients. After a period of 24 hours, an attempt is made to wean the
patient from the anesthetic agents to evaluate whether or not the
seizure condition has resolved. Unfortunately, not all patients respond
to weaning attempts, in which case the patient must be maintained in the
medically induced coma. At this point, the patient is diagnosed as
having SRSE. Sage estimates that there are between 25,000 and 41,000
cases of SRSE in the U.S. each year. Currently, there are no therapies
specifically approved for SRSE.
About the STATUS Trial
Sage designed the pivotal Phase 3
STATUS Trial to evaluate the efficacy and safety of brexanolone in
patients with SRSE, ages two years or older, in the U.S., Canada and
Europe. In the double-blind trial, 132 patients were randomized 1:1 to
receive either brexanolone or placebo in addition to standard-of-care
third-line anti-seizure agents for six days. The primary endpoint
compared success in weaning of third-line agents and resolution of
status epilepticus with brexanolone vs. placebo prior to
completion of study treatment and continuing during 24 hours after
completion of study treatment without the need to reinstate the
third-line agents. The STATUS Trial was conducted under a Special
Protocol Assessment (SPA) agreement with the FDA.
About Brexanolone (SAGE-547)
Brexanolone is an allosteric
modulator of both synaptic and extrasynaptic GABAAreceptors.
Brexanolone is an intravenous agent that was evaluated as an adjunctive
therapy for the treatment of super-refractory status epilepticus (SRSE)
in the global Phase 3 STATUS Trial. Brexanolone has been granted both
Fast Track and orphan drug designations by theFDAfor the treatment of
Brexanolone is also being developed for the treatment of postpartum
depression (PPD) and has been granted Breakthrough Therapy designation
by theFDA and PRIority MEdicines (PRIME) designation from theEuropean
Medicines Agency(EMA) in PPD. Sage is currently evaluating brexanolone
in a Phase 3 development program for the treatment of PPD. For more
information about these trials, please visithttps://thehummingbirdstudy.com/.
About Sage Therapeutics
Sage Therapeuticsis 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) completed a Phase 3 trial
for super-refractory status epilepticus, a rare and severe seizure
disorder, and is in Phase 3 clinical development for postpartum
depression. Sage is developing its next generation modulators, including
SAGE-217 and SAGE-718, in various CNS disorders. For more information,
Various statements in this release concern Sage's future
expectations, plans and prospects, including without limitation: our
expectations regarding the development of our product candidates and
their potential in the treatment of various CNS disorders.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 be able to generate
supportive non-clinical or clinical data sufficient to continue clinical
development 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; we may experience delays in
enrollment of our clinical trials or the need for additional data;
decisions or actions of regulatory agencies may affect the timing of our
clinical trials or future regulatory submissions, and regulatory
authorities may not agree with our interpretation of the results of our
non-clinical and clinical studies, and may make decisions that
negatively impact our ability to continue development or to gain
approval, including the risk that regulatory authorities may, despite
prior advice, decide that the clinical and non-clinical data from a
development program are not sufficient to support approval; we may
encounter unexpected adverse events or other safety issues related to
any of our product candidates that may impact further development or our
chances of obtaining regulatory approval; and we mayencounter technical
and other unexpected hurdles in the development and manufacture of our
product candidates which may delay our timing or increase our expenses,
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 theSecurities 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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170912005509/en/
Suda Communications LLC
Maureen L. Suda,
Source: Sage Therapeutics