Therapeutics, a biopharmaceutical company developing novel medicines
to treat life-threatening and rare central nervous system (CNS)
disorders, today announced dose initiation of the first patient in a
Phase 1/2 clinical trial of SAGE-547, a neuroactive steroid, in
super-refractory status epilepticus (SRSE), a critical condition in
which the brain is in a state of persistent seizure. The trial is
designed to evaluate the safety, tolerability and efficacy of SAGE-547
as an adjunctive therapy for the treatment of SRSE.
"Status epilepticus is a serious condition for which there are limited
treatment options. Of the many patients whose condition escalates to
refractory or super-refractory status epilepticus, most will not survive
or will be discharged from the hospital with significant morbidities,"
said Stephen Kanes, M.D., Ph.D., chief medical officer of SAGE
Therapeutics. "SAGE-547 is supported by strong preclinical data and
scientific rationale, and we believe this compound has the potential to
reduce or eliminate seizures in these patients who have exhausted all
other therapeutic options."
This Phase 1/2 trial is an open label study of SAGE-547 as adjunctive
therapy in people with SRSE. The trial is expected to enroll 10 to 15
adult patients with SRSE who have not responded to conventional therapy
with continuous intravenous antiepileptic agents and who remain in a
state of persistent seizure following one or more weaning attempts from
anesthesia. The trial is designed to provide clear data around safety,
exposure and the ability of SAGE-547 to effectivly halt SRSE.
Electrical brain activity will be evaluated via continuous
electroencephalogram (EEG) monitoring before, during and after treatment
with SAGE-547. Patients will be administered SAGE-547 intravenously for
five days while weaning from anesthesia is attempted and will be
monitored for four weeks following treatment.
"This clinical trial exemplifies SAGE's approach to designing studies
with well-defined endpoints and development pathways that we believe
allow us to make highly informed decisions regarding whether to continue
development of our product candidates in an accelerated timeframe," said
Jeffrey Jonas, M.D., chief executive officer of SAGE Therapeutics. "Our
science and chemistry capabilities are targeting the creation of
medicines to treat SE at various stages, and we believe SAGE-547 will be
the first of several product candidates for the treatment of seizure
disorders. We look forward to further evaluating SAGE-547 for the
treatment of this critical and difficult-to-treat CNS condition."
SAGE-547 is a potent positive allosteric modulator of both synaptic and
extra-synaptic GABAA receptors. GABAA receptors
are primary inhibitory neurotransmitters and widely regarded as
validated drug targets for a variety of CNS disorders; however,
traditional approaches of inhibiting or activating the GABA pathway via
synaptic sites only have been associated with significant toxicities.
SAGE-547, developed by SAGE Therapeutics using its proprietary chemistry
platform, has been shown to modulate both synaptic and extrasynaptic GABAA
receptors with high potency and efficacy, and data generated to
date show that SAGE-547 has a unique anticonvulsive role in the
treatment of status epilepticus.
About Status Epilepticus
Status Epilepticus (SE) is an acute, life-threatening seizure condition
that occurs in approximately 150,000 people each year in the U.S.,1
with a mortality rate of nearly 15%. Refractory SE (RSE) occurs in
approximately one-third of SE patients for which first and second line
treatment options are not effective. These patients are moved to an ICU
setting with few treatment options. Currently, there are no approved
therapies for RSE. RSE patients that have become refractory to third
line therapy and remain in status epilepticus despite continuous
intravenous anti-epileptic agents are considered to be in a state of
SRSE. Currently, there are no approved therapies for SRSE.
About SAGE Therapeutics
SAGE Therapeutics is a neuroscience-focused company developing medicines
to treat life-threatening rare CNS disorders. SAGE's lead program,
SAGE-547, is in clinical development for SRSE and is the first of many
compounds the company is developing in its portfolio of potential
seizure medicines. SAGE's robust chemistry platform has generated
multiple new compounds that target the GABAA and NMDA
receptors, which have demonstrated preclinical activity. SAGE
Therapeutics is a private company launched in 2010 by an experienced
team of R&D leaders, CNS experts and investors. For more information,
please visit www.sagerx.com.
1 DeLorenzo, Robert J., Pellock, John M., Towne, Alan R.,
Boggs, Jane G. Epidemiology of Status Epilepticus. J Clin Neuro
1995; 12(4): 316-325.
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