CAMBRIDGE, Mass., Aug. 17, 2015 (GLOBE NEWSWIRE) -- SAGE Therapeutics (NASDAQ:SAGE) today announced it has treated the first patient enrolled in the STATUS Trial (SAGE-547 Treatment as Adjunctive Therapy Utilized in Status Epilepticus), a global, Phase 3, randomized, double-blind, placebo-controlled clinical trial to evaluate SAGE-547 as a treatment for patients with super-refractory status epilepticus (SRSE). SRSE is a rare, life-threatening condition of persistent, unremitting seizure, for which there are no approved therapies.
"The treatment of our first patient in the Phase 3 STATUS Trial, following the rapid advancement of SAGE-547 into Phase 3 development, is an important milestone for the Company, the SAGE-547 program and, most importantly, for patients with SRSE," said Jeff Jonas, M.D., chief executive officer of SAGE Therapeutics. "With our STATUS Trial substantially de-risked through our FDA-agreed Special Protocol Assessment and our first two second-generation molecules planned to enter Phase 1 development this year, we believe SAGE is well-positioned to create significant value as an organization and to make an important difference for patients affected by life-altering central nervous system disorders."
The STATUS Trial is designed to assess the efficacy and safety of SAGE-547 in approximately 126 patients with SRSE, aged two years or older, and will be conducted in the U.S., Canada and Europe. Patients will be randomized 1:1 to receive either SAGE-547 or placebo in addition to standard-of-care third-line anti-seizure agents for six days. The planned primary endpoint of the Phase 3 clinical trial will be successful resolution of status epilepticus (SE) after weaning the patient off all third-line agents, and SAGE-547 or placebo, without resumption of SE within 24 hours after completion of blinded SAGE-547 or placebo administration.
SAGE recently announced that agreement has been reached with the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment on the trial design, endpoints and statistical approach of the Phase 3 clinical trial. The SPA provides agreement from the FDA that the Phase 3 STATUS Trial can adequately address objectives in support of a U.S. regulatory submission for approval of SAGE-547 for the treatment of patients with SRSE.
"As the largest prospective placebo-controlled trial ever conducted in SRSE, the STATUS Trial is an important clinical study," said Stephen Kanes, M.D., Ph.D., chief medical officer of SAGE Therapeutics. "The STATUS Trial is uniquely designed to evaluate SAGE-547's efficacy and safety as an interventional, adjunctive therapy compared to standard of care over a six day treatment period, and will allow patients that fail blinded treatment to be treated with an open-label, higher dose regimen of SAGE-547. I would like to thank the trial sites and investigators for participating in this important trial seeking to address the significant unmet need faced by these critically ill patients and their families."
SAGE's Phase 3 open-label expanded access protocol, designated Study 302, was initiated in April 2015 and continues its enrollment. Study 302 is designed to make SAGE-547 available to patients in the U.S. who are affected by SRSE and who have not been admitted to, nor can be transferred to, a planned STATUS Trial clinical site.
In a completed Phase 1/2 open-label clinical trial, SAGE-547 demonstrated robust activity, with a 77 percent response rate in 22 evaluable patients with SRSE, and also a favorable tolerability profile. Independent of treatment response, six patient deaths occurred within the trial period, all driven by underlying conditions. Although 64 percent of patients reported serious adverse events, none were drug-related as determined by the Safety Review Committee.
SAGE-547 is an allosteric modulator of both synaptic and extra-synaptic GABAA receptors. SAGE-547 is an intravenous agent in Phase 3 clinical development as an adjunctive therapy for the treatment of super-refractory status epilepticus (SRSE). SAGE-547 has been granted both Fast Track and orphan drug designations by the U.S. Food and Drug Administration (FDA) for the treatment of SRSE. The active pharmaceutical ingredient has been contributed under agreement by the Regents of the University of California and the University of California, Davis.
About Status Epilepticus
Status epilepticus (SE) is a life-threatening seizure condition that occurs in approximately 150,000 people each year in the U.S., of which 30,000 SE patients die.1 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.
Currently, there are no therapies that have been specifically approved for RSE; however, physicians typically use anesthetic agents to induce the coma and stop the seizure immediately. 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. We estimate that there are 25,000 cases of SRSE in the U.S.1-3 each year. Currently, there are no therapies specifically approved for SRSE.
About SAGE Therapeutics
SAGE Therapeutics is a clinical-stage biopharmaceutical company committed to developing and commercializing novel medicines to treat life-altering central nervous system (CNS) disorders. SAGE's lead program, SAGE-547, is in Phase 3 clinical development for super-refractory status epilepticus (SRSE) and is the first of several compounds the Company is developing in its portfolio of potential CNS medicines. SAGE's proprietary chemistry platform has generated multiple new compounds that target GABAA and NMDA receptors, which are broadly accepted as impacting many psychiatric and neurological disorders. For more information, please visit www.sagerx.com.
Various statements in this release concerning SAGE's future expectations, plans and prospects, including without limitation, SAGE's expectations regarding SAGE-547 as a treatment for SRSE, essential tremor and postpartum depression, statements concerning the potential safety and efficacy of SAGE-547 and durability of response, the potential importance and impact of the Phase 3 STATUS trial and the open-label expanded access protocol for SAGE-547, whether the results from the Phase 3 STATUS trial together with other available clinical data for SAGE-547 will be sufficient to support submission of an NDA for this product candidate, and the timing of SAGE's clinical trials for its product candidates constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. In particular, it should be noted that there is limited data concerning the safety and efficacy of SAGE-547. These data may not be repeated or observed in ongoing or future trials involving SAGE-547 or SAGE's other product candidates. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, SAGE's ability to successfully demonstrate the efficacy and safety of its drug candidates, the pre-clinical and clinical results for its product candidates, which may not support further development of product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials, obtaining, maintaining and protecting intellectual property, SAGE's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, competition from others developing products for similar uses, SAGE's ability to manage operating expenses, SAGE's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, SAGE's dependence on third parties for development, manufacture, marketing, sales and distribution of products, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in SAGE's most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in SAGE's subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent SAGE's views only as of today and should not be relied upon as representing its views as of any subsequent date. SAGE explicitly disclaims any obligation to update any forward-looking statements.
1 DeLorenzo RJ, Pellock JM, Towne AR, Boggs JG. J Clin Neuro 1995; 12(4): 316-325.
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3 Novy J, Logroscino G, Rossetti AO. Epilepsia 2010; 51(2): 251-256.